Survival outcomes of adjuvant treatment in upstaged clinical T2N0 rectal cancer: are we underutilizing therapy?

Background: Patients with rectal cancer staged as clinical T2N0 (cT2N0) are recommended to undergo upfront resection. However, when the tumor is subsequently upstaged to pathologic T3N0 (pT3N0), there are no clear guidelines for adjuvant treatment. This study aimed to analyze national trends in adjuvant management and to identify differences in morbidity or survival.

Methods: Using the National Cancer Database (2004-2020), adult patients with cT2N0 rectal adenocarcinoma that were upstaged to pT3N0 after resection were identified. The treatment groups included (i) surgery alone, (ii) surgery + postoperative (post-op) chemotherapy alone, (iii) surgery + post-op chemoradiation (CRT), and (iv) surgery + chemotherapy + CRT. Cox proportional hazard models and Kaplan-Meier curves (6-month landmark analysis) were used to compare survival outcomes.

Results: The analytic cohort included 800 patients who received the following treatments: surgery alone (496 [60%]), surgery + post-op chemotherapy (139 [17%]), surgery + post-op CRT (137 [15%]), and surgery + chemotherapy + CRT (69 [8%]). Patients who underwent post-op chemotherapy or chemotherapy + CRT had higher rates of poor/undifferentiated tumors (15.7% and 15.4%, respectively) than those who underwent surgery alone (8.8%) (P = .047). Over the study period, surgery alone decreased from 86.7% to 65.6%, with concomitant increases in post-op adjuvant therapy. Post-op chemotherapy (hazard ratio [HR], 0.336; 95% CI, 0.196-0.575) and chemotherapy + CRT (HR, 0.447; 95% CI, 0.231-0.866) remained independently associated with improved overall survival. Of note, 5-year survival was the lowest in the surgery-alone group (62.5%).

Conclusion: Post-op adjuvant regimens, including chemotherapy, were independently associated with improved survival in patients with cT2N0 rectal cancer upstaged to pT3N0. Adjuvant therapy may be underutilized in this setting.