Abstract
Background
Optimal postsurgical management of prostate cancer (PCa) patients with nodal metastasis at the time of radical prostatectomy remains unclear. We sought to examine the role of postoperative PSA kinetics and pathologic tumor characteristics in guiding additional hormonal therapy use in pN1 men.
Methods
In total, 297 pN1 PCa patients treated with radical prostatectomy and ePLND between 2002 and 2018 were identified within our prospectively maintained institutional cancer data-registry. Following surgery, these patients were managed with either immediate androgen deprivation therapy (iADT) or observation with deferred ADT (dADT). The former was defined as ADT given within ≤6 months of surgery and the latter as >6 months. The primary outcome was metastasis. Regression-tree analysis was used to stratify patients into novel risk-groups based on post-prostatectomy tumor characteristics and PSA kinetics and the corresponding metastasis risk. Multivariable Cox regression analyses tested the impact of iADT versus observation ± dADT on metastasis, cancer-specific mortality, and overall mortality within each risk-group separately.
Results
The median follow-up was 6.1 years (IQR 3.2–9.0). Regression-tree analysis stratified patients into 3 novel risk-groups (Harrell’s C-index 0.79) based on PSA-nadir and time to biochemical failure: group 1 (low-risk) included patients with time to biochemical recurrence >6 months (n = 115), while groups 2 and 3 included patients with biochemical failure within ≤6 months with a postoperative PSA-nadir <1.05 ng/mL (group 2 [intermediate-risk], n = 125) or ≥1.05 ng/mL (group 3 [high-risk], n = 57), respectively. No other patient or tumor characteristics were significant for risk stratification. Within each risk-group, the 10-year metastasis-free survival rates with iADT versus observation ± dADT use were: group 1, 100% versus 95.4% (Log-rank p = 0.738), group 2, 80.6% versus 53.5% (Log-rank p = 0.016), and group 3, 41.5% versus 0% (Log-rank p = 0.015), respectively. Adjusted Cox regression analyses confirmed the benefit of iADT utilization in reducing metastasis in group 2 (p = 0.029) and group 3 (p = 0.008) patients, with no benefit for group 1 patients (p = 0.918). Similar results were noted for cancer-specific and overall mortality.
Conclusions
Following radical prostatectomy, early postoperative PSA kinetics may provide valuable information for guiding the timing of ADT initiation—this may reduce over- and undertreatment of pN1 PCa men.
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Data availability
Data are available to interested parties on request from the corresponding author.
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Conception and design: AS, FA. Acquisition of data: LTZ, MB, MS. Analysis and interpretation of data: AS, FA. Drafting of manuscript: AS, LTZ, MB, MS, JRA, RG, JOP, CGR, MM, FA. Critical revision of the manuscript for important intellectual content: AS, FA. Statistical analysis: JK. Funding: MM. Administrative, technical, or material support: MM. Other: -.
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Sood, A., Zhang, L.T., Keeley, J. et al. Optimizing anti-androgen treatment use among men with pathologic lymph-node positive prostate cancer treated with radical prostatectomy: the importance of postoperative PSA kinetics. Prostate Cancer Prostatic Dis 27, 58–64 (2024). https://doi.org/10.1038/s41391-022-00572-z
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DOI: https://doi.org/10.1038/s41391-022-00572-z