Current and future perspectives in the management and treatment of colorectal cancer

Table 1 Treatment options for resectable colorectal cancer

Treatment modality	Description	Additional comments
Surgery	Laparoscopic surgery, robotic surgery and navigation surgery	Laparoscopic surgery: Reduced infection risk compared to open surgery; Robotic surgery: Improved precision, dexterity, lymph node dissection; Navigation surgery: Real-time blood flow visualization, useful for lymph node mapping
Radiotherapy in resectable patients	Adaptive radiotherapy adjusts treatment in real time; Image-guided radiotherapy; Volumetric arc modulation; Intraoperative radiotherapy; Magnetic resonance-guided radiotherapy	Modalities used for tumor reduction and preoperative microscopic disease in resectable rectal cancer; Advanced techniques improve precision and minimize toxicities
Total neoadjuvant therapy	Combines radiotherapy and preoperative chemotherapy to improve local control and reduce the risk of metastasis	Indicated for locally advanced rectal cancer (cT3, cT4 or N +); It improves the rate of complete pathological response and can avoid surgery in selected cases with complete response, favoring wait and see
Adjuvant chemotherapy	Indicated in high-risk stages II and in stages III after surgery; Fluoropyrimidines + oxaliplatin	Improves disease-free survival by eliminating residual tumor cells; Sequentially in postoperative treatment is key to reducing the risk of recurrence
Immunotherapy	Currently under investigation for locally advanced MSI-H/dMMR cancer in the neoadjuvant setting	Pembrolizumab and nivolumab are being studied in clinical trials but are not used as standard in resectable non-MSI-H/dMMR disease
Circulating tumor DNA	Biomarker used to detect minimal residual disease after curative treatment	It helps to identify patients at high risk of relapse and decide on the use of adjuvant chemotherapy after surgery

MSI-H/dMMR: High microsatellite instability/deficient mismatch repair.

Table 2 Treatment options for metastatic colorectal cancer

Treatment modality	Description	Additional comments
Surgery	Indicated for resection of resectable liver, lung or peritoneal metastases	Combined with neoadjuvant or adjuvant chemotherapy in patients with good performance status
Systemic chemotherapy	Indicated in metastatic disease as part of a sequential approach, combined with or without biological agents	It is essential to control metastatic disease, regardless of the site of the metastases
Adaptive radiation therapy	It offers the ability to adjust treatment in real time using magnetic resonance imaging to improve precision	Indicated for oligometastases or metastases in the liver and lung
Image-guided radiotherapy and volumetric modulation techniques	It allows for greater precision in dosing	Used in patients with metastases in specific sites (liver, lung) who are not candidates for surgery
Stereotactic radiotherapy	Indicated for the treatment of oligometastatic metastases in the liver, lung, and bones	Non-invasive and precise technique for symptom control or to prolong survival
Targeted therapies EGFR (cetuximab)	Indicated in RAS wild-type metastatic tumors in combination with chemotherapy	Requires confirmation of RAS mutational status and molecular evaluation of the tumor
Targeted therapies VEGF (bevacizumab)	Indicated in metastatic colorectal cancer, regardless of mutational status, in combination with chemotherapy	Blocks tumor angiogenesis to improve the outcomes of systemic treatment
Targeted therapy BRAF (encorafenib)	Indicated for patients with BRAF-V600E mutation in combination with cetuximab for metastatic colorectal cancer	Used after progression on prior chemotherapy
Targeted therapy HER2 (trastuzumab)	Indicated for patients with HER2-positive, RAS wild-type metastatic colorectal cancer that does not respond to standard chemotherapy	Used in combination with tucatinib
Checkpoint inhibitors	Pembrolizumab, nivolumab, ipilimumab are indicated in metastatic cancer with MSI-H or dMMR	Effective in patients with high microsatellite instability, but not in pMMR/MSS tumors

dMMR: Mismatch repair deficiency; EGFR: Epidermal growth factor receptor; HER2: Human epidermal growth factor receptor 2; MSI-H: High microsatellite instability; MSS: Microsatellite stable; pMMR: Proficient mismatch repair; RAS: Rat sarcoma protein family; VEGF: Vascular endothelial growth factor.