Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST)
Johnathan Joffe, Fay Cafferty, Laura Murphy, Gordon Rustin, S.A. Sohaib, Rhian Gabe, Sally Stenning, Elizabeth C James, Dipa Noor, Simona Wade, Francesca Schiavone, S. Swift, Elaine Dunwoodie, Marcia Hall, Anand Sharma, Jeremy Braybrooke, Jonathan Shamash, John Logue, H. Taylor, I. Hennig, Jeff White, Sarah Rudman, Jane Worlding, David Bloomfield, Guy Faust, Hilary Glen, Rachel Jones, Michael J. Seckl, Graham Macdonald, Thiagarajan Sreenivasan, Satish Kumar, Andrew Protheroe, Ramachandran Venkitaraman, Danish Mazhar, Victoria Coyle, Martin Highley, Tom Geldart, Robert Laing, Richard Kaplan, Robert Huddart, on behalf of the TRISST Trial Management Group and Investigators
Abstract
PURPOSE Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI ( v CT) or three scans ( v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (–3.5 to –0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION Surveillance is a safe management approach—advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.