Addressing Cisplatin's Late Effects in Testicular Cancer Survivors

New research shows that survivors of testicular cancer may have an increased burden of morbidity after being treated with cisplatin-based chemotherapy, with obesity, neuropathies, and tinnitus and hearing loss among the most prevalent late effects.

Sarah L. Kerns, PhD, MPH

New research shows that survivors of testicular cancer may have an increased burden of morbidity after being treated with cisplatin-based chemotherapy, with obesity, neuropathies, and tinnitus and hearing loss among the most prevalent late effects.

Burden of morbidity also increased with age and had a negative impact on self-perception of health, according to a study presented by Sarah L. Kerns, PhD, MPH, at the 2016 Cancer Survivorship Symposium in San Francisco.

Most men with testicular cancer are diagnosed at a young age, and while the disease is highly curable with a 10-year survival rate of more than 95%, this population is vulnerable to future health conditions.

“Despite this excellent long-term survival profile, testicular cancer survivors are at risk for late adverse effects from treatment for many decades—most of their adult life,” said Kerns, a research assistant professor in the Department of Radiation Oncology at University of Rochester Medical Center.

“This really represents an important population in which to study late effects of cancer, in particular, cisplatin-based chemotherapy effects on health outcomes.”

The study evaluated 751 participants under age 50 at the time of their diagnosis who underwent cisplatin-based chemotherapy.

The survivors answered questionnaires about health outcomes and prescription drug use. Outcomes were mapped and graded for severity using the the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 0 was categorized as no adverse effects, and grade 4 was the most severe.

Obesity was the most commonly reported health outcome (74%), followed by peripheral sensory neuropathy (63%), peripheral motor neuropathy (45%), tinnitus (45%), hearing loss (44%), and erectile dysfunction (29%).

“Obesity was by far the most frequent, and this likely reflects national trends in obesity rates in the United States as well as the effects of cisplatin, which is known to affect symptoms of metabolic syndrome,” Kerns said.

Considering the frequency and severity of each outcome, a cumulative burden of morbidity (CBM) was then derived.

Nearly 70% of testicular cancer survivors had a CBM score of medium, which was defined as at least one grade 2 health outcome or one grade 3 outcome. Twenty percent of survivors had a high CBM, defined by multiple grade 3 outcomes.

Only 2.5% reported having no adverse health outcomes, 8.3% had at least one grade 1 outcome, and 0.5% had a severe CBM score.

The findings showed that an increase in number and severity of health outcomes contributed to an increased CBM score. In addition, older age was associated with increased odds of having a worse CBM score, and an increasing CBM score showed a negative impact on self-perceived health (OR = 2.56, 95% CI 2.03-3.2; P < .001).

The authors noted that this finding shows that survivors perceive health conditions following chemotherapy as negatively impacting their health in survivorship.

Of the participants, 62.5% received bleomycin, etoposide, and cisplatin (BEP), and about one-third received etoposide and cisplatin (EP).

Each 100 mg/m2 increase in cisplatin was associated with worse CBM score when restricted to outcomes related to cisplatin exposure, including peripheral sensory neuropathy, hearing loss, tinnitus, vertigo, vestibular disorder, and chronic kidney disease (P = .007).

The average time since chemotherapy at the point of evaluation was about 5 years, and only about 20% of participants had more than 10 years elapse since their last chemotherapy.

Kerns added that her study may underestimate morbidity since most of the participants may not have been at risk long enough to develop some late health outcomes.

Additionally, the cross-sectional design of the study does not allow for an establishment of a causal relationship between CBM score and cisplatin-based chemotherapy exposure.

The researchers concluded that future research should focus on defining validated measures to evaluate long-term CBM among survivors of testicular cancer and eventually develop risk-adapted survivorship care plans.

Kerns SL, Fung C, Williams A, et al. Cumulative burden of morbidity (CBM) among testicular cancer survivors (TCS) in the Platinum study. Presented at: Cancer Survivorship Symposium; January 15-16, 2016; San Francisco, CA. Abstract 106.