Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Goodman OB, Flaig TW, Molina A, Mulders PFA, Fizazi K, Suttmann H, Li J, Kheoh T, de Bono JS, Scher HI. Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 2014;17:34-9. [PMID: 24080993 PMCID: PMC3921671 DOI: 10.1038/pcan.2013.41] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 07/26/2013] [Accepted: 08/22/2013] [Indexed: 12/11/2022]

For:	Goodman OB, Flaig TW, Molina A, Mulders PFA, Fizazi K, Suttmann H, Li J, Kheoh T, de Bono JS, Scher HI. Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 2014;17:34-9. [PMID: 24080993 PMCID: PMC3921671 DOI: 10.1038/pcan.2013.41] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 07/26/2013] [Accepted: 08/22/2013] [Indexed: 12/11/2022]

Number

Cited by Other Article(s)

Sharifi MN, Feng E, Rydzewski NR, Taylor AK, Sperger JM, Shi Y, Helzer KT, Bootsma ML, Carreno V, Chang AH, Nunamaker LA, Blitzer GC, Shang TA, Subramanian A, Bjartell A, Josefsson A, Wikström P, Feng E, Kohli M, Yang R, Dehm SM, Small EJ, Aggarwal R, Quigley DA, Lang JM, Zhao SG, Sjöström M. Adverse prognosis gene expression patterns in metastatic castration-resistant prostate cancer. Mol Oncol 2025. [PMID: 39985777 DOI: 10.1002/1878-0261.70001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/21/2024] [Accepted: 02/10/2025] [Indexed: 02/24/2025] Open

Affiliation(s)

Marina N Sharifi Carbone Cancer Center, University of Wisconsin-Madison, WI, USA Department of Medicine, University of Wisconsin-Madison, WI, USA
Eric Feng Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Department of Radiation Oncology, University of California, San Francisco, CA, USA
Nicholas R Rydzewski Department of Human Oncology, University of Wisconsin-Madison, WI, USA
Amy K Taylor Carbone Cancer Center, University of Wisconsin-Madison, WI, USA Department of Medicine, University of Wisconsin-Madison, WI, USA
Jamie M Sperger Carbone Cancer Center, University of Wisconsin-Madison, WI, USA Department of Medicine, University of Wisconsin-Madison, WI, USA
Yue Shi Department of Human Oncology, University of Wisconsin-Madison, WI, USA
Kyle T Helzer Department of Human Oncology, University of Wisconsin-Madison, WI, USA
Matthew L Bootsma Department of Human Oncology, University of Wisconsin-Madison, WI, USA
Viridiana Carreno Department of Medicine, University of Wisconsin-Madison, WI, USA
Alex H Chang Department of Medicine, University of Wisconsin-Madison, WI, USA
Luke A Nunamaker Carbone Cancer Center, University of Wisconsin-Madison, WI, USA
Grace C Blitzer Department of Human Oncology, University of Wisconsin-Madison, WI, USA
Tianfu Andy Shang Department of Human Oncology, University of Wisconsin-Madison, WI, USA
Aishwarya Subramanian Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Department of Radiation Oncology, University of California, San Francisco, CA, USA
Anders Bjartell Department of Translational Medicine, Lund University, Malmö, Sweden Department of Urology, Skåne University Hospital, Malmö, Sweden
Andreas Josefsson Department of Diagnostics and Interventions, Urology, Umeå University, Sweden Wallenberg Center for Molecular Medicine, Umeå University, Sweden
Pernilla Wikström Department of Medical Biosciences, Pathology, Umeå University, Sweden
Emily Feng Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Department of Radiation Oncology, University of California, San Francisco, CA, USA
Manish Kohli Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
Rendong Yang Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Scott M Dehm Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA Department of Urology, University of Minnesota, Minneapolis, MN, USA
Eric J Small Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA, USA
Rahul Aggarwal Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA, USA
David A Quigley Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Department of Urology, University of California, San Francisco, CA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
Joshua M Lang Carbone Cancer Center, University of Wisconsin-Madison, WI, USA Department of Medicine, University of Wisconsin-Madison, WI, USA
Shuang G Zhao Carbone Cancer Center, University of Wisconsin-Madison, WI, USA Department of Human Oncology, University of Wisconsin-Madison, WI, USA William S. Middleton Memorial Veterans' Hospital, Madison, WI, USA
Martin Sjöström Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA Department of Radiation Oncology, University of California, San Francisco, CA, USA Division of Oncology, Department of Clinical Sciences Lund, Lund University, Sweden Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden

Collapse

Muniz M, Sartor O, Orme JJ, Koch RM, Rosenow HR, Mahmoud AM, Andrews JR, Kase AM, Riaz IB, Belge Bilgin G, Thorpe MP, Kendi AT, Johnson GB, Ravi P, Kwon ED, Childs DS. Outcomes for Patients with Metastatic Castration-Resistant Prostate Cancer and Liver Metastasis Receiving [¹⁷⁷Lu]Lu-PSMA-617. J Nucl Med 2024;65:1932-1938. [PMID: 39477495 PMCID: PMC11619589 DOI: 10.2967/jnumed.124.268277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 10/02/2024] [Indexed: 12/08/2024] Open

Abstract

It is well known that patients with liver metastasis from metastatic castration-resistant prostate cancer have poor or only transient responses to many forms of systemic therapy. Data on outcomes after treatment with [177Lu]Lu-PSMA-617 (LuPSMA) are scarce. The VISION trial reports a hazard ratio for overall survival (OS) in the subgroup of patients with liver metastasis without disclosing the absolute duration of survival. Using real-world clinical data, we examined this important subgroup of patients, describing prostate-specific antigen (PSA) response and OS. Methods: A single-institution database was assembled to include all patients receiving LuPSMA at Mayo Clinic in Rochester, Minnesota, for whom treatment was initiated between March 2022 and March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were then categorized by presence or absence of liver metastasis on pretreatment prostate-specific membrane antigen (PSMA) PET. PSA response and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ2 testing and the Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Finally, those with pretreatment circulating tumor DNA as determined in an 83-gene panel were assessed for the presence of pathogenic and likely pathogenic alterations. These findings were summarized using descriptive statistics and compared between the 2 cohorts using the Fisher exact test. Results: The overall cohort consisted of 273 patients, including 43 (15.75%) with liver metastasis on pretreatment PSMA PET/CT. The median number of cycles received was 3 (range, 1-6) for patients with liver metastasis and 5 (range, 1-6) for those without hepatic involvement. The 50% or greater reduction in PSA from baseline response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs 49.77% [106/213], P = 0.019). At a median follow-up of 10 mo (interquartile range, 9-13 mo), there was a significant difference in median OS (8.35 mo vs. not reached, P < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; P < 0.001). Conclusion: Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment. Alternative and combination approaches should be explored to maximize the antitumor activity of radiopharmaceutical therapy in the liver.

Collapse

Wenzel M, Hoeh B, Humke C, Koll F, Cano Garcia C, Siech C, Steuber T, Graefen M, Traumann M, Kluth L, Chun FKH, Mandel P. Influence of metastatic sites and burden on oncological outcomes in patients progressing to metastatic castration resistant prostate cancer. World J Urol 2024;42:615. [PMID: 39487858 PMCID: PMC11531415 DOI: 10.1007/s00345-024-05341-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 10/22/2024] [Indexed: 11/04/2024] Open

Abstract

PURPOSE

Metastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients.

METHODS

We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models.

RESULTS

Of 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05).

CONCLUSION

M1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes.

Collapse

Ni X, Wei Y, Li X, Pan J, Fang B, Zhang T, Lu Y, Ye D, Zhu Y. From biology to the clinic - exploring liver metastasis in prostate cancer. Nat Rev Urol 2024;21:593-614. [PMID: 38671281 DOI: 10.1038/s41585-024-00875-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2024] [Indexed: 04/28/2024]

Abstract

Liver metastases from prostate cancer are associated with an aggressive disease course and poor prognosis. Results from autopsy studies indicate a liver metastasis prevalence of up to 25% in patients with advanced prostate cancer. Population data estimate that ~3-10% of patients with metastatic castration-resistant prostate cancer harbour liver metastases at the baseline, rising to 20-30% in post-treatment cohorts, suggesting that selective pressure imposed by novel therapies might promote metastatic spread to the liver. Liver metastases are associated with more aggressive tumour biology than lung metastases. Molecular profiling of liver lesions showed an enrichment of low androgen receptor, neuroendocrine phenotypes and high genomic instability. Despite advancements in molecular imaging modalities such as prostate-specific membrane antigen PET-CT, and liquid biopsy markers such as circulating tumour DNA, early detection of liver metastases from prostate cancer remains challenging, as both approaches are hampered by false positive and false negative results, impeding the accurate identification of early liver lesions. Current therapeutic strategies showed limited efficacy in this patient population. Emerging targeted radionuclide therapies, metastasis-directed therapy, and novel systemic agents have shown preliminary activity against liver metastases, but require further validation. Treatment with various novel prostate cancer therapies might lead to an increase in the prevalence of liver metastasis, underscoring the urgent need for coordinated efforts across preclinical and clinical researchers to improve characterization, monitoring, and management of liver metastases from prostate cancer. Elucidating molecular drivers of liver tropism and interactions with the liver microenvironment might ultimately help to identify actionable targets to enhance survival in this high-risk patient group.

Collapse

Affiliation(s)

Xudong Ni Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Yu Wei Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Xiaomeng Li Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Jian Pan Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Bangwei Fang Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Tingwei Zhang Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Ying Lu Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China
Dingwei Ye Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Shanghai Genitourinary Cancer Institute, Shanghai, China
Yao Zhu Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Shanghai Genitourinary Cancer Institute, Shanghai, China.

Collapse

Ahmed ME, Mahmoud AM, Reitano G, Zeina W, Lehner K, Day CA, Riaz I, Childs DS, Orme JJ, Tuba Kendi A, Johnson GB, Jeffrey Karnes R, Kwon ED, Andrews JR. Survival Patterns Based on First-site-specific Visceral Metastatic Prostate Cancer: Are Outcomes of Visceral Metastases the Same? EUR UROL SUPPL 2024;66:38-45. [PMID: 39040620 PMCID: PMC11260861 DOI: 10.1016/j.euros.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2024] [Indexed: 07/24/2024] Open

Abstract

Background and objective

Visceral metastatic disease in prostate cancer patients conveys a poor prognosis. Using advanced imaging techniques, studies have demonstrated increasing detection rates of visceral metastasis. Visceral metastases are now seen in up to 30-60% of prostate cancer patients. Survival patterns of site-specific visceral metastasis are described poorly in the literature. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis.

Methods

Retrospectively, we identified 203 prostate cancer patients with visceral metastases from the Mayo Clinic Advanced Prostate Cancer Registry. Patients were divided into three groups according to the first site of visceral metastases detected: lung, brain, or liver. Visceral metastases were detected primarily on either metabolic imaging (C-11 choline) or prostate-specific membrane antigen positron emission tomography computed tomography (CT) scan. Confirmation of visceral metastasis diagnosis was established with either biopsy when feasible or focused conventional imaging, including focused CT or magnetic resonance imaging. Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression model was conducted to assess different variables that affect overall and cancer-specific survival.

Key findings and limitations

Over a median (interquartile range) follow-up duration of 16.2 (3.9-49.8) mo, the overall and cancer-specific survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases than in patients with first-site brain or liver metastases (p < 0.0001). In univariate and multivariate analyses of factors impacting patients' overall and cancer-specific survival, a high prostate-specific antigen level at diagnosis of visceral metastasis, concomitant bone and lymph node disease, and more than four visceral metastases were associated with poor overall and cancer-specific survival (p < 0.05). On the contrary, first-site lung metastasis was associated with improved overall and cancer-specific survival, compared with first-site liver and brain metastases (p < 0.001).

Conclusions and clinical implications

These data suggest that prostate cancer patients with visceral metastatic disease have varying survival patterns according to first-site detected visceral metastasis. In our cohort, patients with first-site lung metastasis demonstrated better survival outcomes than patients with first-site brain or liver metastasis.

Patient summary

Our study explored the survival outcomes among patients with visceral metastatic prostate cancer employing cutting-edge imaging methods. Prostate cancer patients with metastases to different organs have different survival rates. Patients with cancer spreading to the lungs first showed better survival than those with cancer spreading to the brain or liver first.

Collapse

Mahmoud AM, Moustafa A, Day C, Ahmed ME, Zeina W, Marzouk UM, Basourakos S, Haloi R, Mahon M, Muniz M, Childs DS, Orme JJ, Riaz IB, Kendi AT, Stish BJ, Davis BJ, Kwon ED, Andrews JR. Prostate Cancer Lung Metastasis: Clinical Insights and Therapeutic Strategies. Cancers (Basel) 2024;16:2080. [PMID: 38893199 PMCID: PMC11171228 DOI: 10.3390/cancers16112080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/23/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024] Open

Mahmoud AM, Orme JJ, Childs DS, Ahmed ME, Rajkumar A, Kwon ED, Andrews JR. Prostate Cancer and Malignant Ascites: The Mayo Clinic Experience With a Rare and Aggressive Disease Progression. Clin Genitourin Cancer 2024;22:291-294. [PMID: 38101982 DOI: 10.1016/j.clgc.2023.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/18/2023] [Accepted: 11/19/2023] [Indexed: 12/17/2023]

Mahmoud AM, Childs DS, Ahmed ME, Tuba Kendi A, Johnson GB, Orme JJ, Stish BJ, Phillips RM, Park SS, Davis BJ, Andrews JR, Kwon ED. Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis. Prostate 2024;84:237-244. [PMID: 37899635 DOI: 10.1002/pros.24643] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/07/2023] [Accepted: 10/16/2023] [Indexed: 10/31/2023]

Abstract

BACKGROUND

Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes.

METHODS

We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups.

RESULTS

At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022).

CONCLUSIONS

In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Collapse

Shiner A, Sperandio RC, Naimi M, Emmenegger U. Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies. J Clin Med 2024;13:734. [PMID: 38337427 PMCID: PMC10856097 DOI: 10.3390/jcm13030734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/22/2024] [Accepted: 01/24/2024] [Indexed: 02/12/2024] Open

Sepe P, Procopio G, Pircher CC, Basso U, Caffo O, Cappelletti V, Claps M, De Giorgi U, Fratino L, Guadalupi V, Miodini P, De Marco C, Perrucci B, Mennitto A, Santini D, Spina F, Stellato M, de Braud F, Verzoni E. A phase II study evaluating the efficacy of enzalutamide and the role of liquid biopsy for evaluation of ARv7 in mCRPC patients with measurable metastases including visceral disease (Excalibur study). Ther Adv Med Oncol 2024;16:17588359231217958. [PMID: 38264520 PMCID: PMC10804904 DOI: 10.1177/17588359231217958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 11/15/2023] [Indexed: 01/25/2024] Open

Abstract

Background

Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis.

Objectives

Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes.

Methods

In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7.

Results

From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1-2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively.

Conclusion

The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites.

Trial registration

ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.

Collapse

Affiliation(s)

Pierangela Sepe Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Giacomo Venezian 1, Milan 20133, Italy
Giuseppe Procopio Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy Programma Prostata, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Chiara Carlotta Pircher Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Umberto Basso Oncology Unit 1, Department of Medical Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
Orazio Caffo Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy
Vera Cappelletti Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
Melanie Claps Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Ugo De Giorgi Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy
Lucia Fratino Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano, Italy
Valentina Guadalupi Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Patrizia Miodini Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
Cinzia De Marco Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
Bruno Perrucci Oncology Department, ASST Istituti Ospitalieri, Cremona, Italy
Alessia Mennitto Department of Medical Oncology, University Hospital Maggiore della Carità, Novara, Italy Medical Oncology, Department of Translational Medicine (DIMET), University of Eastern Piedmont (UPO), Novara, Italy
Daniele Santini Oncologia Medica, Campus Bio-Medico University of Rome, Rome, Italy University of Rome La Sapienza, Roma, Italy
Francesco Spina Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda, Milan, Italy
Marco Stellato Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Filippo de Braud Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Elena Verzoni Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

Collapse

Naderinezhad S, Zhang G, Wang Z, Zheng D, Hulsurkar M, Bakhoum M, Su N, Yang H, Shen T, Li W. A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression. Cancer Lett 2023;571:216333. [PMID: 37543278 PMCID: PMC11235056 DOI: 10.1016/j.canlet.2023.216333] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/24/2023] [Accepted: 08/02/2023] [Indexed: 08/07/2023]

Affiliation(s)

Samira Naderinezhad Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA
Guoliang Zhang Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Zheng Wang Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Dayong Zheng Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Mohit Hulsurkar Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA
Michael Bakhoum Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Ning Su Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Han Yang Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
Tao Shen Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
Wenliang Li Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.

Collapse

Soma T, Yoshida S, Wakejima R, Taguchi T, Fukuda S, Tanaka H, Yokoyama M, Ohashi K, Okubo K, Fujii Y. A case of repeat oligoprogressive castration-resistant prostate cancer treated with pulmonary metastasectomy. IJU Case Rep 2023;6:216-218. [PMID: 37405025 PMCID: PMC10315241 DOI: 10.1002/iju5.12589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 03/29/2023] [Indexed: 07/06/2023] Open

Yekedüz E, McKay RR, Gillessen S, Choueiri TK, Ürün Y. Visceral Metastasis Predicts Response to New Hormonal Agents in Metastatic Castration-Sensitive Prostate Cancer. Oncologist 2023:7135855. [PMID: 37084289 DOI: 10.1093/oncolo/oyad102] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 03/22/2023] [Indexed: 04/23/2023] Open

Keating S, Imtiaz A, Nahum K, Prasad A, Cheriyath P. An Interesting Case of Prostate Cancer Presenting With Colonic Metastasis. Cureus 2023;15:e34602. [PMID: 36883094 PMCID: PMC9985925 DOI: 10.7759/cureus.34602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2023] [Indexed: 02/05/2023] Open

Buxton AK, Abbasova S, Bevan CL, Leach DA. Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy. Cancers (Basel) 2022;14:6189. [PMID: 36551674 PMCID: PMC9777323 DOI: 10.3390/cancers14246189] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/12/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open

Galli L, Chiuri VE, Di Lorenzo G, Pisconti S, Rossetti S, Sirotova Z, Muto A, Petrioli R, De Tursi M, Sbrana A, Francolini G, Ardizzoia A, Scavelli C, Satta F, Quadrini S, Airoldi M, D'Aniello C, Bonetti A, Conforti S, Aieta M, Beccaglia P, Maestri A, Fratino L. First-line treatment of metastatic castration-resistant prostate cancer: the real-world Italian cohort of the Prostate Cancer Registry. TUMORI JOURNAL 2022;109:224-232. [PMID: 35400269 PMCID: PMC10070548 DOI: 10.1177/03008916221079662] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]

Abstract

BACKGROUND

With the availability of multiple treatment options for metastatic castration-resistant prostate cancer (mCRPC), new real-world data on disease management and drugs' performance are needed.

METHODS

We described characteristics, management and clinical outcomes of patients receiving first-line mCRPC treatment within the Italian cohort of the real-world, prospective, international Prostate Cancer Registry. Patients were enrolled consecutively (2013-2016) in 32 Italian sites and followed for 3 years.

RESULTS

238 patients were included: 157 received first-line abiraterone acetate plus prednisone ("abiraterone" thereafter) and 70 first-line docetaxel; 11 patients receiving other treatments were not considered. Compared with docetaxel-treated patients, those receiving abiraterone were significantly older (age ⩾75: 63.7% vs 38.6%), less frequently had a Gleason score >8 (48.2% vs 67.6%, p<0.005) at initial diagnosis, and more frequently an ECOG score ⩾1 (52.7% vs 36.2%, p<0.05) and comorbidities (76.4% vs 57.1%, p<0.05) at baseline; they reported a lower analgesic use (15.3% vs 30%, p<0.005). In the abiraterone group (median follow-up 22.1 months), median time to progression (TTP) and progression-free survival (PFS) were, respectively, 14.4 months (95% confidence interval, CI, 10.6-18.0) and 13.0 months (95% CI, 9.1-16.8); median overall survival (OS) was not reached, and 3-year OS was 59.1%. In the docetaxel treatment group (median follow-up 25.3 months), median TTP, PFS and OS were, respectively, 8.2 months (95% CI, 6.1-10.3), 8.2 months (95% CI, 5.8-10.3) and 33.2 months (95% CI, 19.2-not estimable).

CONCLUSION

This investigation provided valuable information on the overall mCRPC treatment pattern and the effectiveness of first-line abiraterone and docetaxel in a population representative of everyday practice.

Collapse

Affiliation(s)

Luca Galli Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
Vincenzo Emanuele Chiuri Medical Oncology Department, Ospedale Vito Fazzi, Lecce, Italy
Giuseppe Di Lorenzo Oncology Unit, Hospital "Andrea Tortora," ASL Salerno, Pagani, Italy
Salvatore Pisconti Unit of Medical Oncology, Ospedale S.G. Moscati, Taranto, Italy
Sabrina Rossetti Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy
Zuzana Sirotova Unit of Medical Oncology, Aosta Regional Hospital, Aosta, Italy
Andrea Muto Division of Medical Oncology, "San Giuseppe Moscati" Hospital, Avellino, Italy
Roberto Petrioli Oncology Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Michele De Tursi Department of Medical, Oral and Biotechnological Sciences and Center for Advanced Studies and Technology (CAST), G. D'Annunzio University, Chieti, Italy
Andrea Sbrana Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.,Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Giulio Francolini Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
Antonio Ardizzoia Oncology Department, Ospedale Alessandro Manzoni-ASST Lecco, Lecco, Italy
Claudio Scavelli Medical Oncology Unit, S. Cuore di Gesù Hospital, Gallipoli (LE), Italy
Francesco Satta Unit of Medical Oncology, Ospedale San Pietro, Fatebenefratelli, Rome, Italy
Silvia Quadrini Unit of Medical Oncology, Ospedale "SS Trinità" - ASL Frosinone, Sora, Italy
Mario Airoldi Oncology Unit 2, Città della Salute e della Scienza di Torino, Turin, Italy
Carmine D'Aniello Division of Medical Oncology, AORN Azienda dei Colli, Monaldi Hospital, Naples, Italy
Andrea Bonetti Department of Oncology, Mater Salutis Hospital - Az. ULSS 9 Scaligera, Legnago, Italy
Serafino Conforti Medical Oncology Unit, Annunziata Hospital, Cosenza, Italy
Michele Aieta Department of Onco-Hematology, Division of Medical Oncology, Centro di Riferimento Oncologico della Basilicata IRCCS, Rionero in Vulture, Italy
Patrizia Beccaglia Janssen SpA, Cologno Monzese, Italy
Antonio Maestri Medical Oncology Department, Santa Maria della Scaletta Hospital, Imola, Italy
Lucia Fratino Medical Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

Collapse

Baciarello G, Özgüroğlu M, Mundle S, Leitz G, Richarz U, Hu P, Feyerabend S, Matsubara N, Chi KN, Fizazi K. Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Eur J Cancer 2021;162:56-64. [PMID: 34953443 DOI: 10.1016/j.ejca.2021.11.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/03/2021] [Indexed: 11/03/2022]

Abstract

BACKGROUND

A post-hoc analysis of the phase-3 LATITUDE study assessed the impact of abiraterone acetate plus prednisone (AA+P) on overall survival (OS) and radiographic progression-free survival (rPFS) in men with metastatic castration-sensitive prostate cancer (mCSPC) and visceral metastases (VM).

METHODS

Newly diagnosed mCSPC patients were randomized (1:1) to AA+P and androgen deprivation therapy (ADT) or placebo+ADT. Patients with VM in liver or lungs with or without other soft tissue and bone metastases (based on CT/MRI) at baseline were analyzed, after 51.8 months' median follow-up. Co-primary endpoints, OS and rPFS, were analyzed.

RESULTS

Among 1199 patients enrolled, 228 (19%) had VM at baseline (114 each in AA+P and placebo groups), of which 53 (23.2%; AA+P = 29, Placebo = 24) had liver metastases and 117 (51.3%; AA+P = 60, Placebo = 57) had lung metastases. In patients with VM, treatment with AA+P versus placebo showed an improvement in OS (median 55.4 vs 33.0 months; HR = 0.582; 95%CI = 0.406-0.835;P = 0.0029) and rPFS (median 30.7 vs 18.3 months; HR = 0.527; 95%CI = 0.366-0.759;P = 0.0005), comparable to that of patients without VM. AA+P versus placebo in lung metastases patients was associated with greater improvement in OS (HR = 0.60; 95%CI = 0.35-1.04;P = 0.0678) than in liver metastases patients (HR = 0.82; 95%CI = 0.41-1.66;P = 0.5814). AA+P versus placebo showed improvement in rPFS in lung metastases patients (HR = 0.50; 95%CI = 0.29-0.89;P = 0.0157), but not in liver metastases patients (HR = 1.05; 95%CI = 0.53-2.09; P = 0.8970).

CONCLUSION

AA+P treatment improved both rPFS and OS in men with mCSPC and visceral disease, especially those with lung metastases. Men with liver metastases had a poorer prognosis and their optimal treatment remains to be defined.

REGISTRATION

ClinicalTrials.gov, number NCT01715285.

Collapse

Yeo AE, Hendrix A, Confente C, Christian N, Mansvelt B, Pairet G, Seront E. Highlighting the Place of Metastasis-Directed Therapy in Isolated Liver Metastases in Prostate Cancer: A Case Report. Front Oncol 2021;11:764758. [PMID: 34868986 PMCID: PMC8635688 DOI: 10.3389/fonc.2021.764758] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 10/27/2021] [Indexed: 11/13/2022] Open

Fallara G, Alverbratt C, Garmo H, Vikman H, Hjelm Eriksson M, Lissbrant IF, Stattin P. Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden. Acta Oncol 2021;60:1589-1596. [PMID: 34533422 DOI: 10.1080/0284186x.2021.1978539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]

Nakanishi S, Goya M, Tamaki M, Oshiro T, Saito S. Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer. BMC Res Notes 2021;14:227. [PMID: 34082809 PMCID: PMC8176613 DOI: 10.1186/s13104-021-05641-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 05/27/2021] [Indexed: 12/02/2022] Open

Oruç Z, Kaplan MA, Karaağaç M, Özyurt N, Tatlı AM, Kaya AO, Menekşe S, Kut E, Koca S, Sever ÖN, Yasin İ, Ebinç S, Zeynelgil E, Sakin A, Turhal NS, Isikdogan A. Efficacy and tolerability of current treatments for hormone-refractory prostate cancer patients with visceral metastases. Future Oncol 2021;17:1611-1624. [PMID: 33631986 DOI: 10.2217/fon-2020-1032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open

Schutz FAB, Sirachainan E, Kuppusamy S, Hoa NTT, Dejthevaporn T, Bahadzor B, Toan VQ, Chansriwong P, Alip A, Hue NTM, Parinyanitikul N, Tan AL, Hoang VDK, Tienchaiananda P, Chinchapattanam SND, Garg A. Optimizing outcomes for patients with metastatic prostate cancer: insights from South East Asia Expert Panel. Ther Adv Med Oncol 2021;13:1758835920985464. [PMID: 33747148 PMCID: PMC7905487 DOI: 10.1177/1758835920985464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 12/14/2020] [Indexed: 11/17/2022] Open

Gschwend JE, Miller K. Abiraterone acetate plus prednisone/prednisolone in hormone-sensitive and castration-resistant metastatic prostate cancer. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2020. [DOI: 10.1080/23808993.2021.1863781] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]

Procopio G, Chiuri VE, Giordano M, Mantini G, Maisano R, Bordonaro R, Calvani N, Facchini G, De Placido S, Airoldi M, Sbrana A, Gasparro D, Ludovico GM, Guglielmini P, Naglieri E, Fagnani D, Aglietta M, Schips L, Beccaglia P, Sciarra A, Livi L, Santini D. Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study. Ther Adv Med Oncol 2020;12:1758835920968725. [PMID: 33193831 PMCID: PMC7604981 DOI: 10.1177/1758835920968725] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 10/02/2020] [Indexed: 12/24/2022] Open

Affiliation(s)

Giuseppe Procopio Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, Milan, 20133, Italy
Vincenzo Emanuele Chiuri Medical Oncology Department, Ospedale Vito Fazzi, Lecce, Puglia, Italy
Monica Giordano Medical Oncology Division, ASST-Lariana, Como, Lombardia, Italy
Giovanna Mantini Radiochemotherapy Unit, Department of Diagnostics for Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico A. Gemelli IRCCS, Rome - University Department of Radiological and Hematological Sciences, Università Cattolica Sacro Cuore, Italy
Roberto Maisano Department of Oncology, A.O. Bianchi-Melacrino-Morelli, Reggio Calabria, Calabria, Italy
Roberto Bordonaro MD - ARNAS Garibaldi, Catania, Sicilia, Italy
Nicola Calvani Medical Oncology Unit, Antonio Perrino Hospital, Brindisi, Puglia, Italy
Gaetano Facchini Departmental Unit of Experimental Uro-Andrological Clinical Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Naples, Italy
Sabino De Placido Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Campania, Italy
Mario Airoldi Oncology Unit 2 - Città della Salute e della Scienza di Torino, Turin, Piemonte, Italy
Andrea Sbrana Medical Oncology Unit 2, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Donatello Gasparro Medical Oncology Unit, Department of General and Specialistic Medicine, University Hospital of Parma, Parma, Italy
Giuseppe Mario Ludovico Department of Urology, Ospedale F. Miulli, Acquaviva delle Fonti, Bari, Italy
Pamela Guglielmini Oncology Unit, SS Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy
Emanuele Naglieri Medical Oncology Unit, IRCCS Giovanni Paolo II, Bari, Italy
Daniele Fagnani Medical Oncology Division, ASST Vimercate, Vimercate, Italy
Massimo Aglietta Department of Oncology, University of Turin; Candiolo Cancer Institute - FPO- IRCCS, Candiolo, Italy
Luigi Schips Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti, Urology unit, "SS. Annunziata Hospital", Chieti, Italy
Patrizia Beccaglia Janssen SpA, Cologno Monzese, Italy
Alessandro Sciarra Department of Urology, Sapienza Rome University Policlinico Umberto I, Rome, Italy
Lorenzo Livi Department of Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
Daniele Santini Department of Medical Oncology, University Campus Biomedico, Rome, Italy

Collapse

Nafissi NN, Kosiorek HE, Butterfield RJ, Moore C, Ho T, Singh P, Bryce AH. Evolving Natural History of Metastatic Prostate Cancer. Cureus 2020;12:e11484. [PMID: 33329980 PMCID: PMC7735525 DOI: 10.7759/cureus.11484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open

Abiraterone acetate and acute leukemia: a casual association? Anticancer Drugs 2020;32:102-104. [PMID: 32932280 DOI: 10.1097/cad.0000000000000988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Lobo-Martins S, Ferreira AR, Mansinho A, Casimiro S, Leitzel K, Ali S, Lipton A, Costa L. Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases. Cancers (Basel) 2020;12:cancers12082034. [PMID: 32722128 PMCID: PMC7463577 DOI: 10.3390/cancers12082034] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 07/16/2020] [Accepted: 07/21/2020] [Indexed: 11/23/2022] Open

Manceau C, Mourey L, Pouessel D, Ploussard G. Abiraterone acetate in combination with prednisone in the treatment of prostate cancer: safety and efficacy. Expert Rev Anticancer Ther 2020;20:629-638. [PMID: 32552120 DOI: 10.1080/14737140.2020.1785289] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Khreish F, Kochems N, Rosar F, Sabet A, Ries M, Maus S, Saar M, Bartholomä M, Ezziddin S. Response and outcome of liver metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing ¹⁷⁷Lu-PSMA-617 radioligand therapy. Eur J Nucl Med Mol Imaging 2020;48:103-112. [PMID: 32378019 DOI: 10.1007/s00259-020-04828-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/13/2020] [Indexed: 12/24/2022]

Abstract

PURPOSE

Little is known about the efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) against liver metastases of metastatic castration-resistant prostate cancer (mCRPC). We retrospectively analyzed efficacy-related outcomes of ¹⁷⁷Lu-PSMA-617 RLT in this setting and potential predictors of those outcomes.

METHODS

Twenty-eight consecutive mCRPC patients with liver metastases given ¹⁷⁷Lu-PSMA-617 RLT were analyzed retrospectively. Their planned regimen was 4-6 cycles at 6 ± 2-week intervals; the mean activity/cycle was 6.5 ± 0.5 GBq. Hepatic response was determined by modified positron emission tomography response criteria in solid tumors; association of such response with overall survival (OS) was tested, as were relationships of the selected patient, disease, and treatment characteristics with hepatic progression-free survival (PFS_hep) and OS. Survival analyses used Kaplan-Meier curves, log-rank test at p < 0.05 significance, and Cox proportional-hazards modeling.

RESULTS

Median (minimum-maximum) follow-up was 37.5 (2.3-50.6) months. In liver metastases, complete or partial response was observed in 6 patients (21%) each, and stable disease in 1 (4%), for hepatic disease control in 46%. Overall, median (95% confidence interval) PFS_hep was 5.7 (2.2-9.2) months, and OS, 11.7 (3.0-20.4) months. Patients with hepatic disease control did not reach the median OS, while those with hepatic progressive disease had median OS (95% confidence interval) of 6.4 (1.6-11.1) months. In multivariate analysis, hepatic disease control by ¹⁷⁷Lu-PSMA-617 RLT was significantly independently associated with OS, as was a prostate-specific antigen decline of ≥ 50% after 2 RLT cycles, and good baseline performance status (Eastern Cooperative Oncology Group 0-1). Hepatic tumor burden (≤ 25% vs. > 25% of liver volume) had no apparent relationship with hepatic tumor response, PFS_hep, or OS.

CONCLUSION

¹⁷⁷Lu-PSMA-617 RLT frequently controlled liver metastases, resulting in long PFS_hep and significantly improved OS. Hepatic tumor burden appeared to lack any relationship with treatment efficacy, supporting ¹⁷⁷Lu-PSMA-617 RLT of late-stage/end-stage mCRPC with liver metastases.

Collapse

Valero J, Peleteiro P, Henríquez I, Conde A, Piquer T, Lozano A, Soler CC, Muñoz J, Illescas A, Jove J, Flores MM, Baquedano J, Diezhandino P, de Celis RP, Pardo EH, Samper P, Villoslada I, Eguiguren M, Millan V. Age, Gleason Score, and PSA are important prognostic factors for survival in metastatic castration-resistant prostate cancer. Results of The Uroncor Group (Uro-Oncological Tumors) of the Spanish Society of Radiation Oncology (SEOR). Clin Transl Oncol 2020;22:1378-1389. [PMID: 31989474 DOI: 10.1007/s12094-019-02274-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Accepted: 12/16/2019] [Indexed: 12/14/2022]

Abstract

INTRODUCTION

The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient's individual clinical, radiological, and biological characteristics.

OBJECTIVE

To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain.

MATERIALS AND METHODS

Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan-Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS.

RESULTS

A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68 years (range 45-89). At a median follow-up of 35 months, OS at 1, 3, and 5 years were 92%, 38%, and 28%, respectively. Grades 1-2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009).

CONCLUSIONS

Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.

Collapse

Wang Z, Zhao Y, An Z, Li W. Molecular Links Between Angiogenesis and Neuroendocrine Phenotypes in Prostate Cancer Progression. Front Oncol 2020;9:1491. [PMID: 32039001 PMCID: PMC6985539 DOI: 10.3389/fonc.2019.01491] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 12/11/2019] [Indexed: 12/11/2022] Open

Cui PF, Cong XF, Gao F, Yin JX, Niu ZR, Zhao SC, Liu ZL. Prognostic factors for overall survival in prostate cancer patients with different site-specific visceral metastases: A study of 1358 patients. World J Clin Cases 2020;8:54-67. [PMID: 31970170 PMCID: PMC6962083 DOI: 10.12998/wjcc.v8.i1.54] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 12/09/2019] [Accepted: 12/14/2019] [Indexed: 02/06/2023] Open

Abstract

BACKGROUND

Distant metastasis, particularly visceral metastasis (VM), represents an important negative prognostic factor for prostate cancer (PCa) patients. However, due to the lower rate of occurrence of VM, studies on these patients are relatively rare. Consequently, studies focusing on prognostic factors associated with PCa patients with VM are highly desirable.

AIM

To investigate the prognostic factors for overall survival (OS) in PCa patients with lung, brain, and liver metastases, respectively, and evaluate the impact of site-specific and number-specific VM on OS.

METHODS

Data on PCa patients with VM were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Univariate and multivariate Cox regression analyses were used to analyze the association between clinicopathological characteristics and survival of patients with different site-specific VM. Kaplan-Meier analyses and Log-rank tests were performed to analyze the differences among the groups.

RESULTS

A total of 1358 PCa patients with site-specific VM were identified from 2010 to 2015. Older age (> 70 years) (P < 0.001), higher stage (T3/T4) (P = 0.004), and higher Gleason score (> 8) (P < 0.001) were found to be significant independent prognostic factors associated with poor OS in PCa patients with lung metastases. Higher stage (T3/T4) (P = 0.047) was noted to be the only independent risk factor affecting OS in PCa patients with brain metastases. Older age (> 70 years) (P = 0.010) and higher Gleason score (> 8) (P = 0.001) were associated with shorter OS in PCa patients with liver metastases. PCa patients with isolated lung metastases exhibited significantly better survival outcomes compared with PCa patients with other single sites of VM (P < 0.001). PCa patients with a single site of VM exhibited a superior OS compared with PCa patients with multiple sites of VM (P < 0.001).

CONCLUSION

This is the first Surveillance, Epidemiology, and End Results-based study to determine prognostic factors affecting OS in PCa patients with different site-specific VM. Clinical assessments of these crucial prognostic factors become necessary before establishing a treatment strategy for these patients with metastatic PCa.

Collapse

Yoshida S, Takahara T, Ishii C, Arita Y, Waseda Y, Kijima T, Yokoyama M, Ishioka J, Matsuoka Y, Saito K, Fujii Y. METastasis Reporting and Data System for Prostate Cancer as a Prognostic Imaging Marker in Castration-resistant Prostate Cancer. Clin Genitourin Cancer 2019;18:e391-e396. [PMID: 31902713 DOI: 10.1016/j.clgc.2019.12.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 11/28/2019] [Accepted: 12/09/2019] [Indexed: 01/30/2023]

Chen HY, Aggarwal R, Bok RA, Ohliger MA, Zhu Z, Lee P, Gordon JW, van Criekinge M, Carvajal L, Slater JB, Larson PEZ, Small EJ, Kurhanewicz J, Vigneron DB. Hyperpolarized ¹³C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study. Prostate Cancer Prostatic Dis 2019;23:269-276. [PMID: 31685983 PMCID: PMC7196510 DOI: 10.1038/s41391-019-0180-z] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 10/10/2019] [Accepted: 10/18/2019] [Indexed: 11/27/2022]

Abstract

Background

Hyperpolarized (HP) ¹³C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP ¹³C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera.

Methods

Six patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized ¹³C-pyruvate, where pyruvate-to-lactate conversion rate (k_PL) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses.

Results

We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean k_PL value of 0.020 ± 0.006 (s⁻¹) and 0.026 ± 0.000 (s⁻¹) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high k_PL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of k_PL from 0.026 at baseline to 0.015 (s⁻¹) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9).

Conclusions

HP ¹³C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k_PL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP ¹³C-pyruvate MRI in the setting of advanced prostate cancer.

Collapse

Teply BA, Qiu F, Antonarakis ES, Carducci MA, Denmeade SR. Risk of development of visceral metastases subsequent to abiraterone vs placebo: An analysis of mode of radiographic progression in COU-AA-302. Prostate 2019;79:929-933. [PMID: 31059588 DOI: 10.1002/pros.23798] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 02/14/2019] [Accepted: 03/05/2019] [Indexed: 11/10/2022]

Ranasinghe L, Cotogno P, Ledet E, Bordlee B, Degeyter K, Nguyen N, Steinberger A, Manogue C, Barata P, Lewis BE, Sartor AO. Relationship between serum markers and volume of liver metastases in castration-resistant prostate cancer. Cancer Treat Res Commun 2019;20:100151. [PMID: 31128516 DOI: 10.1016/j.ctarc.2019.100151] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 05/09/2019] [Accepted: 05/13/2019] [Indexed: 06/09/2023]

Abstract

BACKGROUND

Prostate cancer patients with liver metastases have a poor prognosis. To date, no study exists investigating the relationship between liver tumor burden and clinical laboratory markers.

MATERIALS AND METHODS

Metastatic castrate-resistant prostate cancer (mCRPC) patients with radiographic evidence of liver metastases were selected for this study. Volumetric measurements of liver metastases were ascertained for all available patients. Prostate specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), total bilirubin and hemoglobin (HGB) levels were then assessed to coincide with the scan dates. Univariate and multivariate mixed-model regression analysis were performed to evaluate the relationship between laboratory markers and liver lesion volume. Data sets with non-normal distribution were logarithmically transformed. Akaike information criteria (AIC) was used to identify the most reliable multivariate model.

RESULTS

In our heavily pretreated liver-metastatic patient population, univariate analysis demonstrated a statistically significant positive correlation between PSA (p = 0.0002), ALP (p = 0.0305), AST (p < 0.0001), ALT (p = 0.0049), and LDH (p = 0.0019) and liver lesion volume. Additionally, ALB (p = 0.0006) and HGB (p = 0.0103) had statistically significant negative correlation. Multivariate analysis identified AST and hemoglobin assessments as the best predictors of increasing liver lesion burden. Preliminary data on circulating tumor DNA (ctDNA) mutational and amplification findings are also reported.

CONCLUSIONS

Analysis identified AST and hemoglobin as optimal predictors of liver lesion volume. These patients have a heavy burden of ctDNA abnormalities. Further studies with a larger patient population are needed to verify these results. Micro Abstract: This study investigates the association between liver lesion burden and clinical laboratory markers in castrate-resistant prostate cancer patients with hepatic metastases. Our univariate analysis identified multiple laboratory markers as significant indicators of worsening hepatic disease. Multivariate analysis demonstrated that AST and hemoglobin were the most effective predictors of change in liver lesion volume.

Collapse

Scott LJ. Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Drugs 2019;77:1565-1576. [PMID: 28819727 DOI: 10.1007/s40265-017-0799-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Therapeutic options for first-line metastatic castration-resistant prostate cancer: Suggestions for clinical practise in the CHAARTED and LATITUDE era. Cancer Treat Rev 2019;74:35-42. [DOI: 10.1016/j.ctrv.2019.01.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 01/03/2019] [Accepted: 01/04/2019] [Indexed: 12/11/2022]

Abiraterone acetate treatment in patients with castration-resistant prostate cancer with visceral metastases. Anticancer Drugs 2019;30:179-185. [DOI: 10.1097/cad.0000000000000703] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]

Gómez-Veiga F, Álvarez-Ossorio JL, Carballido-Rodríguez J, Juárez-Soto A, Rodríguez-Antolín A, Cozar-Olmo JM. Radium-223 for the treatment of metastatic castration-resistant prostate cancer: A window of opportunity. Actas Urol Esp 2018;42:616-624. [PMID: 30041891 DOI: 10.1016/j.acuro.2018.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 05/07/2018] [Indexed: 11/30/2022]

Katsui M, Ohigashi T, Kosaka T, Bessho H, Arakawa T. Remarkable response to abiraterone acetate in castration-resistant prostate cancer patient with aggressive liver metastasis. IJU Case Rep 2018;2:12-14. [PMID: 32743362 PMCID: PMC7292117 DOI: 10.1002/iju5.12026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 10/15/2018] [Indexed: 11/08/2022] Open

Ingrosso G, Detti B, Scartoni D, Lancia A, Giacomelli I, Baki M, Carta G, Livi L, Santoni R. Current therapeutic options in metastatic castration-resistant prostate cancer. Semin Oncol 2018;45:303-315. [PMID: 30446166 DOI: 10.1053/j.seminoncol.2018.10.001] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 07/30/2018] [Accepted: 10/15/2018] [Indexed: 11/11/2022]

Abstract

BACKGROUND

The tumors of many patients with prostate cancer eventually become refractory to androgen deprivation therapy with progression to metastatic castration-resistant disease. Significant advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been made in recent years, and new treatment strategies have recently been made available. The aim of this report was to schematically review all the approved pharmacologic treatment options for patients with mCRPC through 2018, analyzing the efficacy and possible side effects of each therapy to assist clinicians in reaching an appropriate treatment decision. New biomarkers potentially of aid in the choice of treatment in this setting are also briefly reviewed.

METHODS

We performed a literature search of clinical trials of new drugs and treatments for patients diagnosed with mCRPC published through 2018.

RESULTS

Two new hormonal drugs, abiraterone acetate and enzalutamide have been approved by FDA in 2011 and 2012, respectively for the treatment of patients with mCRPC and have undergone extensive testing. While these treatments have shown a benefit in progression-free and overall survival, the appropriate sequencing must still be determined so that treatment decisions can be made based on their specific clinical profile. Cabazitaxel has been shown to be an efficient therapeutic option in a postdocetaxel setting, while its role in chemotherapy-naïve patients must still be determined. Sipuleucel-T and radium-223 have been studied in patients without visceral metastases and have achieved overall survival benefits with good safety profiles. The feasibility and efficacy of combinations of new treatments with other known therapies such as chemotherapy are currently under investigation.

CONCLUSIONS

Drug development efforts continue to attempt to prolong survival and improve quality of life in the mCRPC setting, with several therapeutic options available. Ongoing and future trials are needed to further assess the efficacy and safety of these new drugs and their interactions, along with the most appropriate sequencing.

Collapse

Al-Ali BM, Eredics K, Madersbacher S, Schauer I. Abiraterone acetate, enzalutamide and their sequence for castration-resistant prostate cancer. Wien Klin Wochenschr 2018;130:659-664. [DOI: 10.1007/s00508-018-1394-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 09/21/2018] [Indexed: 10/28/2022]

Yokom DW, Stewart J, Alimohamed NS, Winquist E, Berry S, Hubay S, Lattouf JB, Leonard H, Girolametto C, Saad F, Sridhar SS. Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel. Can Urol Assoc J 2018;12:E365-E372. [PMID: 29629866 DOI: 10.5489/cuaj.5108] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Su J, Aslim EJ, Aydin H, Tan PH, Ho HSS. A rare case of isolated castrate resistant bilateral testicular metastases in advanced prostate cancer. Asian J Urol 2018;5:127-130. [PMID: 29736376 PMCID: PMC5934351 DOI: 10.1016/j.ajur.2017.03.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 06/23/2016] [Accepted: 12/02/2016] [Indexed: 11/24/2022] Open

Verzoni E, De Giorgi U, Derosa L, Caffo O, Boccardo F, Facchini G, Porcu L, De Vincenzo F, Zaniboni A, Chiuri VE, Fratino L, Santini D, Adamo V, De Vivo R, Dinota A, Messina C, Ricotta R, Caserta C, Scavelli C, Susi M, Tartarone A, Surace G, Mosca A, Bruno M, Barni S, Grassi P, Procopio G. Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study. Oncotarget 2018;7:40085-40094. [PMID: 27223078 PMCID: PMC5129994 DOI: 10.18632/oncotarget.9485] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Accepted: 04/10/2016] [Indexed: 12/19/2022] Open

Affiliation(s)

Elena Verzoni Unit of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Ugo De Giorgi Department of Medical Oncology, IRST, IRCCS, Meldola, Italy
Lisa Derosa Unit of Medical Oncology 2, Istituto Toscano Tumori, Pisa, Italy
Orazio Caffo Ospedale Santa Chiara, Trento, Italy
Francesco Boccardo IRCCS AOU San Martino IST and University of Genoa, Genova, Italy
Gaetano Facchini Unit of Medical Oncology, Department of Uro-Gynecological Oncology, Istituto Nazionale Tumori, Fondazione G. Pascale IRCCS, Naples, Italy
Luca Porcu Department of Oncology, IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
Fabio De Vincenzo Istituto Clinico Humanitas, Rozzano, Italy
Alberto Zaniboni Fondazione Poliambulanza, Brescia, Italy
Vincenzo Emanuele Chiuri Ospedale Vito Fazzi, Lecce, Italy
Lucia Fratino Istituto Nazionale Tumori CRO, Aviano, Italy
Daniele Santini Policlinico Universitario Campus Biomedico, Roma, Italy
Vincenzo Adamo Medical Oncology Unit, AO Papardo, Messina, Italy
Rocco De Vivo Ospedale San Bortolo, Vicenza, Italy
Angelo Dinota Ospedale San Carlo, Potenza, Italy
Caterina Messina Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
Riccardo Ricotta Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy
Claudia Caserta AO Santa Maria, Terni, Italy
Claudio Scavelli Ospedale S. Cuore di Gesù, Gallipoli, Italy
Marina Susi Ospedale Madonna delle Grazie, Matera, Italy
Alfredo Tartarone IRCCS Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, Italy
Giuseppe Surace Ospedale D. Camberlingo, Francavilla Fontana, Italy
Alessandra Mosca AOU Maggiore della Carità, Novara, Italy
Michele Bruno PO San G. Moscati, ASL Taranto, Italy
Sandro Barni AO, Treviglio, Italy
Paolo Grassi Unit of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Giuseppe Procopio Unit of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

Collapse

Foroughi Moghadam MJ, Taheri S, Peiravian F. A Systematic Review of Clinical Practice Guidelines for Castration-Resistant Prostate Cancer. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2018;17:17-37. [PMID: 29796026 PMCID: PMC5958321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]

Abstract

Cancer constitutes a huge burden on societies in countries with any level of economic development. Prostate cancer is the first most diagnosed cancer of men in developed countries and the forth one in developing countries in terms of incidence rate. It is also the third incident cancer of men in Iran along with a prevalence of about 10,000 cases. Castration-resistant prostate cancer (CRPC) is a severe stage of the disease with a number of newly discovered treatment options. These therapeutic alternatives including abiraterone acetate, enzalutamide, cabazitaxel, immunotherapy with sipuleucel-T, radiopharmaceuticals and bone-targeted therapies (zoledronic acid, denosumab) along with docetaxel have made the decision making process complex and challenging for clinicians. In addition to the challenges of selecting the best-fit treatment, high costs of new pharmaceuticals and technologies necessitates the health policy-makers to develop practice guidelines in adaptation with local resources and limitations. The aim of this paper is to review the clinical guidelines for the management of CRPC. For better comprehension of guideline recommendations, the main clinical trials on new treatments were also identified. The efficacy and safety outcomes including but not limited to overall survival, progression free survival, quality of life and adverse effects were summarized. The guidelines of American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EUA), Spanish Oncology Genitourinary Group (SOGG), Asian Oncology Summit, Saudi Oncology Society-Saudi Urology Association combined guideline, National Institute for Health and Care Excellence (NICE) and Canadian Urological Association-Canadian Urologic Oncology Group (CUA-CUOG) were covered in this paper.

Collapse

Poorthuis MHF, Vernooij RWM, van Moorselaar RJA, de Reijke TM. Second-line therapy in patients with metastatic castration-resistant prostate cancer with progression after or under docetaxel: A systematic review of nine randomized controlled trials. Semin Oncol 2017;44:358-371. [PMID: 29580437 DOI: 10.1053/j.seminoncol.2017.10.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 04/24/2017] [Accepted: 10/03/2017] [Indexed: 11/11/2022]

Alumkal JJ, Chowdhury S, Loriot Y, Sternberg CN, de Bono JS, Tombal B, Carles J, Flaig TW, Dorff TB, Phung D, Forer D, Noonberg SB, Mansbach H, Beer TM, Higano CS. Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial. Clin Genitourin Cancer 2017;15:610-617.e3. [DOI: 10.1016/j.clgc.2017.02.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Revised: 02/06/2017] [Accepted: 02/19/2017] [Indexed: 10/20/2022]

Pascale M, Azinwi CN, Marongiu B, Pesce G, Stoffel F, Roggero E. The outcome of prostate cancer patients treated with curative intent strongly depends on survival after metastatic progression. BMC Cancer 2017;17:651. [PMID: 28923109 PMCID: PMC5604496 DOI: 10.1186/s12885-017-3617-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 08/28/2017] [Indexed: 01/25/2023] Open

Abstract

BACKGROUND

Five-year survival in patients with localized prostate cancer (PCa) is nearly 100%, but metastatic disease still remains incurable. Clinical management of metastatic patients has become increasingly complex as novel therapeutic strategies have emerged. This study aims at evaluating the impact of the first metastatic progression on the outcome of PCa patients treated with curative intent.

METHODS

The analysis was conducted using data of 913 cases of localized PCa diagnosed between 2000 and 2014. All patients were treated with curative surgery (N = 382) or radiotherapy (N = 531) with or without adjuvant therapy. All metastases were radiologically documented. The prognostic impact of the first site of metastasis on metastasis-free survival (MFS) and PCa-specific survival (PCaSS) was investigated by univariate and multivariate analyses.

RESULTS

One hundred and thirty-six (14.9%) patients developed a metastatic hormone-sensitive PCa and had a median PCaSS of 50.4 months after first metastatic progression. Bone (N = 50, 36.8%) and LN or locoregional (N = 52, 38.2%) metastases occurred more frequently with a median PCaSS of 39.7 and 137 months respectively (p < 0.0001). Seven patients developed visceral metastasis only (5.1%; liver, lung, brain) and 27 (19.9%) concurrent metastases; this last group was associated with the worst survival with a median value of only 17 months. Thus, each subgroup exhibited a survival after metastasis significantly different from each other. In multivariate analysis the site of the first metastasis was an independent prognostic factor for PCaSS along with Gleason score at diagnosis. The correlation between survival and first site of metastasis was confirmed separately for each therapy subgroup. Median metastasis-free survival from primary diagnosis to first metastasis was not correlated with the first site of metastasis.

CONCLUSIONS

In non-metastatic PCa patients treated with curative intent, the PCa-specific survival time depends on the time after metastatic progression rather than the time from diagnosis to metastasis. Moreover, the site of first metastasis is an independent prognostic factor for PCaSS. Our data confirm that the first metastatic event may confer a differential prognostic impact and may help in identifying patient at high risk of death supporting the treatment-decision making process following metastatic progression.

Collapse