To the Editor:

Oliver et al¹ claim that contralateral tumors in patients with seminoma can be largely prevented by the adjuvant administration of carboplatin. However, this conclusion should be drawn cautiously, given that it relies merely on clinical observations and is hampered by a short follow-up period.

Approximately 40% to 50% of bilateral tumors occur after more than 5 years.² Clearly, clinical follow-up is encumbered by the possibility of missing late events. More valuable information with respect to the possible incidence of second testicular tumors can be obtained by searching for testicular intraepithelial neoplasia (TIN; also called carcinoma in situ testis or intratubular germ cell neoplasia). This lesion is the uniform progenitor of all testicular germ cell tumors, and it is safely detected by testicular biopsy.³ Briefly, if TIN is present in a testis then invasive cancer will develop in practically all cases over time. Conversely, if no TIN is found by biopsy, then malignancy is extremely improbable even in the distant future. Therefore, in studying the presumed protective effect of carboplatin with respect to the occurrence of contralateral cancer, searching for TIN represents a much more sensitive tool than does simple clinical observation.

We recently completed a retrospective multicenter survey of the treatment of TIN that comprised 231 patients with testicular germ cell tumors and biopsy-proven contralateral TIN. The vast majority of this population received radiotherapy of the testis or, alternatively, cisplatin-based multidrug chemotherapy. Notably, a subset of 15 patients with seminoma and contralateral TIN underwent treatment with carboplatin at a dosage of 7 × area under the curve, according to European guidelines.⁴ Strikingly, eight patients showed persistence of TIN on a repeat testicular biopsy, and two other patients developed a second seminoma after 4.5 and 11 years, respectively. Only two patients were found to be TIN-free when the repeat biopsy was performed. The three remaining patients had no repeat biopsy performed and are still under observation; no second tumor has developed in any of the three patients after a median observation time of 50 months.

In comparison, another subset of the study population comprised 11 patients who underwent surveillance with no particular treatment for TIN. Of this group, six patients developed invasive seminoma during follow-up. Thus, the presumed cancer-preventing efficacy of carboplatin was not demonstrated in two thirds of patients, and this result is practically identical to the outcome that could be expected if no treatment were administered.

Our experience is at odds with the observations of Oliver et al.¹ Although we are deeply convinced with respect to the benefits of carboplatin in the adjuvant management of stage I seminoma, we must raise serious doubts regarding the presumed efficacy of this drug in the prevention of contralateral testicular cancer.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.