New approaches to testicular cancer treatment

A Story by Dr Alexandros Papachristofilou
University of Basel

Testicular cancers are the most common malignancies in men aged between 18-35 years. Of those, seminoma is the most frequent as it accounts for about half of all testicular cancers. Seminoma is classified according to the involvement and degree of spreading to lymph nodes and to the lung or other organs. Around 10% of all seminoma patients are diagnosed with stage IIA/B disease.

Seminoma stage IIA/B is highly responsive to chemotherapy and radiation therapy and the progression free survival (PFS) at 5 or 6 years with such treatments is between 87-95%. Supra-diaphragmatic lymph nodes are the usual site of tumor recurrence after radiation therapy, while local failure or tumor persistence in paraaortic lymph nodes is predominant after chemotherapy.

Dr. Papachristofilou from the Basel University Hospital speculated that a therapy de-escalation protocol with good efficacy should combine suboptimal carboplatin chemotherapy (1 cycle) with a limited volume of radiation therapy targeting the involved nodes only (30 or 36 Gy for stage IIA or IIB, respectively).

This was a multi-center, single arm trial, in which both stage IIA and IIB patients were included. 13 sites in Switzerland and 10 sites in Germany participated in the trial.
120 patients were enrolled over 6 years, 66 in Switzerland and 54 in Germany.

Therapy compliance, acute side effects, and efficacy of treatment were encouraging. Results regarding the primary endpoint (progression free survival at 3 years) will be available in 2021.

Based on the encouraging preliminary results, the team decided to adapt the therapy regime to test a further lowered radiation dose and a slightly intensified chemotherapy for a subgroup of patients. A single-arm, multicenter, prospective phase II trial with 130 patients is proposed. Since seminoma stage IIA/B is a rare disease it is thought that a randomized trial would not be feasible. The primary endpoint of the trial is progression free survival 3 years after registration.

If the proposed treatment regime is proven successful and safe, patients will be able to undergo less aggressive treatment exposing them to lower risks for long term treatment side-effects, including secondary malignancies.

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