Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study

Abstract

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT.

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature

“…The role of dostarlimab, another antiPD-1 checkpoint inhibitor, as neoadjuvant treatment in locally advanced rectal cancer also showed a remarkable 100% clinical complete response (cCR), allowing these patients to spare chemoradiotherapy and surgery, with no relapse evidence during follow up. These results have been confirmed in a 20-patient retrospective study: a 90% cCR was observed and pCR was confirmed in all the 11 patients that underwent surgery; the other 7 patients chose a watch-and-wait strategy, with no local or distant recurrence observed in neither of the groups ( 28 ). Interestingly, none of these trials are evaluating the role of immunotherapy as conversion therapy in oligometastatic disease and data from patients that could be elected for surgery in the metastatic trials published were censored.…”

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer

“…The multicenter cohort study by Yang et al investigated the management of dMMR or MSI-H LARC following neoadjuvant anti-PD-1 monotherapy, exploring the possibility of avoiding surgery in the case of cCR [34]. In fact, 7 of 20 enrolled patients with cCR adopted a W&W strategy.…”

Radiotherapy in the preoperative neoadjuvant treatment of locally advanced rectal cancer

“…Considering the remarkable efficacy of immunotherapy in colorectal cancer, at the 2022 ASCO Annual Meeting, Cercek et al demonstrated that a 100% cCR rate could be achieved with dostarlimab alone for patients with dMMR/MSI-H (115). Additionally, Yang et al used different types of PD-1 inhibitors, including pembrolizumab, sintilimab, and tislelizumab, to treat 20 LARC patients with dMMR/MSI-H. As a result, 90% of the patients experienced CR, of whom 11 achieved pCR postoperatively, and the remaining 7 had cCR or near-cCR, with 2year DFS and OS rates of 100% (116). Further, Chen et al found that 12 out of the 16 patients in their study achieved CR, further demonstrating the significant efficacy of immuno-monotherapy as a neoadjuvant treatment for LARC patients with dMMR/MSI-H (117).…”