The recent Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection (RPLND) as a first-line treatment for patients with pure seminoma and isolated 1-3–cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either multiagent cisplatin containing chemotherapy or radiation (XRT). While these treatments are highly effective with cure rates over 95%, long-term toxicities such as infertility, cardiovascular disease, bone marrow suppression, peripheral neuropathy, restrictive lung disease, and secondary malignancy can significantly impact quality of life. Up-front surgery, despite slightly higher recurrence rates, may result in avoidance of these long-term toxicities without compromising cancer-specific survival. Understanding the cost utility tradeoffs of these treatments, including management of the downstream effects of toxicities, is needed to help guide shared decision-making. Herein, we evaluated the relative cost-effectiveness of RPLND, XRT, and chemotherapy (3 cycles of cisplatin, etoposide, bleomycin) for management of stage IIA seminoma using a microsimulation model based on SEMS trial results.

Probabilities of progression for RPLND were obtained from published SEMS trial data. All other probability and utility values were obtained from the literature. Recurrences were treated with 3 cycles of bleomycin in chemotherapy-naïve patients, 4 cycles of paclitaxel, ifosfamide, and cisplatin in patients who previously received chemotherapy and recurred within 2 years, and RPLND when recurrences were greater than 2 years after initial treatment. Analyses were performed with a 3-month time cycle for a lifetime horizon. Primary outcomes included costs from a commercial insurer’s perspective, effectiveness (quality adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100,000/QALY was used. One-way and probabilistic sensitivity analyses were performed with 100,000 iterations to evaluate model robustness.

At a lifetime horizon, the mean costs per patient for RPLND, XRT, and chemotherapy were $41,291, $75,650, and $85,380, respectively. The mean QALYs per person were 41.65, 41.62, and 39.60 for RPLND, XRT, and chemotherapy, respectively. RPLND was found to be the most cost-effective approach due to high costs and the accrued disutility of chronic toxicities associated with both XRT (ICER: −$107,296/QALY) and chemotherapy (ICER: −$26,941/QALY). On 1-way sensitivity analyses (see Figure), XRT was more cost-effective than RPLND if the probability of infertility after RPLND was 35% or higher, the utility of infertility was less than 0.46, the probability of progression after RPLND was greater than 48% at 2 years, or the probability of cardiovascular toxicity after XRT was less than or equal to 7%. The proportion of iterations in which RPLND was the most cost-effective treatment option increased over time and RPLND remained the most cost-effective option at a 15-year time horizon and beyond.

Figure: One-way sensitivity analyses. CV indicates cardiovascular; QALY, quality-adjusted life year; RPLND, retroperitoneal lymph node dissection; XRT, radiation.

These findings provide several important insights into SEMS trial data that are useful for patient counseling. First, the possibility of increasing effectiveness of RPLND by completing a bilateral template resection and limiting retrograde ejaculate through nerve-sparing techniques would further strengthen the value of this treatment option for patients with stage IIA seminoma. Second, while reports of cardiovascular toxicity after XRT are varied in the literature, reduction of such negative effects through subdiaphragmatic templates may support XRT as a comparable treatment option for these patients. Finally, in older patients with shorter life expectancies, disutilities from long-term treatment toxicities may be less important and consideration of management options with higher recurrence free survival rates is warranted.

In conclusion, RPLND was the least costly and most effective treatment strategy for stage IIA seminoma. In particular, long-term toxicity costs and disutilities associated with chemotherapy and XRT resulted in lower cost-effectiveness for these 2 approaches. These findings support clinical guideline consideration of including RPLND as a treatment option for well selected patients with stage IIA seminoma.