Prognostic significance of raised serum tumor markers (STM) after 2 cycles of chemotherapy in men with intermediate- and poor-risk non-seminomatous testicular germ cell tumors (NSGCT) treated at a single-centre in India.

Abstract

5036 Background: Testicular GCT is a rare malignancy, with excellent outcomes. However, approximately one-fourth of intermediate risk and half of the patients with poor risk disease succumb to recurrent GCT. We looked at the prognostic significance of raised serum tumor markers after 2 cycles of chemotherapy in patients with poor risk GCT. Methods: This is a chart-review based retrospective analysis of patients with intermediate and poor risk NSGCT diagnosed and treated at a tertiary care centre in New Delhi, India from 2015-2021. Risk categories were defined as per the International Germ Cell Cancer Collaborative Group. Multivariable Cox regression models were constructed to analyse the prognostic impact of normal STM at the end of second cycle of chemotherapy on overall survival (OS) and relapse free survival (RFS), while adjusted for measured confounders. Results: A total of 312 patients were identified with testicular NSGCT, of whom 109 were intermediate (n = 48, 44%) and poor risk (n = 61, 56%). The median age at diagnosis was 27 (interquartile range, 21-34) years. ECOG PS of patients was 0-1 in 51% and 2-4 in 49%, and poor risk patients were more likely to have a poor ECOG PS at diagnosis (70% vs 30%, P < 0.001). First-line chemotherapy was BEP in 86% patients and VIP in the remaining 14%, and surgery for residual disease was performed in 22%. Overall, 35% patients had normal STM after 2 cycles of chemotherapy, and patients with intermediate risk were likely to achieve normal STM at this time-point (50% vs 23%). At a median follow-up of 62 months, the 5-year RFS rate was 62% (poor risk 52% and intermediate risk 78%), and OS rate was 68% (58% and 80%, respectively). Men with normal STM after 2 cycles chemotherapy had a better RFS (hazard ratio [HR], 0.70; 95% confidence interval 0.48-0.81; P < 0.001) and OS (HR,0.82; 95% CI 0.61-0.99; P = 0.04). After adjusting for risk category, and ECOG PS in a multivariable Cox regression model, patients with normal STM at the end of 2 cycles of chemo continued to have better outcomes (adjusted HR for RFS, 0.78; 95% CI, 0.77-0.89; P = 0.03, and adjusted HR for OS, 0.92; 95% CI,0.81-0.99; P = 0.05). Intermediate risk NSGCT and good ECOG PS also predicted better RFS and OS. Conclusions: Patients with NSGCT whose STMs do not normalize after 2 cycles of chemotherapy have worse RFS and OS compared to those with normal STM at this time-point. Further clinical trials will be needed to study the role of escalation or switch of chemotherapy in this subset of population.