JCOG1202 Subgroup Analysis: Risk Factors for Early Relapse in Patients Undergoing Curative Resection

Relapse after highly invasive surgery for biliary tract cancers (BTCs) causes medical, psychological, social, and economic distress to patients, and it is estimated that 30% of patients with curatively resected BTC will relapse within the first 12 months. Capecitabine has been determined to be the standard of care as adjuvant therapy for patients with BTC who have undergone curative resection; however, no statistically significant difference is seen in overall survival (OS) between capecitabine and observation. An oral fluoropyrimidine derivative, S-1, has demonstrated promising activity in patients with BTC, and adjuvant S-1 has been established as standard of care for patients with resected pancreatic and gastric cancer in Japan. JCOG1202 (UMIN000011688) is a randomized, phase 3 trial that demonstrated OS benefit with adjuvant S-1 in patients with resected BTC. At the 2023 ASCO Gastrointestinal Cancers Symposium, Dr Hiroaki Yanagimoto presented results from a study aimed at investigating the risk factors for early relapse of resected BTCs in the JCOG1202 cohort.

Of 440 patients enrolled in JCOG1202, 217 eligible patients underwent surgery alone (arm A) and 207 eligible patients received adjuvant S-1 (arm B). Early relapse was defined as relapse or death within 12 months after enrollment. Predictive factors for early relapse were assessed using logistic regression analyses in the 424 eligible patients. Of these 424 patients, 97 (22.9%) experienced postoperative early relapse, 59 (27.2%) in arm A and 38 (18.4%) in arm B. Multivariable logistic regression analysis determined that independent risk factors for early relapse included CA 19-9 level >37 U/mL (odds ratio [OR], 2.790; 95% confidence interval [CI], 1.262-6.170; P = .011), poor differentiation (OR, 4.746; 95% CI, 1.927-11.688; P = .0007), moderate differentiation (OR, 1.955; 95% CI, 1.071-3.567; P = .029), >4 lymph node metas-tases (OR, 3.991; 95% CI, 1.674-9.514; P = .0018), 1 to 3 lymph node metastases (OR, 2.661; 95% CI, 1.471-4.814; P = .0012), and presence of residual tumor (OR, 2.171; 95% CI, 1.070-4.408; P = .032). Importantly, adjuvant S-1 chemotherapy significantly reduced early relapse (OR, 0.491; 95% CI, 0.290-0.833; P = .0084). Tumor differentiation, lymph node metastases, perineural invasion, and residual tumor were also considered possible risk factors for early relapse despite S-1 adjuvant therapy.

Postoperative CA 19-9 level, tumor differentiation, lymph node metastases, and residual tumor significantly impact early relapse in patients with curatively resected BTCs. Similar factors are also noted as risk factors in patients receiving adjuvant S-1, suggesting that patients at high risk of early relapse may need more intensive perioperative therapy.

Source: Yanagimoto H, Nakachi K, Ikeda M, et al. Risk factors for early relapse in patients with biliary tract cancers who underwent curative resection: an exploratory subgroup analysis of JCOG1202. Poster presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA. Abstract 541.