Michael Cullen a , † , ‡ , Robert Huddart b , c , † , * , Johnathan Joffe d , Deborah Gardiner e , Lauren Maynard e , Paul Hutton a , Danish Mazhar f , Jonathan Shamash g , Matthew Wheater h , Jeff White i , Aicha Goubar e , Nuria Porta e , Stephanie Witts e , Rebecca Lewis e , Emma Hall e , on behalf of the 111 Trial Management Group
1 March 2020
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/m 2), and cisplatin (BE 360P) chemotherapy, or surveillance.
To test whether one cycle of BE 500P achieves similar recurrence rates to two cycles of BE 360P.
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.
One cycle comprising bleomycin 30000 IU on days 1, 8, and 15, etoposide 165 mg/m 2 on days 1–3, and cisplatin 50 mg/m 2 on days 1–2, plus antibacterial and granulocyte colony stimulating factor prophylaxis.
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.
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.
BE 500P is safe and the 2-yr MR rate is consistent with that seen following two BE 360P cycles. The 111 study is the largest prospective trial investigating one cycle of adjuvant BE 500P in high-risk stage 1 NSGCTT. Adoption of one cycle of BE 500P as standard would reduce overall exposure to chemotherapy in this young population.
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.
The 111 trial aimed to exclude a 2-yr recurrence rate of >5% with adjuvant one cycle of bleomycin, etoposide (500 mg/m2), and cisplatin (BE500Px1) in stage 1, high-risk nonseminomatous germ cell testis tumours. This was achieved, with 1.3% malignant recurrences among 236 cases. BE500Px1 should replace BE360Px2 as standard care for such patients.