Following a radical orchiectomy, current UK practice for newly diagnosed, high-risk, stage 1 nonseminomatous or combined germ cell tumours of the testis (NSCGCTT) is either two cycles of adjuvant chemotherapy with bleomycin, etoposide, cisplatin (BE360Px2) or surveillance with BE500Px3 on recurrence. This study looked at whether a single cycle of adjuvant chemotherapy would give similar recurrence rates as two cycles of adjuvant chemotherapy. All participants were given one cycle of BE500Px1 chemotherapy over a three-week period. Within the first four weeks, they received a full clinical assessment. They were then followed up at regular intervals for five years with regular CT scans of the chest, abdomen and pelvis as well as tumour markers and chest X-rays. The primary endpoint was malignant recurrence at two years. Other secondary outcomes measures were also included in this study. This study has demonstrated the efficacy of adjuvant BE500Px1 for high-risk (VI+) stage 1 (NSCGCTT) with malignant recurrence rates of just 1.3% and 1.8% at two and four years, which were almost identifcal to having two cycles of adjuvant chemotherapy, as shown in other European studies. Limitations to this study include the concerns with late toxicity but the authors argue there is a clear relationship with cycle number (therefore cumulative doses) and delayed toxicity. Fertility indices have yet to be reported. The other obvious limitation is that this is a single arm study and therefore no direct comparison can be drawn with two cycles of chemotherapy. The sample size is small (about 20% of what is needed) although when combined with the other two similar studies we have data on 937 men who have received one cycle of adjuvant BEP. The findings here are promising and if the same results can be achieved with one cycle then this is the way forward avoiding adverse events associated with further cycles. This study has high external validation in a real-world-setting and adds to the growing body of evidence to support the efficacy of one cycle of adjuvant BEP which may become the standard of care. In these studies a criterion for high risk for relapse was lymphovascular invasion (LVI); the current study shows that a single course of BEP reduces the risk of relapse by 90-95% regardless of LVI status, and may spare close to 50% of men the burden of salvage therapy. The editorial comment on this paper has drawn attention to the use of the terms ‘malignant recurrence’ and ‘benign recurrence’ with the latter being those marker-negative relapse with teratoma only after RPLND; this is somewhat unusual and has been cautioned against due to the potential for malignant transformation.
