Study identifies long-term health risks in testicular cancer survivors treated with contemporary chemotherapy

A large, multi-center study published online in the Journal of the National Comprehensive Cancer Network (JNCCN) provides new insight into the long-term health effects of contemporary chemotherapy regimens used to treat testicular cancer, highlighting differences in renal function, cardiovascular risk, and the overall burden of chronic health conditions among survivors.

It’s expected these study findings will be used to inform national follow-up guidelines for cisplatin-treated testicular cancer survivors in the future.

Testicular cancer is the most common cancer in young men aged 18–39, and modern cisplatin-based chemotherapy cures more than 95% of patients. However, as survival has improved, attention has increasingly shifted to the long-term health consequences faced by testicular cancer survivors who may live for many decades after completing treatment.

In the largest real-world study to date comparing contemporary National Comprehensive Cancer Network (NCCN)-recommended chemotherapy regimens, researchers evaluated nearly 800 long-term testicular cancer survivors treated at eight major cancer centers in North America. The study assessed a broad range of adverse health outcomes and quantified survivors’ cumulative burden of morbidity more than a decade after treatment.

“Our findings show that while today’s standard chemotherapy regimens are highly effective at curing testicular cancer, they’re associated with meaningful long-term health risks that appear to differ by treatment approach,” said Sarah L. Kerns, Ph.D., MPH, corresponding author and associate professor of radiation oncology at the Medical College of Wisconsin.

“Understanding these differences allows clinicians and patients to make more informed decisions and emphasizes the importance of long-term survivorship care.”

The study found that testicular cancer survivors treated with four cycles of etoposide and cisplatin (EPx4) had significantly higher odds of renal impairment, hearing loss, and peripheral neuropathy compared with those treated with three cycles of bleomycin, etoposide, and cisplatin (BEPx3).

Nearly 41% of all survivors in the study showed some degree of at least mild renal dysfunction, which was strongly associated with the cumulative cisplatin dose.

Importantly, reduced renal function was linked to higher risks of developing hypertension, high cholesterol, and cardiovascular disease later in life—conditions that can significantly impact long-term quality of life and survival.

“This study demonstrates for the first time that even mild reductions in renal function after chemotherapy can signal elevated later cardiovascular risk in testicular cancer survivors,” said Lois B. Travis, MD, ScD, senior author and the Lawrence H. Einhorn Professor of Cancer Research at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center.

“These findings underscore the need for lifelong monitoring of both renal and cardiovascular health in this young survivor population.”

Researchers also found that the overall cumulative burden of morbidity—a measure that captures both the number and severity of chronic health conditions—was similar between EPx4 and BEPx3, but significantly worse among survivors who received more intensive regimens. Worse morbidity scores were closely linked to poorer self-reported physical health, reinforcing the clinical relevance of these long-term effects.

Because the health conditions identified in the study are often detectable through routine clinical evaluations, the authors emphasize that many of the risks can be identified early and potentially mitigated through targeted surveillance, lifestyle interventions, and preventive care.

The study was conducted as part of the multi-center Platinum Study.