Randomized Phase III Trial Comparing Retroperitoneal Lymph Node Dissection With One Course Of Bleomycin And Etoposide Plus Cisplatin Chemotherapy

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 31 Jul 2008 - 0:00 PDT

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UroToday.com - In the June 20, 2008 issue of the Journal of Clinical Oncology, Dr. Peter Albers and colleagues presented the results of a large randomized German trial in men with stage I nonseminomatous germ cell tumors (NSGCT). The treatment options for these patients included active surveillance, retroperitoneal lymphadenectomy (RPLND), or one course of BEP chemotherapy. The hypothesis of the study was that one cycle of BEP chemotherapy is efficacious and results in a lower recurrence rate than RPLND.

Men with stage I histologically confirmed NSCGT were randomized to arm A; one cycle of BEP chemotherapy or arm B; RPLND. The RPLND was an ipsilateral nerve-sparing approach, or at least a modified ipsilateral template dissection was recommended. If metastasis were pathologically confirmed from the surgery, 2 cycles of BEP chemotherapy were given as 21-day cycles. Sample size calculation was based on the previously published cumulative recurrence rates for RPLND (10%) and chemotherapy (3%) to achieve a power of 80%.

Between 1996 and 2005, 382 patients from 61 German centers were randomized to the 2 arms. Arm A and B each enrolled 191 intent to treat patients. The median follow-up was 56 months, and all patients had been observed for at least 15 months. At surgery, 81.5% of patients were found to have pathologic stage I disease. In the intent to treat population, the difference in the 2-year recurrence-free survival rate between those treated with chemotherapy (99.46%) and RPLND (91.87%) was 7.59%. There were 2 and 15 recurrences in the chemotherapy and surgery arms, respectively. Considering outcomes in the according-to-protocol population, there were 15 recurrences, 2 in arm A and 13 in arm B. The 2 chemotherapy recurrences were at 15 and 60 months. The surgery recurrences were all in the first 17 months after orchiectomy. The benefit for recurrence-free survival in the chemo patients was statistically significant (p=0.00330). The hazard ratio to experience a tumor recurrence with surgery as opposed to chemo was 9.74. Among the RPLND recurrences, 5 were retroperitoneal, 2 had synchronous retroperitoneal and mediastinal, and 2 had scrotal relapses. Four men had a solitary pulmonary metastasis. All patients with recurrence had been cured with salvage treatments and there were no cancer-specific deaths.

Grade 3 toxicities were reported in 8.7% of patients with surgery, but most were due to the additional 2 cycles of BEP chemotherapy needed in the pathologic stage II patients. In arm A (receiving one course of BEP), grade 3 toxicity was reported in 37.4%. The study holds promise for the treatment approach using one course of BEP chemotherapy in this setting. While the goal was to test the hypothesis in a community environment, the high numbers of retroperitoneal and scrotal recurrences suggest the quality of the RPLND might be less than at specialized centers.

Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Weissbach L, Loy V, Wittekind C, Hartmann M
J Clin Oncol. 2008 Jun 20;26(18):2966-72
10.1200/JCO.2007.12.0899

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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