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Chemotherapy Administered for the First Diagnosed Testicular Cancer Reduces the Risk of Metachronous Contralateral Testicular Cancer Occurrence

Patients aged less than 30 years upon diagnosis of testicular cancer and those treated with surgery only are at higher risk of developing a metachronous contralateral (second) germ cell testicular cancer, according to a recent article published in the Journal of Clinical Oncology authored by Ragnhild Hellesnes of the Department of Oncology, University Hospital of North Norway and the University of Tromso, Norway and colleagues.

The authors stated that the diagnosis of testicular cancer over a 15 to 20-year time span is associated with a long-term cumulative incidence of contralateral testicular cancer of 1.9 to 3.9%. They noted that it is currently thought that patients treated with cisplatin-based chemotherapy in the management of their testicular cancer have a lower incidence of contralateral germ cell testicular cancer, although data, including treatment details, supporting this hypothesis are lacking.

Therefore, they conducted this population-based cohort study in which 5,620 men diagnosed with testicular cancer between 1980 and 2009 were identified in the cancer registry of Norway. Their treatment information was retrieved from medical records, and the cumulative incidences of a second testicular cancer were estimated. This cohort was categorised according to treatment: 1,417 (25%) patients received surgery only (including surveillance), 2,450 (44%) had chemotherapy, 1,543 (27%) had chemotherapy plus radiotherapy, and 210 patients (3.7%) received radiotherapy only.

Treatment intensity influenced the risk of a second diagnosis of testicular cancer

With median follow-up of 18.0 (interquartile range [IQR] 12.0-25.5) years, 218 men in this cohort were diagnosed with a contralateral testicular cancer after a median of 6.2 years (IQR 3.3–10.6 years), which corresponded to a 20-year cumulative incidence of 4.0% (95% confidence interval [CI] 3.5-4.6).

This incidence was found to be lowered following chemotherapy to 3.2% (95% CI 2.5-4.0), whereas the incidence in patients receiving surgical treatment only was higher at 5.4% (95% CI 4.2-6.8).

The hazard ratio (HR) for a second testicular cancer diagnosis after platinum chemotherapy was 0.55 (95% CI 0.40 – 0.76), which decreased with an increasing number of cycles of platinum chemotherapy. With each additional chemotherapy cycle administered, the risk of a second testicular cancer was decreased significantly: after three cycles (HR 0.53), four (HR 0.41), and more than four cycles (HR 0.21).

The total standardised incidence ratio was 13.1 (95% CI 11.5-15.0), which translated to a risk of a second testicular cancer that was 13-fold higher compared with the risk of developing this cancer in the general male population.

Patients’ age at the first diagnosis also impacted the risk

The incidence of contralateral testicular cancer was 6% (95% CI 5.0-7.1) in patients diagnosed with their first testicular cancer prior to age 30 as compared 2.8% (95% CI 2.3-3.4) in those diagnosed with their first tumour after aged 30.

Conclusions

In summary, the authors stated that these findings provided important data on the incidence of second contralateral testicular cancers using a large population database of men in Norway. They found that secondary cancers were more common if the first diagnosis was made at age <30 years, and less common if patients received platinum chemotherapy as part of the management of their first diagnosis.

The authors wrote that, to the best of their knowledge, their study established for the first time, that the risk of a metachronous contralateral testicular cancer decreased with each additional cycle of chemotherapy, with risk being significantly reduced after more than two cycles.

The investigators suggested that patients with metastatic unilateral testicular cancer may appreciate information on the significant risk reduction of second testicular cancer after chemotherapy. They underscored the importance of patients conducting regular lifelong self-examination.

This study was sponsored by grants from Helse Nord RHF.

Reference

Hellesnes R, Myklebust TA, Bremnes RM, et al. Metachronous Contralateral Testicular Cancer in the Cisplatin Era: A Population-Based Cohort Study. Journal of Clinical Oncology; Published online 23 December 2020. DOI: https://doi.org/10.1200/JCO.20.02713

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