Increased chemo reduces risk of subsequent contralateral testicular tumor

The more cycles of platinum-based chemotherapy a patient with a testicular germ cell tumor (TGCT) receives, the lower their risk is of developing a metachronous contralateral TGCT (CTGCT), according to findings from a Dutch study published in the Journal of Clinical Oncology.¹

Patients with TGCT face an increased risk of developing a CTGCT. In the study population, patients with primary TGCT had a nearly 15 times higher risk of developing a CTGCT compared with the risk in the general population (standardized incidence ratio, 14.6). Further, among patients with TGCT, the cumulative incidence of CTGCT increased up to 20 years after initial diagnosis, with about 1 in every 30 TGCT survivors developing a contralateral tumor.

Analyzing the impact of prior chemotherapy on patient outcomes, the researchers identified a dose-dependent inverse association with CTGCT risk, whereby the risk decreased with each additional cycle of platinum-based treatment a patient received for their primary TGCT (HR_{per cycle}, 0.74).

“The more chemotherapy cycles a patient has received, the lower their risk of developing CTGCT. Our findings are useful to inform patients of their specific risk of developing CTGCT. Patients should be made aware that this risk is increased for up to 20 years after diagnosis of the first TGCT,” first study author Joost M. Blok, MD, Department of Oncological Urology, University Medical Center Utrecht, Utrecht, the Netherlands, and coauthors wrote.

Prior research has shown that the incidence of CTGCT in survivors of TGCT is approximately 12 to 18 times higher than rates in the general population. The risk is highest within the first 2 decades following the initial TGCT diagnosis, with a cumulative incidence at 20 years of between 2% and 5%, according to the researchers.

The Dutch investigators examined data from 4755 survivors of TGCT identified through the population-based Netherlands Cancer Registry and hospital tumor registries. Patients had received treatment at 11 Dutch hospitals between 1989 and 2007. Among these patients, 136 developed metachronous CTGCT.

Of these 136 patients, 45 had nonseminomatous germ cell tumor (NSGCT) histology and 91 had seminomatous germ cell tumor (SGCT) histology. The median age at diagnosis was 29 years (interquartile range [IQR], 33-40). The primary TGCT stages were I (83.8%), II (9.6%), and III (6.6%). Twenty-two (16.2%) patients had received platinum-based chemotherapy. Overall, 2 patients had 1-2 cycles, 11 patients had 3 cycles, 6 patients had 4 cycles, and 3 patients had more than 4 cycles.

The median time between initial TGCT and diagnosis of CTGCT was 6.1 years (IQR, 3.6-9.4). Overall, 41.2% of patients were diagnosed with CTGCT 5 years after initial TGCT, 38.2% were diagnosed at 5 to 9 years post-TGCT, 15.4% were diagnosed at 10 to 14 years after, and 5.2% were diagnosed at 15 to 20 years after. Beyond 20 years’ follow-up, there were no CTGCTs diagnosed.

The 10-year cumulative incidence of CTGCT was 2.4%, and the 20-year incidence was 3.4%. CTGCT risk was lower in patients with NSGCTs (HR, 0.58). The 20-year incidence rates among the primary SGCT and primary NSGCT subgroups was 4% and 2.6%, respectively. CTGCT risk also decreased with age (HR, 0.93). Thus, the highest 20-year cumulative incidence was in patients with primary SGCT diagnosed prior to age 25, compared with a 20-year incidence of 1% in patients with primary NSGCT diagnosed at age 35 or older.

In their conclusion the authors wrote, “Our findings are useful to inform patients of their specific risk of developing CTGCT. Patients should be made aware that this risk is increased for up to 20 years after diagnosis of the first TGCT.”

Reference

1. Blok JM, Groot HJ, Huele EH, et al. Dose-dependent effect of platinum-based chemotherapy on the risk of metachronous contralateral testicular cancer [published online October 29, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.02352