De-Escalated Combo Treatment for Seminoma Warrants Further Research

By Leah Lawrence - Last Updated: October 31, 2022

Progression-free survival for stage IIA and stage IIB seminoma was improved with the use of single-dose carboplatin and involved-node radiotherapy, but failed to meet the primary endpoint set out in a phase-2 trial of the treatment strategy.

“Standard treatment options for patients with stage IIA or stage IIB seminoma include either para-aortic and pelvic radiotherapy, or 3 to 4 cycles of cisplatin-based combination chemotherapy,” researchers wrote in Lancet Oncology. “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.”

The phase-2 trial was designed to test de-escalated chemotherapy and de-escalated involved node radiotherapy in an attempt to reduce toxicity.

The trial included 116 patients with stage IIA or IIB classic seminoma. The patients were treated with 1 cycle of carboplatin followed by involved-node radiotherapy of 30 Gy in 15 fractions (for stage IIA) or 36 Gy in 18 fractions (for stage IIB). The median age of patients was 40.

After a median of 4.5 years, the 3-year progression-free survival was 93.7%. Out of the patient test group, 7 had disease relapse and 1 patient died. However, the target progression-free survival was 95% at 3 years, thus the trial failed to meet its primary endpoint. Median progression-free survival was not yet reached.

Seminoma-specific survival at the time of the analysis was 100%. The patient death that occurred was due to a second primary cancer diagnosed after the trial began.

“The acute toxicity profile in our trial differs from standard-of-care radiotherapy and cisplatin-based combination chemotherapy, which commonly lead to substantial acute toxic effects in around 50% of patients,” the researchers wrote.

Acute treatment-related adverse events of any grade were observed in 48% of patients. Grade 3 or 4 adverse events included neutropenia (4%), thrombocytopenia (3%), and vomiting (1%). No treatment-related deaths or late treatment-related adverse events were reported. Serious adverse events were seen in 5 patients (4%).

“Sceptics might point to data showing testicular germ cell tumor survivors receiving combined modality treatment are at the highest risk for secondary malignancies compared with those receiving only single-modality treatment,” the researchers wrote. “However, these data concerned patients who received full-dose radiotherapy and full-dose chemotherapy due to disease recurrence after 1 of the 2 modalities.”

Instead, based on these results, the researchers concluded that “de-escalated combined modality treatment warrants further study in this setting.”



Single-Dose Carboplatin Followed by Involved-Node Radiotherapy for Stage IIA and Stage IIB Seminoma (SAKK 01/10): A Single-Arm, Multicentre, Phase 2 Trial