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PURPOSE Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.