The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection - A 13-year follow-up analysis of a phase III trial cohort.

BACKGROUND: One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up. METHODS: Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75). RESULTS: With a median follow-up of 13.8 years (0-22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96-100%)/92% (CI 89-99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87-97%)/93% (CI 86-97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01). CONCLUSIONS: With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.

Human chorionic gonadotropin-positive seminoma patients: A registry compiled by the global germ cell tumor collaborative group (G3).

BACKGROUND: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients. METHODS: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment. Statistical analysis, including multivariate regression, was performed to identify risk factors. Primary end-points were overall survival (OS) and recurrence-free survival (RFS). RESULTS: We recruited 1031 hCG-positive patients (stage I: n = 586; stage II + III: n = 427) diagnosed between 1981 and 2018. In metastatic disease, LDH levels ≥3 above upper normal limit (UNL) pre- (n = 109) or post-orchiectomy (n = 73) and patients aged ≥40 years (n = 187) were associated with poor prognosis: 5-year OS rates of 84% (LDH ≥3 UNL pre-orchiectomy) versus 92% (<3 UNL pre-orchiectomy) (hazard ratio [HR]: 3.155, [95% confidence interval {CI}: 1.28-7.75], P = 0.012), 82% (≥3 UNL post-orchiectomy) versus 92% (<3 UNL post-orchiectomy) (HR: 6.877, [95% CI: 1.61-29.34]; P = 0.009) and 86% (≥40 years) versus 91% (<40 years) (HR: 6.870, [95% CI: 1.45-13.37], P = 0.009), respectively. A subset of patients with hCG levels ≥2000 IU/l pre-orchiectomy (n = 17) exhibited a poor prognosis, with 5-year OS rates of 73% (≥2000 IU/l) versus 94% (<2000 IU/l) (HR: 3.936, [95% CI: 1.02-12.61], P = 0.047). CONCLUSIONS: Age and LDH levels are significantly associated with poor prognosis in hCG-positive seminoma patients. A small number of patients, with levels of hCG ≥2000 IU/l, may represent a separate prognostic subgroup associated with impaired survival rates.

Preservation of Ejaculatory Function After Postchemotherapy Retroperitoneal Lymph Node Dissection (PC-RPLND) in Patients With Testicular Cancer: Template vs. Bilateral Resection.

Background: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays a crucial role in treatment of metastatic non-seminomatous germ cell cancer. Objective: To evaluate the functional outcome regarding the preservation of ejaculatory function comparing a bilateral vs. unilateral template resection in PC-RPLND patients. In addition, oncological safety and perioperative complications of the unilateral template resection was compared to the full bilateral one. Design/Setting/Participants: Between 2003 and 2018, 504 RPLNDs have been performed in 434 patients. The database of consecutive patients was queried to identify 171 patients with PC-RPLND after 1st line chemotherapy for a non-seminoma with or without bilateral template resection. Re-Do's, late relapse, salvage patients, and thoraco-abdominal approaches were excluded. Indication for a template resection was a unilateral residual mass mainly <5 cm as published (1). Outcome, Measurement, and Statistical Analysis: Descriptive statistics were used to report preoperative features, postoperative outcomes and patterns of recurrence, on the overall population and after stratification for the type of resection (bilateral vs. unilateral). Kaplan-Meier analyses were used to describe recurrence- and cancer-specific mortality-free survival rates at different time points. Results and Limitations: Overall, 90 and 81 patients underwent unilateral and bilateral radical resection, respectively. Median size of residual mass was 7 cm for bilateral and 4 cm for unilateral template resection. Clinical stage II and III were present in 31 and 69% of patients, respectively. Median follow-up was 14.5 months (IQR 3.3-37.6). The 1- and 2-year recurrence-free survival rates were 91 and 91%, and 77 and 72% for patients treated with unilateral template and bilateral resection, respectively (p = 0.0078). Median time to recurrence was 9.5 and 9 months in template and bilateral resection group, respectively. Adjunctive procedures were performed in 56 patients (33%) and were significantly more frequent in the bilateral resection group (43 vs. 23%, p = 0.006). The overall high-grade complication rate (Clavien-Dindo ≥ III) was 6, 3, and 9% in unilateral template and bilateral resection group, respectively (p = 0.6). The rate of preservation of antegrade ejaculation was significantly higher in the unilateral group. Conclusions: Antegrade ejaculation in patients undergoing unilateral template resection with a residual mass <5 cm can be preserved at a much higher rate. Moreover, this surgical procedure is oncologically safe in terms of mid-term recurrence and CSM-free survival rates. This data undermines the growing evidence of limited PC-RPLND being justifiable in strictly unilateral residual mass <5 cm. This data has to be confirmed with a longer follow-up regarding in-field and retroperitoneal recurrences.