Noel Clarke, MBBS, FRCS, ChM

Formal discussant of the 111 trial, Prof. Noel Clarke, MBBS, FRCS, ChM, The Christie Hospital, Manchester, UK, had some concerns, but overall felt that the study could be practice-changing. “In this paper, single-cycle treatment is safe and effective, and two cycles of adjuvant BEP (bleomycin, etoposide, and cisplatin) are unnecessary. These findings may alter the views of the international community,” he said.

“Patients with lymphovascular disease will have treatment failure early, and 40% will develop disease in the retroperitoneal area and elsewhere. Originally they were treated with two cycles of BEP, but this can be toxic in the short and long term. Experts are mixed in their approach, with regard to surveillance and one or two cycles of BEP,” Prof. Clarke explained.

The study had excellent results, with a malignant recurrence-free survival of 99%, and a small number of true active recurrences at the 2-year time point, he continued.

Further Considerations

“Why not give this regimen to all patients with stage I nonseminomatous or combined germ cell tumors of the testis? It does have toxicity. Neutropenia occurred even with growth factor support, and significant loss of hearing was seen. Bear in mind that 60% of these patients would not have had disease progression in any case,” Prof. Clarke noted.

“Looking at surveillance—taking the opposite view—the overall expected relapse rate is 30.6% for stage I nonseminomatous or combined germ cell tumors of the testis. Patients with lymphovascular invasion and embryonal carcinoma are at genuinely high risk and should have intervention,” he stated. “Surveillance is generally safe in this cancer, and the cure rate is high. In the future, high-risk factors should be considered to enable selection of patients for risk-adapted treatment.

“But there is a sting in the tail if surveillance is used,” he continued. “Patients who [have disease progression on surveillance] and go on to get salvage therapy with three to four cycles of BEP require postchemotherapy surgery more commonly. In a recently published large-scale population-based study from Denmark, one in four men treated with active surveillance who [had progression] and needed chemotherapy also required a retroperitoneal lymph node dissection. This is the price to pay if you have treatment failure and require three cycles of BEP.” ■

Disclosure: Prof. Clarke reported no potential conflicts of interest.