ASCO 2020: A 13-Years Follow-up Analysis of a Phase III Trial Cohort: Late Toxicities and Recurrences in Patients with Clinical Stage I Nonseminomatous Germ Cell Tumor After One Cycle of Adjuvant BEP Versus Primary Retroperitoneal Lymph Node Dissection

(UroToday.com) A randomized Phase III trial published in 20081 demonstrated that one cycle of bleomycin, etoposide, and platinum (BEP) therapy was associated with a lower risk of tumor recurrence relative to retroperitoneal lymph node dissection for an unselected population of clinical-stage 1 nonseminomatous germ cell tumors. To examine long term toxicities and confirm long term outcomes for these patients, Andreas Hiester, MD, and colleagues presented 12-year follow-up data of the patients initially enrolled in this clinical trial.

To determine outcomes, registration offices were used to query for current addresses and any deaths. Patients were sent a survey of patient-reported outcomes covering general items as well as specific items related to chemotherapy or surgery. The breakdown of the original trial schema as well as follow-up data are shown below. In total, 45 patients were lost to follow-up, and 23 patients had died, 22 for reasons unrelated to germ cell tumor. In total, 170 patients returned survey data.

clinical stage I nonseminomatous germ cell tumor

In the initial cohort, 15 patients who underwent retroperitoneal lymph node dissection (RPLND) recurred, and two patients who received one cycle of BEP experienced recurrence. One patient in each arm reported disease recurrence in the intervening years, and one patient in the RPLND arm died from their disease. Updated progression-free survival and overall survival were also calculated. This confirmed the recurrence-free survival benefit of one cycle of BEP. No difference in overall survival was detected.

follow up and oncological findings

As shown above, there were numerically more metachronous secondary testis cancer cases in the chemotherapy arm and no difference in second malignancies between the arms.

With regards to long term toxicities, the data are shown below.

patient reported toxicities

Dr. Hiester speculated that the high rate of retrograde ejaculation in the Arm B group, combined with the higher recurrence rate, may reflect an issue with the quality of RPLND.

Overall, in this long-term follow-up data, there were no significant differences in long-term sequelae between groups with the exception of retrograde ejaculation and no changes in the previously reported progression-free survival benefit. Dr. Hiester noted that this study was limited by the use of patient-reported outcomes, the number of patients reached relative to the initial study population, and no formal assessment by a medical examination of the reported toxicities. 

Presented by: Andreas Hiester, MD, Department of Urology, University of Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany

Written by: Alok Tewari, MD, Ph.D., Medical Oncology Fellow at the Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2020 American Society of Clinical Oncology Virtual Annual Meeting (#ASCO20), May 29th-May 31st, 2020

Reference:

  1. Albers, Peter, Roswitha Siener, Susanne Krege, Hans-Uwe Schmelz, Klaus-Peter Dieckmann, Axel Heidenreich, Peter Kwasny et al. "Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group." Journal of Clinical Oncology 26, no. 18 (2008): 2966-2972.