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Contemporary management of early stage testicular seminoma.

ABSTRACT: Therapy for early stage testicular seminoma has changed radically over the past several decades. Given high cure rates and clinical trials supporting less active therapy in most cases, close observation after radical orchiectomy is now considered standard of care for clinical stage (CS) IA/IB seminoma, with either radiation therapy (RT) or chemotherapy salvage options possible. For CS IIA/IIB seminoma characterized by non-bulky retroperitoneal lymph node involvement (?5 cm in greatest dimension), RT or combination chemotherapy are the standard of care. Given high comparable survival rates, preventing treatment-related toxicity and second malignancy, and limiting quality of life deficits associated with intense treatment has gained much greater importance. Clinical trials are currently testing the feasibility of retroperitoneal lymph node dissection (RPLND) for low volume CS IIA/IIB metastatic testicular seminoma to this end. Likewise, one cycle of chemotherapy is being evaluated as an adjuvant approach to reduce recurrence rates in CS I disease with unfavorable risk factors. Moreover, recent genomic and molecular studies have recently identified novel signatures and a potential biomarker for testicular seminoma. In this review, we first summarize the evolution of early stage seminoma management and discuss the effectiveness and drawbacks of contemporary treatment strategies. We further outline future perspectives and potential challenges in management of early stage testicular seminoma.

SUBMITTER: Aydin AM

PROVIDER: S-EPMC6995845 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Contemporary management of early stage testicular seminoma.

Aydin Ahmet Murat AM Zemp Logan L Cheriyan Salim K SK Sexton Wade J WJ Johnstone Peter A S PAS

Translational andrology and urology 20200101 Suppl 1

Therapy for early stage testicular seminoma has changed radically over the past several decades. Given high cure rates and clinical trials supporting less active therapy in most cases, close observation after radical orchiectomy is now considered standard of care for clinical stage (CS) IA/IB seminoma, with either radiation therapy (RT) or chemotherapy salvage options possible. For CS IIA/IIB seminoma characterized by non-bulky retroperitoneal lymph node involvement (≤5 cm in greatest dimension) ...[more]

PMID: 32055484

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Project description:ObjectivesPrimary tumor size (PTS) is the main prognostic factor for relapse in clinical stage (CS) IA testicular seminoma (T1N0M0S0) and the 8th edition of the Tumor-Node-Metastasis staging system now subcategorizes pT1 tumors into pT1a and pT1b based on PTS (<3 cm and ≥3 cm, respectively). We attempted to assess PTS as a prognosticator for overall survival (OS) in CS IA seminoma and to evaluate the comparative effectiveness of active surveillance (AS) versus adjuvant therapy (AT) in patients with large primary tumors (LPT).Methods and materialsIn the National Cancer Database (2004-2014), 2455 (47.7%) and 2685 (52.3%) patients with CS IA seminoma were treated with AS and AT, respectively. AT was defined as the receipt of chemotherapy or radiation within 3 months after orchiectomy. A cut-point analysis was performed to determine the optimal PTS threshold predicting OS at 5 years after orchiectomy. Inverse-probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients with LPT (using the optimal PTS cut-point) treated with AS versus AT.ResultsIn adjusted analysis, pathologic T-stage (pT1a vs. pT1b) did not predict OS and no OS benefit was noted in pT1b patients treated with AT. The optimal PTS cut-point was 4.5 cm. In multivariable analysis, patients with LPT (≥4.5 cm) had an increased risk of overall mortality (HR = 1.87, P = 0.003). Kaplan-Meier curves revealed that OS was superior in patients with LPT treated with AT (IPTW-adjusted log-rank P = 0.029). In IPTW-adjusted Cox regression analysis, AT was associated with an OS benefit in patients with LPT (HR = 0.59, 95%CI: 0.39-0.91, P = 0.017).ConclusionsIn this National Cancer Database analysis, PTS was a predictor of OS in CS IA seminoma. An OS benefit was noted for individuals with LPT (defined as PTS ≥4.5 cm) managed with AT. These findings may warrant refinement of Tumor-Node-Metastasis staging system.

Project description:PurposeSurvival 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.MethodsA 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.ResultsSix 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.ConclusionSurveillance 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.

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Contemporary management of early stage testicular seminoma.

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Contemporary management of early stage testicular seminoma.

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