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Optimizing anti-androgen treatment use among men with pathologic lymph-node positive prostate cancer treated with radical prostatectomy: the importance of postoperative PSA kinetics

Subjects

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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Fig. 1
Fig. 2: Identification of three risk groups in pN1 men.
Fig. 3: Metastasis-free survival plots.
Fig. 4: Cancer-specific survival plots.
Fig. 5: Overall survival plots.

Data availability

Data are available to interested parties on request from the corresponding author.

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Contributions

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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Correspondence to Akshay Sood or Firas Abdollah.

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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 (2022). https://doi.org/10.1038/s41391-022-00572-z

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