Approach to chemotherapy for high-risk, stage 1, non-seminomatous, germ cell testicular tumors

To offer minimized risk-adapted adjuvant treatment on a nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and thereby reducing the need of later salvage chemotherapy while maintaining a high cure rate. From 1998 to 2005, 745 Norwegian and Swedish patients were included into a prospective, community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) management program. Treatment strategy depended on the presence or absence of vascular tumor invasion (VASC). VASC-positive patients were recommended brief adjuvant chemotherapy (ACT) with bleomycin, etoposide, and cisplatin (BEP), whereas VASC-negative patients could choose between ACT and surveillance. At a median follow-up of 4.7 years, there have been 51 relapses. On surveillance, 41.7% of VASC+ patients relapsed, compared with 13.2% of VASC- patients. After one course of BEP, 3.2% of VASC+ and 1.3% of VASC- patients relapsed. The toxicity of adjuvant BEP was low. Eight patients have died, none died from progressive disease. One course of adjuvant BEP reduces the risk of relapse by approximately 90% in both VASC+ and VASC- CS1 NSGCT, and may be a new option as initial treatment for all CS1 NSGCT. One course of adjuvant BEP for VASC+ CS1 reduces the total burden of chemotherapy compared with surveillance or two courses of BEP. SWENOTECA currently recommends one course of BEP as standard treatment of VASC+ CS1 NSGCT, whereas both surveillance and one course of BEP are options for VASC- CS1 NSGCT.

Background Standard management in the UK for high-risk stage 1 nonseminoma germ cell tumours of the testis (NSGCTT) is two cycles of adjuvant bleomycin, etoposide (360 mg/m2), and cisplatin (BE360P) chemotherapy, or surveillance. Objective To test whether one cycle of BE500P achieves similar recurrence rates to two cycles of BE360P. Design, setting, and participants A total of 246 patients with vascular invasion–positive stage 1 NSGCTT or combined seminoma + NSGCTT were centrally registered in a single-arm prospective study. Intervention One cycle comprising bleomycin 30000 IU on days 1, 8, and 15, etoposide 165 mg/m2 on days 1–3, and cisplatin 50 mg/m2 on days 1–2, plus antibacterial and granulocyte colony stimulating factor prophylaxis. Outcome measurements and statistical analysis The primary endpoint was 2-yr malignant recurrence (MR); the aim was to exclude a rate of ≥5%. Participants had regular imaging and tumour marker (TM) assessment for 5 yr. Results and limitations The median follow-up was 49 mo (interquartile range 37–60). Ten patients with rising TMs at baseline were excluded. Four patients had MR at 6, 7, 13, and 27 mo; all received second-line chemotherapy and surgery and three remained recurrence-free at 5 yr. The 2-yr MR rate was 1.3% (95% confidence interval 0.3–3.7%). Three patients developed nonmalignant recurrences with localised teratoma differentiated, rendered disease-free after surgery. Grade 3–4 febrile neutropenia occurred in 6.8% of participants. Conclusions BE500P is safe and the 2-yr MR rate is consistent with that seen following two BE360P cycles. The 111 study is the largest prospective trial investigating one cycle of adjuvant BE500P in high-risk stage 1 NSGCTT. Adoption of one cycle of BE500P as standard would reduce overall exposure to chemotherapy in this young population. Patient summary Removing the testicle fails to cure many patients with high-risk primary testicular cancer since undetectable cancers are often present elsewhere. A standard additional treatment in Europe is two cycles of chemotherapy to eradicate these. This trial shows one cycle has few adverse effects and comparable outcomes to those seen with two cycles.