Background: As cure rates for patients with advanced TGCT improve, there is increasing focus on quality of survival. Increasingly, primary RPLND is being used as an alternative to chemotherapy (and radiotherapy) as primary treatment for selected individuals, due to the development of low morbidity surgical techniques (robot-assisted and extraperitoneal approaches), and recognition of acute and long-term toxicity of chemotherapy and radiotherapy. We hypothesise that primary RPLND compared to chemotherapy and radiotherapy will have less detrimental impact on HRQoL with comparable oncological outcomes. Methods: PRESTIGE is a prospective cohort study among adults with histologically confirmed advanced TGCT planned for primary RPLND, chemotherapy or radiotherapy. Eligible patients may have de novo advanced disease, or relapse within two- (NSGCT) or three-years (seminoma) following orchidectomy, without prior chemotherapy or radiotherapy (including adjuvant), and able to complete HRQoL questionnaires in English. See table for cohort-specific eligibility. Surgical approach (modality, template, adjuvant chemotherapy), chemotherapy regimen and radiotherapy dose will be administered at physician discretion and captured in Australia’s national multi-centre TGCT registry, iTestis, with clinical data in follow-up. Participants will complete HRQoL questionnaires focusing on physical, social, emotional, and functional domains commencing prior to treatment and continuing for 24 months. Questionnaires include EORTC QLQ-C30, EORTC QLQ-TC26, Brief Male Sexual Function Inventory and specific questions focusing on retrograde ejaculation and fertility. Patients undergoing RPLND will also have miR-371 evaluation pre-operatively and serially for 12 months after surgery. The primary outcome is change in EORTC QLQ-C30 global health status over 24 months for participants undergoing primary RPLND. Key secondary outcomes are changes in HRQoL, patterns of recurrence, surgical complications, retrograde ejaculation, and infertility. A sample size of 90 participants (30 for RPLND, 60 for chemotherapy) provides >80% power to detect a mean difference of 28% in global health status at 0.05 significance favouring RPLND. Up to 30 individuals receiving radiotherapy may also be enrolled. The first site was activated 4-Aug-22; 2 of 3 study sites are active and 5 out of a planned 120 (4%) participants have enrolled.