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Risk of Metachronous Contralateral Testicular Cancer According to Platinum-Based Chemotherapy Exposure


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In a Dutch study reported in the Journal of Clinical Oncology, Blok et al found a significant association between an increased number of cycles of platinum-based chemotherapy and a reduced risk of metachronous contralateral testicular cancer. As noted by the investigators, patients with testicular germ cell tumor are at increased risk of developing a contralateral testicular germ cell tumor.

Study Details

The study involved data from a nationwide cohort of 4,755 patients aged < 50 years who were diagnosed with and treated for primary testicular germ cell tumor in the Netherlands between 1989 and 2007. Metachronous contralateral testicular germ cell tumor was defined as any testicular germ cell tumor identified in the contralateral testicle ≥ 2 months after diagnosis of the first testicular germ cell tumor. The cohort included 2,612 patients with seminomatous germ cell tumor and 2,143 with nonseminomatous germ cell tumor.

Standardized incidence ratios were used to compare the incidence of contralateral testicular germ cell tumor incidence with expected incidence of testicular germ cell tumor in the general population. The effect of treatment with platinum-based chemotherapy on contralateral testicular germ cell tumor risk was assessed via multivariable Cox proportional hazards regression models.

“Approximately 1 in every 30 survivors of testicular germ cell tumor will develop a contralateral testicular germ cell tumor, with contralateral incidence increasing up to 20 years after a primary testicular germ cell tumor. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with contralateral testicular germ cell tumor risk.”
— Blok et al

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Key Findings

Metachronous contralateral testicular germ cell tumor was diagnosed in 136 patients (standardized incidence ratio = 14.6, 95% confidence interval [CI] =12.2–17.2). The cumulative incidence increased to 3.4% at 20 years of follow-up, including cumulative incidence of 4.0% after seminomatous germ cell tumor and 2.6% after nonseminomatous germ cell tumor.

The median interval between primary testicular germ cell tumor and metachronous contralateral testicular germ cell tumor was 6.1 years, with no difference between patents with seminomatous germ cell tumor vs nonseminomatous germ cell tumor (P = .090).

The 20-year cumulative incidence was 1.7% in patients who had been treated with platinum-based chemotherapy and 4.4% in patients without platinum exposure (median intervals of 4.9 vs 7.5 years, P = .23).

On multivariate analysis, risk of a contralateral testicular germ cell tumor decreased with every additional cycle of platinum-based chemotherapy (hazard ratio [HR] per cycle = 0.74, 95% CI = 0.64–0.85). The hazard ratio for patients receiving four cycles of platinum-based chemotherapy vs those not receiving platinum-based chemotherapy was 0.18 (95% CI = 0.08–0.43).

Additional significant factors on meta-analysis consisted of reduced risk with increasing age (HR = 0.93, 95% CI = 0.90–0.96) and reduced risk after primary nonseminomatous germ cell tumor vs seminomatous germ cell tumor (HR = 0.58, 95% CI = 0.35–0.96).  

The investigators concluded, “Approximately 1 in every 30 survivors of testicular germ cell tumor will develop a contralateral testicular germ cell tumor, with contralateral incidence increasing up to 20 years after a primary testicular germ cell tumor. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with contralateral testicular germ cell tumor risk.”

Michael Schaapveld, PhD, of the Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by KWF Kankerbestrijding and Dutch Uro-Oncology Studygroup. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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