Neoadjuvant chemotherapy and surgery for rectal cancer: Omission of radiation in clinical practice.

3595 Background: PROSPECT proved efficacy of induction chemotherapy and surgery, without radiation, for select stage II and III rectal cancer patients with improvements in bowel function and less diverting ileostomy. This approach also avoids radiation-associated alteration in fertility which is particularly important in the rising early onset population. In this study we review our broader current use of induction chemotherapy without radiation in locally advanced rectal cancer patients. Methods: Review of a prospectively maintained IRB approved, institutional database for patients treated with induction chemotherapy and surgery between 2015-2024. Clinicopathologic features are summarized, and disease-free survival (DFS) measured with the Kaplan-Meier method. Results: A total of 171 patients, median age 50 years (IQR 43-61), were identified with tumors located ≤5cm (n = 4, 2.3%), 6-10cm (n = 75, 44%), and 11-15cm (n = 92, 54%) from the anal verge. Pre-treatment MRI staging was available for 169/171 patients. 2 (1.2%) and 167 (99%) were MRI stage II and III including 23 with T4 lesions, 15 with extra-TME lymph nodes, and 28 with EMVI. Neoadjuvant chemotherapy regimens included CAPEOX (n = 71, 42%), FOLFOX (n = 98, 57%), and FOLFIRINOX (n = 2, 1.2%). 166 (97%) underwent low anterior resection with (n = 94, 57%) or without (n = 72, 43%) diverting ileostomy, 4 (2.3%) underwent abdominoperineal resection (APR), and 1 (0.6%) underwent a Hartmann procedure. Pathologic responses included: 28 (16%) AJCC TRG 0 (no viable cancer cells); 32 (19%) TRG 1 (small cluster/single cancer cells); 77 (45%) TRG 2 (residual cancer with predominant fibrosis); and 34 (20%) TRG 3 (extensive residual cancer). Tumor deposits were present in 24 (14%) and positive/close margin was noted in 2 (1.2%). With a median follow-up of 24 months, 4 (2.3%) patients developed local recurrence (salvaged with chemotherapy, radiation, and surgery) and 18 (11%) developed distant metastases. 1-year DFS was 92% (CI: 88-97) and 2-year DFS was 87% (CI: 81-93). Conclusions: Since PROSPECT, induction chemotherapy and surgery is being offered to higher risk rectal cancer patients, including those with T4 lesions and EMVI, with favorable results. Continued individualized care based on response to chemotherapy and omission of radiation can limit treatment related toxicity while maintaining excellent oncologic outcome.