Primary Testicular Neuroendocrine Tumor Coexisting With Seminoma Sharing Germ Cell Origin

A 40-year-old, male, Japanese patient presented with the complaint of painless, right testicular swelling. Tumor markers for testicular cancer were normal. He underwent radical orchiectomy with the clinical diagnosis of stage I seminoma. Pathological examination revealed seminoma and coexisting neuroendocrine tumor (NET). Germ cell neoplasia in situ (GCNIS) was present in the vicinity of seminoma, but there was no continuity between NET and seminoma. Tumor cells of both lesions displayed amplification of 12p and isochromosome 12p on fluorescence in situ hybridization, suggesting that both tumors originated from GCNIS. The present report is the first to describe a case of primary testicular NET coexisting with seminoma in an ipsilateral testis.

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

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.

Clinical utility of the AJCC eighth edition pT1 subclassification and impact on practice patterns in stage I seminoma.

377 Background: The American Joint Committee on Cancer 8th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns has not been studied. Methods: We retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004-2016. Receiver operating curves (ROC) were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among stage I patients. Results: 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under ROC: 0.546). Surveillance has grown as the preferred treatment after orchiectomy – 32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated. Conclusions: The 3 cm cutoff for subclassification of stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized.