She first discussed the TRISST trial, a phase 3 multi-center non-inferiority trial evaluating CT versus MRI and frequency of imaging for surveillance of clinical stage 1 seminoma. This study was motivated by a lack of consistent guidelines around surveillance, and concerns surrounding the significant radiation exposure associated with repeated CT scans for young survivors of this disease. Additionally, with more frequent surveillance, there are often gaps in adherence. Dr. Laguna then summarized the trial, which enrolled 669 men and randomized them 1:1:1:1 to either CT or MRI surveillance with either 3 or 7-scans. Follow-up was conducted for a median of 72 months, and the primary outcome was the 6-year incidence of tumors > 5 cm in size.
The trial anticipated 5.7% of patients to relapse with stage 2C disease or greater and aimed to exclude an increase to greater than 11.4% (double) with fewer scans or switching to MRI. The trial met its primary endpoints of non-inferiority for both MRI imaging and a 3-scan approach, though more patients recurred with the 3-scan approach, half of which could have been detected earlier with more frequent scans.
Dr. Laguna discussed that non-inferiority trials are harder to conduct than superiority trials as the chosen non-inferiority margin must be clinically rigorous. The major caveats she discussed were that the percentage of patients with multiple pathologic risk factors for recurrence was quite low, perhaps limiting interpretation. Also, given that so few patients overall had a recurrence, whether or not the non-inferiority bounds used clinically relevant must be considered. Third, she pointed out that a quarter of patients on the study did not complete the scheduled follow-up, further limiting trial interpretation.
Moving to the SEMS study, Dr. Laguna summarized that the purpose of this trial is to explore RPLND as an efficacious modality to reduce the toxicity from treatment of clinical stage 2A/2B seminoma with radiotherapy or chemotherapy. The primary endpoint was 2-year recurrence-free survival. The trial recruited 55 patients, 41 of which were primary clinical stage 2 patients. Complications occurred in 13% of patients, mostly CLavien-Dindo 1-2, and all patients maintained antegrade ejaculation. At a median follow-up of 2 years, recurrence-free survival was 85% and overall survival was 100%, with the 10 patients recurring managed with either additional surgery (2 patients) or systemic therapy. The authors concluded that RPLND does appear to be a valid therapeutic option in early metastatic seminoma.
Dr. Laguna highlighted multiple strengths of the study. One strength of the study is that for patients with < 2 cm masses, restaging imaging was performed 6-8 weeks later with or without biopsy to unequivocally decide if metastatic disease was present. Dr. Laguna remarked the study design here is excellent, focusing not on the technique but rather the indication for the technique. Other strengths of the study design included clear surgeon requirements and clear surgical approach criteria. However, regarding the conclusion that RPLND is a feasible treatment modality, she urged caution as the study follow-up period is still relatively short and stated that RPLND should not be a standard option currently outside of a clinical trial or institutional study protocol. Longer-term follow-up data from SEMS as well as results from other trials such as PRIMETEST (NCT02797626) will help provide additional data to evaluate the role of surgery in early metastatic pure seminoma.
Presented by: Pilar Laguna, MD, PhD, AMC University Hospital
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021