RETHINKING CHEMOTHERAPY TIMING IN STAGE II NSGCT: BALANCING SURVIVAL AND MINIMIZING TOXICITY

Abstract

Introduction

Adjuvant treatment of stage II nonseminomatous germ cell tumors (NSGCT) following retroperitoneal lymph node dissection (RPLND) requires careful consideration of the risks and benefits of adjuvant versus salvage systemic therapy. While early adjuvant chemotherapy improves recurrence-free survival, its impact on overall survival compared to treatment in the salvage setting is disputed.

Methods

Patients with tumor marker-negative clinical stage II NSGCT (T_ANYN_1-3M₀S₀) were identified within the NCDB testis cancer dataset from 2004 to 2021. Inclusion criteria were patients who underwent RPLND, had confirmed nodal disease on final pathological staging, and received postoperative chemotherapy. Mean time to chemotherapy by pathological nodal stage was compared using an analysis of variance (ANOVA) with post-hoc pairwise t-tests. A multivariable Cox proportional hazards regression model, incorporating patient comorbidities, tumor characteristics, and an interaction term for chemotherapy receipt at any time, was used to assess overall survival stratified by pathologic nodal stage.

Results

A total of 186 patients with marker-negative clinical stage II disease who underwent RPLND with pathologically confirmed nodal disease were identified. Patient demographics, presented in Table 1, show nominal differences in patient characteristics and general concordance between clinical and pathological nodal staging. Figure 1A indicates a trend towards earlier chemotherapy for patients with pN3 disease (median 7.5 weeks) compared to those with pN1 (11.2 weeks) and pN2 disease (10.2 weeks), although this did not reach statistical significance (p=0.056). With a median follow-up of 86 months, mortality was rare, occurring in only 7 patients (3 pN1, 2 pN2, 2 pN3). The 10-year overall survival curves showed no significant difference (Figure 1B), and early chemotherapy timing did not predict survival (HR 0.99, 95% CI 0.87-1.135) when accounting for chemotherapy receipt at any time.

Conclusions

The timing of chemotherapy does not appear to impact overall survival in patients when controlling for chemotherapy receipt at any time. Therefore, a delay in administration of systemic therapy following RPLND, in this patient population at high risk for developing chemotherapy-associated adverse effects, should be considered. Further research is needed to determine the impact on specific high-risk populations, such as patients with pN3 disease, who were underrepresented in this study.