Imaging modality and frequency in surveillance of stage I seminoma testicular cancer: Results from a randomized, phase III, factorial trial (TRISST).

Abstract

374 Background: Survival after orchiectomy in stage I seminoma is almost 100%. CT surveillance is an international standard of care, and avoids adjuvant therapy. In this young population, who are unlikely to die from testicular cancer, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST, NCT00589537), assessed whether CTs can safely be reduced, or replaced with MRI, without an unacceptable increase in advanced relapses. Methods: TRISST is a phase III, multicenter, non-inferiority, factorial trial. Eligible men had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Randomization was to: 7 CTs (6, 12, 18, 24, 36, 48, 60 months (m) after randomization); 7 MRIs (same schedule); 3 CTs (6, 18, 36m); or 3 MRIs (same schedule). Follow-up was for 6 years. The primary outcome is 6-year incidence of RMH stage ≥IIC relapse, aiming to exclude an increase ≥5.7% (from 5.7% to 11.4%) with MRI (vs CT) or 3 scans (vs 7); target n=660, all contributing to both comparisons. Secondary outcomes include relapse ≥3cm, disease-free and overall survival (DFS, OS). Results: 669 men enrolled from 35 UK centers (2008-2014); mean tumor size 2.9cm, 358 (54%) were low risk (≤4cm, no rete testis invasion). Median follow-up was 72m. 82 (12%) patients relapsed. Incidence of stage ≥IIC relapse was low in all groups (n=10). More events occurred with 3 scans vs 7, though non-inferior based on design criteria: 9 (2.8%) vs 1 (0.3%), 2.5% increase, 90% CI 1.0% to 4.1% (intent-to-treat, ITT). 4/9 in 3-scan arms could potentially have been detected earlier with the 7-scan schedule. Fewer events occurred with MRI vs CT: 2 (0.6%) vs 8 (2.5%), 1.9% decrease, 90% CI -3.5% to -0.3% (ITT). Per protocol results were similar. Incidence of relapse ≥3cm was 3.7%; non-inferiority was shown for both comparisons. In all groups, most relapses were detected at scheduled imaging; very few occurred beyond 3 years (5 in 558 at risk, <1%). Relapse treatment outcomes were good (81% complete response) with no tumor-related deaths. 5-year DFS and OS were 87% and 99%, similar across groups. Conclusions:Surveillance is a safe management approach in stage I seminoma – advanced relapse is rare, salvage treatment successful, and long-term outcomes excellent, regardless of imaging frequency or modality. Relapse beyond 3 years is rare and imaging may be unnecessary. MRI is non-inferior to CT, avoids irradiation and should be recommended. Clinical trial information: NCT00589537.

Utilization of imaging for active surveillance in testicular cancer: Is real-world practice concordant with guidelines?

“…13 New data from the TRISST trial also shows non-inferiority of 3 scans during surveillance (at months 6,18 and 36) compared with 7 scans (at months 6,12,18,24,36,48,60) among patients with stage I seminoma and suggests imaging maybe unnecessary beyond 3 years. 14 Despite the detection of under-use and over-use of imaging in our study, our previous study using the same cohort of patients as this study revealed a 5 year survival rate of 97% and cancer specific survival of 98% that is consistent with global data. 3 However, our data do not support purposeful delivery of care that is not consistent with guidelines.…”

Contemporary options and future perspectives: three examples highlighting the challenges in testicular cancer imaging

“…For the assessment of retroperitoneal lymph nodes, abdominal MRI in comparison to abdominal CT yields similar results with a sensitivity between 78% and 96% [ 35 ]. The recently published TRISST study, a phase III non-inferiority trial compared abdominal MRI with abdominal CT for detection of early recurrence in patients with clinical stage I seminoma [ 36 ]. The study consisted of two study comparisons: 3 MRI scans vs. 3 CT scans as well as 7 MRI scans vs. 7 CT scans.…”

Safety of Minimizing Intensity of Follow-up on Active Surveillance for Clinical Stage I Testicular Germ Cell Tumors

“…Recently, the Medical Research Council completed the Trial of Imaging and Surveillance in Seminoma Testis (TRISST-MRC TE24) study. This trial randomized 669 CSI seminoma patients to either CT or magnetic resonance imaging (MRI) and to either three or seven scans over a 5-yr period [25] . Early results presented in abstract form only suggest that MRI imaging was noninferior to CT scans and a three-scan schedule was noninferior to a seven-scan schedule.…”