PRIMETEST II - Clinical Stage II A/B Seminoma Treated With RA-RPLND

Testicular cancer stands as the most prevalent cancer among young men, boasting a highly favorable prognosis characterized by almost unaltered long-term survival even in advanced stages. However, traditional treatments like chemotherapy and radiation are linked to significant long-term toxicity and increased rates of secondary malignancies. Particularly, late toxicities, mainly cardiovascular, substantially diminish overall survival by approximately 6-7 years. To circumvent unnecessary acute and long-term toxicities associated with radiation or chemotherapy, it's crucial to explore alternative therapeutic avenues through personalized, less toxic approaches.

Building upon the hypothesis-generating PRIMETEST I study, PRIMETEST II is a single-arm, non-randomized prospective study. It aims to explore novel and personalized predictive parameters for recurrence following a robot-assisted primary retroperitoneal lymph node dissection (pRA-RPLND) in patients with clinical stage IIA/B seminoma (involving low-volume metastatic disease up to 5 cm). These patients represent a rare subgroup among testicular cancer patients, making a randomized comparison of treatment options impractical due to their low prevalence. The overarching goal is to reduce long-term toxicity in this young cohort of cancer patients and enhance their quality of life through personalized clinical and molecular predictions.

PRIMETEST I has indicated that pRA-RPLND in patients with clinical stage IIA/B seminoma led to a 70% recurrence-free survival at 32 months' follow-up. These findings suggest that pRA-RPLND could serve as an alternative to standard therapies (chemotherapy, radiotherapy) for a highly selective group of patients, effectively preventing excessive toxicity. PRIMETEST I has already identified several potential factors that predict which patients are more likely to benefit from surgical therapy alone.

In the novel prospective setting of PRIMETEST II, the study tests the identified predictive factors for recurrence. Patients exhibiting presumably low-risk features (about 70% of patients) will continue with surgery alone. Those with a presumed higher risk of recurrence will undergo robot-assisted surgery and have the option of receiving adjuvant treatment (one cycle of cisplatin, etoposide, and bleomycin). The primary endpoint is a three-year recurrence-free survival, estimated to exceed 90%. Additional objectives include exploring new predictors of recurrence at both molecular and clinical levels by analyzing serum and tissue samples from the primary tumor and metastases.

This innovative approach anticipates that 70% of patients will avoid long-term toxicity and experience excellent recurrence-free survival rates comparable to standard chemotherapy or radiation therapy.

• Overall survival [Time frame: at least 5 years]
• Time to progression [Time frame: from intervention to progression assessed up to 5 years]
• Complications [Time frame: intra- and perioperative]
• Quality of life [Time frame: baseline and yearly, up to 5 years]
• Mental health [Time frame: baseline and yearly, up to 5 years]
• Rate of retrograde ejaculation [Time frame: postoperative assessment yearly, up to 5 years]
• Validation of microRNA-371 [Time frame: Day before surgery, day 3-5 after surgery and in case of adjuvant therapy 3 days from last drug application]
• Analysis of molecular characteristics [Time frame: after study recruitment completion]