Phase II study of organ preservation (OP) in node-negative (NN) low rectal cancer (RC): Updated clinical and patient reported outcomes (PROs).
Authors: Wookey Vanessa , Farma Jeffrey M. , Meyer Joshua E. , Ross Eric A. , Jerome Erika , Singh Tanu , Romasko Ryan , Veggeberg Rosanna , Dotan Efrat , Hall Michael J. , Philp Matthew , Mittal Juhi , Bynum Katrina , Greco Stephanie , Reddy Sanjay S. , Sigurdson Elin R. , Vijayvergia Namrata 
Published: January 2025

148

Background:
Total mesorectal excision (TME) is a highly effective treatment for rectal cancer (RC) but is associated with significant morbidity and mortality. Organ preservation (OP) approaches for locally advanced RC have been successful but not well studied for node-negative (NN) low RC. The objective of this investigator-initiated trial (IIT) is to determine the feasibility of performing successful local excision (LE) after neoadjuvant chemotherapy (CTX) in NN low RC.
Methods:
With IRB approval, patients (pts) with clinical stage T1-3, N0 low rectal adenocarcinomas (<6 cm from anal verge) were included in this single arm phase II IIT. Pts received 6 cycles of FOLFOX (5-FU bolus 400 mg/m2 and infusion 2400 mg/m2, Leucovorin 400 mg/m2, Oxaliplatin 85 mg/m2). Those with evidence of a response underwent LE (transanal excision) 6-12 weeks later. To target occult nodal metastases and reduce in-bowel recurrences, LE was followed by chemoradiotherapy ([CXRT] capecitabine 825 mg/m2 and long course RT to 54 Gy). The primary endpoint was the proportion of pts with successful LE after neoadjuvant CTX (NCT03548961).
Results:
Nineteen pts with low RC were enrolled; nine were female, and the mean age at diagnosis was 65 years. T stage was as follows: T1- 1(5%), T2 - 11(58%), T3 - 7(36%). Eighteen (95%) pts completed at least 5 cycles of neoadjuvant Ctx and 16/19 (84%) underwent LE. Negative margins were achieved in 79% (15/19), meeting our primary endpoint (p < 0.001). Ten (53%) were downstaged, and complete pathological response was achieved in 5/16 (31%) of pts who underwent LE. Four (21%) pts (all T2 stage) did not meet the primary endpoint (3 with inadequate response to CTX and 1 with LE and positive margins). Of these, three were salvaged (2 with CXRT; 1 with TME), and one died of infection (unrelated complication). All 16 who underwent LE completed CXRT. Of the 15 pts with successful OP at a median follow-up of 25.5 months, no local recurrences have been reported and 1 pt with lung nodules below the threshold for metastases at study entry ultimately developed clear lung metastases. Median DFS was not reached. Patient reported outcomes (PRO) assessment revealed a slight decline in physical health scores after neoadjuvant CTX but improved to baseline at follow-up. No decline was seen in mental health scores. Symptom specific QOL (sexual and bowel function) and long-term survival data will be presented.
Conclusions:
Neoadjuvant CTX and LE allows for OP in NN low RC and results in a margin negative LE in over three fourths of pts with durable long term local control and preserved QOL. Ongoing trials are investigating an OP approach in NN RC (NCT03259035). Our approach adds to the mounting evidence and will provide early data of the benefit of adjuvant chemoradiation to target occult nodes in this setting.
Clinical trial information: NCT03548961
.