In a Swiss/German phase II trial (SAKK 01/10) reported in The Lancet Oncology, Papachristofilou et al found that a single dose of carboplatin followed by involved-node radiotherapy narrowly missed the target 3-year progression-free survival rate in patients with stage IIA or IIB seminoma. 

As stated by the investigators, “Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy or three to four cycles of cisplatin-based combination chemotherapy. These options result in 3-year progression free survival rates of at least 90%, but bear risks for acute and late toxic effects, including secondary malignancies. We tested a novel approach combining de-escalated chemotherapy with de-escalated involved-node radiotherapy, with the aim of reducing toxicity while preserving efficacy.”

Study Details

The multicenter trial included 116 patients with stage IIA (n = 46) or IIB (n = 70) classic seminoma (at primary diagnosis or at relapse during active surveillance for stage I disease) enrolled between October 2012 and June 2018. They received single-dose carboplatin at area under the curve 7 followed by involved-node radiotherapy at 30 Gy in 15 fractions for stage IIA disease and at 36 Gy in 18 fractions for stage IIB disease. The primary endpoint was 3-year progression-free survival, with a target rate of 95%.  

Progression-Free Survival

After median follow-up of 4.5 years (interquartile range = 3.9–6.0 years), seven patients relapsed (one with stage IIA and six with IIB disease) and one patient (with stage IIA disease) died. The 3-year progression-free survival rate was 93.7% (90% confidence interval [CI] = 88.5%–96.6%), which did not achieve the target rate of 95%. Progression-free survival at 3 years was 95.2% (90% CI = 85.5%–98.5%) in patients with stage IIA disease and 92.6% (90% CI = 85.2%–96.4%) in patients with stage IIB disease.

Seminoma-specific survival was 100% (95% CI = not estimable to not estimable). One patient died from a second primary cancer—cholangiocarcinoma—2.5 years after trial inclusion, resulting in 3-year overall survival of 99.3% (90% CI = 95.3%–99.8%).

Adverse Events

Acute treatment-related adverse events of any grade occurred in 48% of patients. Grade 3 or 4 treatment-related adverse events consisted of neutropenia in 4% of patients, thrombocytopenia in 3%, and vomiting in 1%. Serious adverse events occurred 4% of patients, consisting of transient creatinine increase in one patient and second primary tumors in four. The four second primary tumors observed in the study consisted of stage I seminoma of the contralateral testis in two patients, and clear cell renal cell carcinoma in one and cholangiocarcinoma in another—both of which developed outside of radiation fields. No treatment-related deaths and no late treatment-related adverse events were reported.

The investigators concluded, “Despite the fact that the primary endpoint was not met, we observed favorable 3-year progression-free survival with single-dose carboplatin area under the curve 7 and involved-node radiotherapy, with minimal toxic effects. Our findings might warrant discussion with patients about the SAKK 01/10 regimen as an alternative to standard-of-care treatment, but more research on this strategy is needed.”

Alexandros Papachristofilou, MD, of the Department of Radiation Oncology, University Hospital Basel, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the Swiss State Secretariat for Education and Research and Innovation and Rising Tide Foundation for Clinical Cancer Research. For full disclosures of the study authors, visit thelancet.com.