Expert Perspectives on Balancing Therapy Decisions and Quality of Life in mCRC

Single-agent therapies and immunotherapy approaches do not automatically guarantee superior quality of life compared to combination chemotherapy regimens, as treatment tolerability depends heavily on individual patient experiences and specific toxicity profiles. While oral therapies and simplified administration schedules offer convenience advantages, patients may still experience significant quality-impacting adverse effects such as severe itching, rash, or fatigue that substantially affect daily functioning. The universal patient preference for immunotherapy over traditional chemotherapy in microsatellite instability-high (MSI-high) colorectal cancer (CRC) demonstrates clear quality of life benefits when treatments are well-matched to tumor characteristics.

The management of Lynch syndrome patients has evolved with the introduction of effective immunotherapy options, raising important questions about the necessity of prophylactic surgical interventions. While immunotherapy provides excellent disease control in MSI-high tumors, current evidence does not support reducing surveillance requirements for patients with Lynch syndrome, as immunotherapy may not prevent future Lynch-related cancers. The decision regarding prophylactic subtotal colectomy now involves more complex discussions balancing surgical morbidity against long-term cancer risk.

Neoadjuvant immunotherapy has enabled organ preservation strategies, particularly in patients with rectal cancer with Lynch syndrome who achieve complete responses and can be managed with nonoperative approaches. However, this requires intensive surveillance protocols that may actually exceed the monitoring needed after surgical resection. The quality of life implications of prophylactic surgery, including increased bowel frequency and dietary restrictions, must be weighed against individual patient risk tolerance and preferences in comprehensive shared decision-making discussions.