Therapy de-escalation for testicular cancer (THERATEST): A multi-centre observational cohort feasibility study of de-escalation therapies for good prognosis stage II germ cell tumours.

Background: Standard of care (SOC) treatments for International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis stage II germ cell tumours (GCT) involve primary orchidectomy followed by combination chemotherapy for both seminoma and non-seminomatous germ cell tumours (NSGCT). Alternatively, external beam radiotherapy may be used for seminoma and retroperitoneal lymph node dissection (RPLND) for NSGCT. While these treatments achieve high cure rates, they are associated with significant toxicities. De-escalation strategies including three cycles of Carboplatin AUC10 or robotic RPLND with or without adjuvant chemotherapy have demonstrated potential to reduce treatment-related toxicity in stage II seminoma while preserving oncological efficacy. However, these approaches are not widely adopted due to limited prospective comparative trials. Study Design: The THERATEST trial is a prospective multicentre observational feasibility study evaluating participants receiving SOC treatments for good prognosis stage II seminoma and NSGCT or de-escalated treatments for stage II seminoma. Endpoints: The primary endpoints are to assess feasibility of recruitment and retention. Secondary endpoints include assessing health-related quality of life (HRQOL), sexual function and satisfaction, progression-free survival (PFS), overall survival (OS) and safety and treatment-related complications. Patients and Methods: Thirty participants with good prognosis stage II seminoma or NSGCTs will be recruited over 18 months into two cohorts: de-escalation arm and SOC arm. The de-escalation cohort will receive either Carboplatin AUC10 or robotic RPLND with or without adjuvant therapy depending on institutional SOC. Participants who decline or are ineligible for de-escalation will receive SOC treatment: combination chemotherapy or radiotherapy for seminoma and combination chemotherapy for NSGCT. All participants will be followed for two years post-treatment or until withdrawal. Data collection includes recruitment and retention rates, disease status, surgical outcomes, adverse events and patient-reported outcomes using validated questionnaire: EORTC QLQ-TC26, EORTC QLQ-C30, Brief Male Sexual Function Inventory (BMSFI) and additional enquiries on anejaculation. Coordinating Centre: THERATEST Trial Coordinator, Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, Old Anatomy Building, Charterhouse Square, London, EC1M 6BQ|T: 0207882 8497|E: bci-theratest@qmul.ac.uk. Trial registration number: ISRCTN61007118.