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Although it has been thought that platinum-based chemotherapy is associated with a lower risk for developing a contralateral tumor in patients with testicular cancer, a new population-based cohort study provided stronger evidence of the link.

"Whether such a relationship exists is clinically relevant, as an increasing number of patients with TGCT [testicular germ cell tumor] may receive lower doses of platinum-based chemotherapy now that adjuvant therapy with one or two cycles of chemotherapy in high-risk stage I disease is gaining popularity," wrote Joost Blok, MD, of Utrecht University in The Netherlands, and colleagues, in the study in the .

Blok's group analyzed the medical records of 4,755 patients diagnosed with primary testicular germ cell tumor in the Netherlands from 1989 to 2007. The results showed that the cumulative incidence of contralateral tumor increased up to 20 years after the primary diagnosis, reaching 3.4% at 20 years of follow-up, which was nearly 15 times higher than the expected incidence of testicular cancer in the general population.

Cox proportional hazards regression analysis showed that the risk decreased with age, was lower after nonseminomatous germ cell tumor, and decreased with every additional cycle of platinum-based chemotherapy (HR 0.74 per cycle, 95% CI 0.64-0.85).

"The more chemotherapy cycles a patient has received, the lower his risk of developing CTGCT [contralateral TGCT]," the researchers said. "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."

In the following interview, Blok elaborated on the results.

Previous studies of this issue have yielded conflicting results. How is your study different and what does it add?

Blok: We had very detailed information on all treatment received before the diagnosis of contralateral testicular cancer. This is different from previous studies, which had information only on the initial treatment. So if a patient had a relapse after a couple of years and was treated with chemotherapy, this would be missed.

Also, because we had information on the number of chemotherapy cycles, we were able to analyze the association between contralateral tumor and the number of chemotherapy cycles. Earlier studies analyzed treatment with chemotherapy as a dichotomous variable.

In your opinion, should the findings of your study influence the treatment choice for primary testicular cancer, and if so how?

Blok: The absolute risk of contralateral testicular cancer is low, so our findings should not influence the treatment of choice for primary testicular cancer. Treating high-risk Stage I disease with adjuvant chemotherapy -- e.g., one cycle of BEP [bleomycin, etoposide and platinum] -- is gaining popularity. It could be that this leads to a lower incidence of contralateral testicular cancer, but more studies are necessary to confirm this.

Additional cycles of chemotherapy might lower contralateral tumor risk but could also result in increased toxicity. Do you have any advice for discussing this risk-benefit trade off with patients?

Blok: Patients should be aware that they have an increased risk of developing contralateral testicular cancer and that this can occur for at least 20 years after their initial diagnosis. The absolute risk is low, but patients should understand that they are still at risk after their final follow-up visit with their physician.

What did your study suggest about the duration of follow-up surveillance for contralateral tumors in patients treated for testicular cancer?

Blok: The low risk of contralateral tumor does not, in my opinion, warrant an extension of the follow-up of primary testicular cancer. But patients need to be aware that they might develop testicular cancer for a second time.

Do you plan any additional research on this topic?

Blok: No, we currently have no plans for additional research on contralateral testicular cancer.

Read the study here and expert commentary about the clinical implications here.