EP362 - Management Strategies And Non-Operative Approaches In Metastatic Rectal Cancer Patients Achieving Complete Clinical Response: A Systematic Review

Purpose/Background: While the concept of watch and wait (WW) following neoadjuvant therapy is well characterized in locally advanced rectal cancer, its role in metastatic rectal cancer (mRC) remains poorly defined. As systemic and locoregional treatments improve, a subset of patients with mRC may achieve a clinical complete response (cCR) of the primary tumor, raising questions about the role of WW in these patients. This systematic review aims to evaluate management strategies and outcomes among mRC patients achieving cCR after neoadjuvant therapy.

Methods/Interventions: We conducted a systematic search in PubMed, Embase, Web of Science, and CENTRAL, identifying studies reporting mRC patients who achieved cCR following neoadjuvant therapy. Two independent reviewers screened abstracts and performed full-text review. Extracted data included study design, patient demographics, neoadjuvant regimens, metastatic sites, cCR definitions, post-cCR management strategies, and oncologic outcomes. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies.

Results/Outcomes: A total of 11 studies from 2004-2025 were included (mRC subset n=646 patients). The most common metastatic sites reported across all studies were to the liver and lung. Neoadjuvant regimens included FOLFOX, CAPOX, bevacizumab, cetuximab, and pelvic radiotherapy (short-course 25Gy/5fx or long-course ~50Gy/25fx). The cCR rate ranged from 0.78% to 81% across studies. Tumor location data, when reported, showed median distance from anal verge ranging from 5.2-7.2 cm, predominantly involving low and middle rectum. Management strategies following cCR were heterogeneous: 52.2% (n=337) underwent surgical resection, 9.9% (n=64) pursued WW protocols, 35.0% (n=226) continued systemic therapy or chemoradiotherapy, and 2.9% (n=19) transitioned to palliative care alone.

Among patients who underwent WW protocols, with available follow up data (n=52), the weighted average local regrowth rate was 40.4%, with rates ranging from 11% to 50%, while distant progression occurred in up to 59.5% of patients. Median overall survival in WW cohorts was 35 months vs 28.3 months in surgically managed patients. Rationale for non-operative management included organ preservation, quality of life optimization, and avoidance of total mesorectal excision-related morbidity, including low anterior resection syndrome and permanent stoma. Palliative-intent cohorts showed inferior survival outcomes compared to curative-intent groups regardless of operative approach.

Conclusion/Discussion: Among mRC patients achieving cCR after neoadjuvant therapy, management strategies remain heterogeneous. Non-operative management appears feasible in carefully selected patients and may offer comparable survival to surgical resection while preserving organ function and quality of life. However, the observed survival differences may reflect tumor biology, as less aggressive tumors are more likely to achieve cCR and thus enter non-operative pathways, introducing potential selection bias. Surprisingly, local regrowth rates in mRC are only moderately higher than reported rates in non-metastatic WW cohorts. These findings suggest a potential paradigm shift toward individualized, response-based treatment algorithms in mRC. Prospective multicenter studies are needed to define selection criteria, surveillance protocols, and survival implications of WW in this population.

PRISMA Flow Diagram Outlining Selection of Studies
PRISMA Flow Diagram Outlining Selection of Studies