Turning the tide: From cervical cancer's grip to complete response: A case report

Abstract

BACKGROUND

Cervical cancer is a formidable global health issue, particularly affecting women in lower-middle-income countries with little or no access to preventative vaccines, screening programs, and treatment modalities. The case report presents a unique case of a large cervical cancer achieving complete response (CR) with concurrent chemoradiotherapy (CCRT), highlighting the effectiveness of this treatment approach even in advanced stages and underscoring the importance of adaptive radiotherapy (RT) in optimizing patient outcomes.

CASE SUMMARY

We present the case of a 53-year-old woman who presented with four years of abnormal vaginal bleeding and was found to have p16-positive, moderately differentiated cervical squamous cell carcinoma. The tumor measured 14 cm × 12 cm × 8 cm, the largest size reported in the literature to achieve CR with CCRT. Despite this monumental feat, the patient remained disease-free and is currently on follow-up for 2 years; however, she continued to suffer from substantial morbidity caused by a vesicovaginal fistula and hydronephrosis, underscoring the continuing impact of cervical cancer on quality of life.

CONCLUSION

In this case report, we highlight the effectiveness of CCRT in achieving CR, even in cases of bulky cervical cancer, with adaptive RT offering a customized strategy to improve patient outcomes. We also emphasize the necessity for multidisciplinary team discussions and highlight the need for strategies to mitigate treatment-related toxicities and long-term complications.

Key Words: Cervical cancer; Chemoradiotherapy; Adaptive radiotherapy; Case report

Core Tip: In this report, we highlight the effectiveness of chemoradiation in achieving complete response, even in cases of bulky cervical cancer with the largest primary tumor reported in the literature, using adaptive radiotherapy offering a customized strategy to improve patient outcomes.

INTRODUCTION

According to data from the Global Cancer Observatory, cervical cancer ranks eighth among all cancers in incidence and ninth among all cancers in mortality[1]. In Jordan, 115 new cases and 71 cervical cancer deaths are reported annually. Being a low middle income country (LMIC), Jordan is subject to a number of barriers, such as a lack of screening services and limited awareness of and access to healthcare, which are associated with a higher incidence of presentation at advanced stages[2,3]. Locally advanced cervical cancer is typically treated with concurrent chemoradiotherapy (CCRT), which has been shown to improve overall survival (OS) and disease-free survival compared with radiotherapy (RT) alone[4-6]. Prognostic factors impacting outcomes in this patient population included patient age, stage, lymph node status[7,8], tumor size, and tumor volume reduction rate (TVRR)[9].

We present the case of a 53-year-old woman who was diagnosed with remarkably large cervical cancer and achieved complete response (CR) with CCRT. To the best of our knowledge, this is the largest case of primary cervical carcinoma that has achieved a CR following definitive CCRT.

CASE PRESENTATION

Chief complaints

Intermittent abnormal vaginal bleeding for four years’ duration.

History of present illness

A 53-year-old woman, gravida 5, para 5, with a 25-pack/year cigarette-smoking history presented with a complaint of abnormal vaginal bleeding for the past four years. This was associated with intense lower abdominal pain and watery vaginal discharge, which had increased over the last few months.

History of past illness

She had no significant medical or surgical history.

Personal and family history

She had no family history of malignancy.

Physical examination

Speculum examination at presentation showed a large, ugly mass measuring approximately 8 cm × 9 cm, replacing the cervix with watery discharge and a foul smell. A subsequent biopsy revealed p16-positive moderately differentiated squamous cell carcinoma (SCC).

Laboratory examinations

Her initial labs showed unremarkable liver function test results and electrolyte levels: Creatinine, 1 mg/dL; urea, 37 mg/dL; and hemoglobin level of 13.9 g/dL. Urine analysis and culture revealed a urinary tract infection (UTI) for which she was treated with antibiotics.

Imaging examinations

Computed tomography (CT) scan of the chest, abdomen and pelvis, and positron emission tomography (PET) illustrated a large pelvic mass centered at the uterine cervix and infiltrating most of the uterine body with extension to the lower vagina and involvement of the urethra, with maximum standardized uptake value (SUV_max) of 19 with multiple bilateral pelvic lymph nodes, the largest being a right external iliac lymph node measuring about 1.2 cm × 1.5 cm with SUV_max of 4.4 with no evidence of extra pelvic disease. Magnetic resonance imaging (MRI) revealed a bulky pelvic mass of cervical origin measuring 14 cm × 12 cm × 8 cm, as well as extensive parametrial invasion and invasion of the posterior and superior bladder walls, including both ureterovesical junctions and lower ureters, causing moderate bilateral hydronephrosis and hydroureter. The tumor abutted the rectosigmoid without definite invasion, as shown in Figure 1. Her final International Federation of Gynecology and Obstetrics (FIGO) stage was IVA.

Figure 1 Pelvic magnetic resonance imaging scan at diagnosis, showing bulky cervical tumor measured in axial, sagittal and coronal views. A: Axial view; B: Sagittal view; C: Coronal view.

MULTIDISCIPLINARY EXPERT CONSULTATION

The patient's case was discussed at the Gynecology-Oncology Multidisciplinary Clinic, and we decided to proceed with CCRT.

FINAL DIAGNOSIS

Locally advanced cervical SCC.

TREATMENT

She started on cisplatin-based CCRT. However, owing to the development of acute kidney injury (AKI), she was switched to carboplatin-based therapy after the first cycle of cisplatin. Thus, she was subsequently scheduled for and received CCRT, as 75 mg of cisplatin for 1 cycle and 169 mg of weekly carboplatin for 3 cycles, concurrent with external beam RT (EBRT) over two phases, first of 45 Gy in 25 fractions, followed by re-evaluation for intra-cavitary brachytherapy (ICBT). However, upon examination under anesthesia, the proximal vaginal vault was found to be large, making probe fixation difficult, along with a large vesicovaginal fistula that precluded bladder filing and complicated packing. Accordingly, the patient was deemed unfit for brachytherapy boost and was planned for and received EBRT boost to the pelvis of 20 Gy in 10 fractions via volumetric arc therapy.

During treatment, the patient's clinical course was not smooth, as it was complicated by the aforementioned hydroureteronephrosis and AKI, the former of which necessitated bilateral nephrostomy placement, as well as a complicated UTI with extended spectrum beta-lactamase-positive Escherichia coli, hypercalcemia, anemia, and thrombocytopenia, which caused her to skip her last two cycles of chemotherapy. However, she was responsive to treatment, requiring repeated CT simulation and re-planning after 16 fractions of therapy because of a significant decrease in the size of the tumor seen on cone-beam CT. Furthermore, pelvic MRI ordered after 20 fractions of CCRT revealed regression of the uterine cervix tumor by at least 40%, with a dramatic decrease in the invasion of the urinary bladder and vagina and partial regression of the aforementioned parametrial invasion.

OUTCOME AND FOLLOW-UP

On follow-up, the patient continued to show a sustained response to therapy. Pelvic MRI carried out two months after treatment completion showed minimal residual disease in the uterine cervix, measuring no more than 9 mm in maximum thickness, with near-complete regression of parametrial invasion. However, there was a persistent wide fistula between the uterine cervix, vagina, and urinary bladder through the base. CT of the neck, chest, abdomen, and pelvis showed no distant metastases. Speculum examination at that time showed a residual cervical mass, smaller in size, and a moderate amount of watery discharge. Follow-up PET-CT carried out three months after completion of therapy was compatible with a good metabolic response to therapy, and showed significant regression of the mass and resolution of the hypermetabolic metastatic bilateral external iliac lymph nodes, but a persistent vesicovaginal fistula.

Despite follow-up images and clinical examinations at three-month intervals over the following year, exhibiting a reassuring picture of CR with no local or distant recurrence of cancer, the patient continued to suffer from its consequences, namely, persistent wide vesicovaginal fistula and hydronephrosis. Regarding the former, the patient complained of incontinence, suprapubic pain, dysuria, and hematuria with the passage of blood clots. She sought medical attention at urology and gynecology clinics and was placed on close follow-up. With regard to hydronephrosis, she had bilateral nephrostomies at the time of diagnosis. Her right-sided hydroureteronephrosis resolved five months later, and her right-sided nephrostomy was subsequently removed. However, her left-sided hydroureteronephrosis persisted, and her left-sided nephrostomy required replacement three months after insertion. She also had recurrent UTIs, which necessitated frequent hospitalizations and intravenous antibiotics. The most recent images were taken after 2 years of treatment; MRI showed no evidence of locoregional disease with persistent vesicovaginal fistula, as shown in Figure 2, and a CT scan showed no evidence of distant metastases.

Figure 2 Patient’s most recent pelvic magnetic resonance imaging scan, showing complete resolution of the tumor with no evidence of local disease relapse. A: Axial view; B: Sagittal view; C: Coronal view.

DISCUSSION

The present case highlights the challenging scenario of bulky locally advanced cervical cancer that achieved CR after treatment with CCRT. RT is typically administered as EBRT followed by ICBT boost. However, EBRT boost is a valid option[10]. Large tumor size is an established poor prognostic factor in cervical cancer, and it has been described as the most powerful predictor of disease-specific survival, freedom from disease, pelvic control, and distant metastases[11]. Additionally, tumor volume (TV) is emerging as an important prognostic factor, with one study showing that pre-RT TV > 61.6 cm³ and mid-RT TV > 11.38 cm³ are associated with poorer OS. A TVRR ≤ 82.19% is another independent prognostic factor associated with OS, PFS, and local failure-free survival[9,12], and may be more sensitive than other parameters measured before or after RT13. In our patient, the initial tumor measured 14 cm × 12 cm × 8 cm. Her initial pre-RT TV was 892.2 cm³, while her mid-RT TV (at the time of re-CT simulation after 16 fractions) was 357.2 cm³, exhibiting a TVRR of 60%. The TV at the time of planning for EBRT boost (after 20 fractions of RT) was 130.5 cm, exhibiting a remarkable TVRR of 85.37%. While previous studies have shown CR to CCRT with transverse tumor diameters up to 10.5 cm[13,14], to the best of our knowledge, this is the largest cervical cancer reported in the literature to achieve CR with CCRT.

According to data from the WHO, human papillomavirus (HPV) vaccination is not included in the Jordanian national vaccination schedule, there is no national screening program for cervical cancer, and there are no programs to strengthen early detection of first symptoms at the primary health care level. Moreover, only 12% of women between the ages of 30 and 49 years reported being screened for cervical cancer in 2019, and a recent questionnaire among Jordanian women showed that 91.6% had no idea about the role of HPV vaccination in the prevention of cervical cancer[15]. Hence, it is not far-fetched to postulate that the lack of programs to either screen for or prevent cervical cancer, in addition to a lack of awareness regarding these programs among women, may contribute to late diagnoses and more advanced stages at presentation, as exemplified by our case report.

During treatment, our patient exhibited a dramatic response to CCRT, necessitating the use of adaptive RT. Adaptive RT involves modifying the treatment plan during the course of treatment in response to anatomical changes[16]. It may be online, in which real-time adjustments are made to the plan based on images taken just before the RT session, or offline, in which patients undergo re-CT simulation, re-contouring and re-planning[17]. This allows for improvements in clinical outcomes by improving tumor coverage and reducing treatment toxicity via increased sparing of nearby organs at risk[18]. Studies on other pelvic cancers, such as prostate cancer, have shown that the use of adaptive RT results in a 13% decrease in rectal dose and a 13% increase in minimum prostate dose[19]. One can imagine how adaptive RT is especially useful in gynecological cancers such as cervical cancer, where, as exemplified in our case, tumor size may change significantly over the course of treatment[20], and data on the topic are still evolving. Daily Adaptive EBRT in the Treatment of Carcinoma of the Cervix (ARTIA-Cervix) (clinicaltrials.gov ID: NCT05197881) is an ongoing clinical trial investigating whether the use of adaptive RT for locally advanced cervical cancer will result in decreased toxicity without compromising tumor control.

Although our patient achieved CR through the use of CCRT and became cancer-free, she is still bound by the consequences and complications of her disease that have yet to abate and still affect her quality of life. She continues to suffer from a wide vesicovaginal fistula, which affects her physical and emotional health. Fistula formation is also known to affect social health, as reported in a meta-analysis, in which 36% of women with fistulas were divorced or separated[21]. Management of this complication remains challenging, as existing evidence is inconsistent and no standard guidelines have been established[22,23]. Our patient also suffered from hydronephrosis and still required nephrostomy. Hydronephrosis affects 38% of women with cervical cancer at diagnosis and has a negative impact on OS, even after adjustment for FIGO stage[24,25]. As shown in our case, patients with impaired renal function may also have restrictions on receiving cisplatin during CCRT and remain at an increased risk of toxicity and treatment complications[26].

CONCLUSION

This case demonstrates the potential of CCRT in achieving CR, even in remarkably large cervical tumors, and represents the largest recorded success to date. Despite this, the patient still suffers from serious long-term health consequences, emphasizing the need for early detection and preventive initiatives, particularly in LMIC, which bear the largest brunt of the disease. Concerted efforts are required to address disparities in cervical cancer prevention and improve access to screening programs and HPV vaccinations. Multidisciplinary discussion and care are necessary for optimal treatment, with the role of adaptive RT, in particular, still evolving.