Chemotherapy better than lymph node surgery for nonseminomatous testicular germ cells

28 May 2008

Chemotherapy proves more effective in preventing recurrence of nonseminomatous testicular germ cell tumours than lymph node surgery

Chemotherapy is more effective as adjuvant treatment in preventing recurrence of testicular germ cell tumours than surgical removal of lymph nodes, according to the largest randomised trial yet. Testicular germ cell tumours are the commonest solid cancers in young men. Around three-quarters of men with these tumours are diagnosed at an early stage (clinical stage I). Just less than half of these have nonseminomatous germ cell tumours of the testis - cancers that start from cells used to make sperm.

Initial treatment of these cancers involves surgery to remove the affected testicle - orchidectomy. However, nearly one in three men (30%) relapse during follow-up. Further surgery to remove lymph nodes in the lower abdomen close to the testis (retroperitoneal lymph node dissection) reduces the risk of relapse by 8%. Chemotherapy with two cycles of the anticancer drugs bleomycin, etoposide and cisplatin in combination reduces relapse by 2%.
The probability of surviving cancer in the absence of other causes of death is close to 99% using surveillance, adjuvant chemotherapy or retroperitoneal lymph node dissection, so it might seem logical to use them as adjuvant treatment strategies in all men with stage I nonseminomatous testicular germ cell tumours. The problem with this is that chemotherapy and lymph node surgery are both associated with long-term side-effects.

Retroperitoneal lymph node dissection is associated with complications during and after surgery, and causes loss of ante-grade ejaculation - the normal movement of sperm out through the penis. Chemotherapy causes acute toxicity, including hair loss and low white blood cell count, and can cause long-term side-effects such as secondary cancers, cardiovascular problems and depression. As two in three men are not at risk of relapse, they would be unnecessarily exposed to these side-effects if adjuvant treatments are used in everyone.

Cancer researchers from the German Testicular Cancer Study Group decided to see whether one cycle of chemotherapy could reduce the risk of recurrence in men with stage I nonseminomatous testicular germ cell tumours as effectively as lymph node surgery.Between 1996 and 2005, they randomly allocated 382 men with stage I nonseminomatous testicular germ cell tumours to either retroperitoneal lymph node dissection or one cycle of chemotherapy with bleomycin, etoposide and cisplatin after orchidectomy.

Results showed that tumour recurrence was nearly eight times higher in the men treated with adjuvant surgery (8%) patients had recurrences - compared with those given chemotherapy (1%) after a median follow-up of nearly five years (hazard ratio 7.937, 95% confidence interval 1.808 to 34.48, p=0.0011).
The two-year recurrence-free survival rate was 99.46% with chemotherapy and 91.87% with surgery.

"To our knowledge, this is the largest randomised trial in patients with nonseminomatous germ cell tumours of the testis comparing retroperitoneal lymph node dissection with one adjuvant course of chemotherapy. Results showed a significant reduction in recurrences in favour of chemotherapy," commented the researchers, led by Peter Albers, from the Department of Urology, Klinikum Kassel, Kassel, Germany.

They concluded: "If adjuvant proactive treatment without risk factor analysis is the desired option, one course of bleomycin, etoposide and cisplatin is a possible treatment option compared with lymph node dissection." They further suggested that this chemotherapy regimen should also be tested in patients at high risk for recurrence.