Renal Impairment and Late Toxicities Comparing Contemporary Chemotherapy Regimens for Testicular Cancer in a Real-World Setting

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BACKGROUND: This study aimed to quantify, for the first time, cumulative burden of morbidity (CBM) scores-including renal function-in long-term testicular cancer survivors (TCS) treated with contemporary NCCN-endorsed regimens of 4 cycles of etoposide/cisplatin (EPx4) or 3 or 4 cycles of bleomycin/etoposide/cisplatin (BEPx3/BEPx4). PATIENTS AND METHODS: A total of 798 TCS underwent baseline clinical examinations and completed follow-up questionnaires. Severity grades for adverse health outcomes (AHOs) and CBM scores were calculated. Adjusted ordinal logistic regression estimated odds ratios (ORs) for AHOs and CBM scores by treatment regimen. Baseline estimated glomerular filtration rate (eGFR) was analyzed for associations with cumulative cisplatin dose and selected follow-up AHOs. RESULTS: Median age at follow-up was 45 years (median, 11 years postchemotherapy); 516 (65%) TCS survived ≥10 years. Chemotherapy consisted largely of BEPx3 (n=317; 39.7%), EPx4 (n=198; 24.8%), or BEPx4 (n=99; 12.4%); 27 (3.4%) received etoposide/ifosfamide/cisplatin (VIPx4). TCS receiving EPx4 (vs BEPx3) had significantly increased odds of worse renal impairment (adjusted OR [aOR], 1.55; P=.035), ototoxicity (aOR, 1.48; P=.04), and neuropathy (aOR, 1.77; P=.002). Reduced eGFR (<90 mL/min/1.73 m2), observed in 41% of TCS, was associated with cumulative cisplatin dose (r = -0.149; P<.0001) and with 2- to 20-fold increased odds of developing hypertension (60-89 mL/min/1.73 m2: OR, 2.01; P=.001; 45-59 mL/min/1.73 m2: OR, 2.84; P=.040; 30-44 mL/min/1.73 m2: OR, 20.0; P=.001). Moderate-to-severe eGFR reductions (30-44 mL/min/1.73 m2) were also associated with significantly increased odds of developing hyperlipidemia (OR, 6.10; P=.032) and/or cardiovascular disease (CVD) (OR, 7.09; P=.023). Significantly increased odds of Raynaud phenomenon were associated with β-blocker use (OR, 2.17; P=.036), peripheral artery disease (OR, 3.14; P=.002), reduced eGFR (OR per 10 mL/min/1.73 m2 increase in eGFR, 0.90; P=.027), and BEPx4 (OR vs EPx4, 2.18; P=.003). CBM scores were similar after EPx4 compared with BEPx3 (aOR, 1.04; P=.83) but worse after BEPx4 (aOR, 1.77; P=.016) or VIPx4 (aOR, 2.24; P=.038). Self-reported global physical health correlated strongly with CBM score (P<.001) and chemotherapy regimen (P<.001). CONCLUSIONS: This multicenter, real-world study shows that long-term CBM scores after NCCN-endorsed EPx4 or BEPx3 are comparable, but statistically significant differences in cisplatin-related toxicities exist. Cisplatin dose-dependent reductions in eGFR are followed by significant excesses of hypertension, hyperlipidemia, and CVD.

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