Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST)

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.

Oncological Follow-up Strategies for Testicular Germ Cell Tumours: A Narrative Review

“…For nearly 90% of relapses, recurrence is observed in the retroperitoneum, for which an abdominal CT scan is the most common modality for detection [2] , [5] , [10] . By contrast, recurrence detected via clinical examination, chest X-ray, or STMs (bHCG, AFP, or LDH) alone is observed in 0–5%, 0%, and 5–10% (bHCG 3–11%, AFP 0–2%) of cases, respectively [2] , [7] , [9] , [11] . Although seminomatous GCT by definition does not produce AFP, this marker is assessed during follow-up as a few patients initially diagnosed with seminoma may experience recurrence with an AFP-producing nonseminomatous GCT.…”

“…The aforementioned site-specific and modality-specific recurrence patterns have resulted in recommended follow-up that includes abdominal CT scans every 6 mo in the first 2–3 yr and every 12 mo in years 4 and 5 ( Table 1 ). Those recommendations are likely to change after the recent publication of data from the TRrial of Imaging and Surveillance in Seminoma Testis (TRISST) [11] . This randomised trial demonstrated the noninferiority of MRI compared to CT during follow-up for patients with stage I seminoma and the noninferiority of three versus seven radiological assessments using cross-sectional imaging.…”

“…Although there was an absolute increase of 2.5% in events with three versus seven scans, the 5-yr survival was excellent at 99% in all arms. In summary, the TRISST data will increase the use of MRI and help to reduce the frequency of imaging [11] . Imaging of the chest is not recommended in any guideline or institutional follow-up protocol.…”

Canadian Urological Association consensus guideline: Management of testicular germ cell cancer

“…Further interpretation and discussion of these results will be required to recommend a more optimal surveillance schedule to minimize radiation exposure without compromising outcomes. 31…”

Improving outcomes in germ cell cancers using miRNA

“…In addition, MRI was non-inferior to CT, offering an attractive alternative approach and avoiding cumulative radiation exposure in wellresourced settings. 44 While imaging (bio)markers add useful clinical information for some men with TGCT, there remain a number of clinical scenarios where better biomarkers could revolutionize and personalize the care of these men. miRNAs are a promising biomarker in this space.…”