ABSTRACT
Background: Interest in organ preservation (OP) strategies for rectal cancer (RC) patients persists. The efficacy of long course chemoradiation (LCRT) vs. short course radiation therapy (SCRT) relative to OP is unknown. We compared OP rates between SCRT and LCRT total neoadjuvant therapy (TNT) strategies. Method(s): During the COVID-19 pandemic we established an institutional SCRT mandate with no exceptions. For comparison, we identified RC patients treated with LCRT immediately before and after the mandate period. After completion of TNT, patients were restaged by clinical exam, endoscopy, and MRI. A watch and wait (WW) approach was recommended for patients with a clinical complete response (cCR), defined by the MSK regression schema. Total mesorectal excision (TME) was recommended for non-cCR patients. OP was defined as alive, TME-free, and with no evidence of disease in the pelvis. We performed survival analysis for: local regrowth rate, OP, disease-free survival (DFS), and overall survival (OS). Result(s): We identified 563 consecutive patients with RC treated with TNT, of whom 231 were excluded due to either metastatic disease, synchronous/metachronous malignancies, or non-adenocarcinoma histology (Jan. 2018-Jan. 2021). Patient and tumor characteristics were similar in the LCRT (n = 256) and SCRT (n = 76) cohorts. No significant differences in high-risk features were noted. Most patients had clinical stage III disease (82% in LCRT vs. 83% in SCRT). Induction chemotherapy followed by consolidative radiation was the most common treatment order (78% (LCRT) vs. 70% (SCRT)). The median interval from end of TNT to clinical restaging was 8 weeks (LCRT) and 9 weeks (SCRT). The cCR rate was 46% in both cohorts. The cCR rate was numerically higher in patients treated with radiation first, as compared to chemotherapy first (53% vs. 44% (LCRT) and 52% vs. 43% (SCRT)). Among patients with a cCR, the likelihood of WW management was similar (98% (LCRT) vs. 94% (SCRT)). From start of TNT, the median follow-up was 32 and 28 months respectively for LCRT and SCRT. The 2-year OS (95% vs. 92%), DFS (78% vs 70%), and distant recurrence (20% vs. 21%) rates were similar. Among all patients, the 2-year OP rate was 40% (95% CI 35-47%) for LCRT and 29% (95% CI 20-42%) with SCRT. In those patients managed by WW, the 2-year local regrowth rate was 20% (95% CI 12-27%) with LCRT vs. 36% (95% CI 16-52%) with SCRT. Conclusion(s): In this nonrandomized comparison, while cCR rates were similar, we observed a numerically higher OP rate with LCRT-TNT than with SCRT-TNT. The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that LCRT-TNT will increase OP rates relative to SCRT-TNT, should definitively answer this question.
ABSTRACT
Purpose/Objective(s): While long course chemoradiation therapy has been studied as part of a watch-and-wait (WW) strategy for patients with locally advanced rectal cancer, it is unclear whether short-course radiation therapy (SCRT) will be associated with similar rates of organ preservation. We hypothesized that a WW strategy to facilitate organ preservation with SCRT, as part of a total neoadjuvant therapy (TNT) approach during the COVID-19 pandemic, would be both safe and feasible. Materials/Methods: From March to June of 2020, due to the COVID-19 pandemic, per institutional policy, all patients undergoing radiation therapy for locally advanced rectal cancer were treated with SCRT. After completion of SCRT-TNT, patients were clinically restaged by exam, endoscopy and MRI and the decision was made to manage the patient surgically or with a WW approach. The decision for WW or surgery was made by the surgeon in conjunction with patient consent. After IRB waiver was obtained, we reviewed consecutive patients treated during our SCRT mandate. The main outcome of interest was total mesorectal excision (TME)-free survival among patients eligible for WW after SCRT-TNT. Results: Our cohort included 42 patients with a median age of 57 years (Interquartile Range [IQR] 48-67), 24 (57%) of whom were male. Median follow-up from end of SCRT-TNT was 7 months (IQR 6-8). The median tumor cranio-caudal size was 4.1 cm (IQR 3.3-5.2) with a median distance from the anal verge of 7 cm (IQR 5-9). The majority had cT3 (71%) or cN+ (74%) disease. Patients underwent a median of 14 weeks (IQR 13-15) of FOLFOX or CAPEOX chemotherapy, with 32 (76%) patients receiving chemotherapy prior to SCRT and 10 (24%) patients receiving chemotherapy after SCRT. The median time from completion of TNT to endoscopic restaging was 9 weeks (IQR 7-10). Nineteen (45%) patients were recommended to undergo surgical resection, of whom 17 went on to TME and 2 refused TME. Of the 15 patients with pathology available, 2 had a pCR (13%). Notably, one of these patients had a cCR at post-TNT endoscopy, but due to the presence of a stricture, WW was deemed unfeasible. Of the 23 patients managed by a WW strategy after SCRT-TNT completion, 19 had a clinical complete response (cCR), 3 had a near-CR, and 1 had an incomplete response. The 6-month TME-free survival was 85% for patients on WW. Four (17%) patients had a local regrowth at a median of 20 weeks (IQR 17-24), 3 of whom were salvaged with TME and 1 who declined surgery and opted for further surveillance. One of these patients had regrowth confirmed by biopsy, but had a pCR confirmed in the TME specimen. The 6-month TME- free survival of the entire cohort was 52%, and the combined pCR/6-month cCR was 52%. Conclusion: Our data suggest WW after SCRT-TNT is feasible. Longer term follow-up is required to confirm the durability and oncologic safety of these results.