Giulia Capelli1, Irene De Simone2, Gaya Spolverato3, Michela Cinquini2, Ivan Moschetti2, Sara Lonardi4, Gianluca Masi5, Chiara Carlomagno6, Domenico Corsi7, Gabriele Luppi8, Maria Antonietta Gambacorta9, Francesca Valvo10, Renato Cannizzaro11, Federica Grillo12, Brunella Barbaro9, Angelo Restivo13, Marco Messina14, Alessandro Pastorino15, Carlo Aschele15, Salvatore Pucciarelli15. 1. Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Via Giustiniani 2, 35121, Padua, Italy. 2. Mario Negri Institute for Pharmacological Research, IRCCS, Milan, Italy. 3. Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Via Giustiniani 2, 35121, Padua, Italy. gaya.spolverato@unipd.it. 4. Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy. 5. University Hospital of Pisa, Pisa, Italy. 6. "Federico II" University of Napoli, Naples, Italy. 7. San Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy. 8. University Hospital of Modena, Modena, Italy. 9. Agostino Gemelli Hospital, Rome, Italy. 10. CNAO (Centro Nazionale di Adroterapia Oncologica) Foundation, Pavia, Italy. 11. CRO (Centro di Riferimento Oncologico) IRCCS, Aviano, Italy. 12. S. Martino University Hospital, IRCCS, Genoa, Italy. 13. Department of Surgical Sciences, University of Cagliari, Cagliari, Italy. 14. San Raffale Giglio Hospital, Cefalù, Palermo, Italy. 15. Sant'Andrea Hospital, La Spezia, Italy.
Abstract
BACKGROUND: The standard approach for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). After nCRT 20% of patients achieve a clinical complete response (pCR) and could be treated with a non-operative management (NOM). METHODS: The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on rectal cancer applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach addressing the following question: Should NOM vs. TME be used for patients with rectal cancer with clinical complete response after nCRT? Five outcomes were identified: disease-free survival (DFS), mortality, local recurrence, colostomy rate, and functional outcomes. RESULTS: Nine studies were included in the analysis. A higher risk of disease recurrence was observed in the NOM group compared to the TME group (RR = 1.69, 95% CI 1.08, 2.64) on the other hand, we observed a slightly positive but not significant effect on mortality of NOM (RR = 0.82, 95% CI 0.46, 1.45). Patients in the NOM group were more likely to experience local recurrence (RR = 5.37, 95% CI 2.56, 11.27) and patients in the TME group were more likely to have a permanent colostomy (RR = 0.15, 95% CI 0.08, 0.29). Only one study evaluated functional outcomes. The overall certainty of evidence was rated as very low. CONCLUSIONS: NOM was found to correlate with a higher risk of local recurrence which did not translate in worse OS and a lower colostomy rate. Due to the paucity of evidences, no recommendations are possible. NOM remains an experimental treatment; thus, patients managed with NOM should be enrolled in clinical trials with a dedicated follow-up schedule.
BACKGROUND: The standard approach for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). After nCRT 20% of patients achieve a clinical complete response (pCR) and could be treated with a non-operative management (NOM). METHODS: The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on rectal cancer applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach addressing the following question: Should NOM vs. TME be used for patients with rectal cancer with clinical complete response after nCRT? Five outcomes were identified: disease-free survival (DFS), mortality, local recurrence, colostomy rate, and functional outcomes. RESULTS: Nine studies were included in the analysis. A higher risk of disease recurrence was observed in the NOM group compared to the TME group (RR = 1.69, 95% CI 1.08, 2.64) on the other hand, we observed a slightly positive but not significant effect on mortality of NOM (RR = 0.82, 95% CI 0.46, 1.45). Patients in the NOM group were more likely to experience local recurrence (RR = 5.37, 95% CI 2.56, 11.27) and patients in the TME group were more likely to have a permanent colostomy (RR = 0.15, 95% CI 0.08, 0.29). Only one study evaluated functional outcomes. The overall certainty of evidence was rated as very low. CONCLUSIONS: NOM was found to correlate with a higher risk of local recurrence which did not translate in worse OS and a lower colostomy rate. Due to the paucity of evidences, no recommendations are possible. NOM remains an experimental treatment; thus, patients managed with NOM should be enrolled in clinical trials with a dedicated follow-up schedule.
Entities:
Keywords:
GRADE; Metanalysis; Neoadjuvant chemotherapy; Rectal cancer; Surgery