Long-term effects on renal function, cardiovascular risk, and overall health burden in survivors of testicular cancer differed according to the chemotherapy regimen each patient received, according to the results of a large real-world study published in JNCCN—Journal of the National Comprehensive Cancer Network.
“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 corresponding author Sarah L. Kerns, PhD, MPH, 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.”
Background and Study Methods
Researchers wanted to assess the long-term health effects of survivors of testicular cancer in those who received contemporary chemotherapy regimens. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)-recommended contemporary chemotherapy regimens in this setting included four cycles of etoposide/cisplatin or three/four cycles of bleomycin/etoposide/cisplatin. The investigators focused especially on the impact on cumulative burden of morbidity and renal function.
The study included 798 survivors of testicular cancer who were treated at eight major cancer centers in North America and calculated severity grades for adverse health outcomes and their cumulative burden of morbidity scores by treatment regimen.
Key Findings
Sixty-five percent of the particiapants survived 10 years or more. The most common chemotherapy regimen in the group was three cycles of bleomycin/etoposide/cisplatin (39.7%) followed by four cycles of etoposide/cisplatin (24.8%).
Survivors who had received etoposide/cisplatin for four cycles were the most likely to have worse renal impairment (adjusted odds ratio [aOR] = 1.55; P = .035), ototoxicity (aOR = 1.48; P = .04), and neuropathy (aOR = 1.77; P = .002).
Reduced estimated glomerular filtration rates (41%) were associated with cumulative cisplatin doses (P < .0001), and these patients had a greater risk of developing hypertension. In survivors with more moderate-to-severe reductions in estimated glomerular filtration rates also had a greater risk of developing hyperlipidemia (OR = 6.10; P = .032) and/or cardiovascular disease (OR = 7.09; P = .023).
A risk for Raynaud phenomenon was also increased in survivors who used beta-blockers (OR = 2.17; P = .046), those with peripheral artery disease (OR = 3.14; P = .002), reduced estimated glomerular filtration rates (P = .027), and in those who received four cycles of bleomycin/etoposide/cisplatin (OR = 2.18; P = .003).
“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 senior author Lois B. Travis, MD, ScD, 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.”
Cumulative burden of morbidity scores were similar with four cycles of etoposide/cisplatin as with three cycles of bleomycin/etoposide/cisplatin (aOR = 1.04; P = .83), but was worse for those treated with four cycles of bleomycin/etoposide/cisplatin (aOR = 1.77; P = .016).
Self reports for global physical health showed a strong correlation with cumulative burden of morbidity scores (P < .001) and chemotherapy regimen (P < .001).
DISCLOSURE: This research was part of the multi-center Platinum Study which was supported by the National Cancer Institute. For full disclosures of the study authors, visit jnccn.org.
