Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy

Abstract

Background: Salvage radiotherapy (SRT) is an established treatment for men with biochemical recurrence following radical prostatectomy (RP). There are several risk factors associated with adverse outcomes; however, the value of postoperative prostate-specific antigen (PSA) kinetics is less clear in the ultrasensitive PSA era. Objective: To characterize the impact of PSA kinetics on outcomes following SRT and generate nomograms to aid in identifying patients with an increased risk of adverse clinical outcomes. Design, setting, and participants: A multi-institutional analysis was conducted of 1005 patients with prostate cancer treated with SRT after RP, with a median followup of 5 years. Outcome measurements and statistical analysis: Variables examined include immediate postoperative PSA, postoperative PSA doubling time (DT), and pre-SRT PSA, in addition to previously identified predictive factors. Multivariable survival analyses were completed using Fine-Gray competing risk regression. Rates of biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were estimated by the cumulative incidence method. Nomograms were generated from multivariable competing risk regression with bootstrap cross-validation. Results and limitations: Factors associated with BF after SRT include PSA DT <6 mo, initial postoperative PSA 0.2 ng/ml, higher pre-SRT PSA, lack of androgen deprivation therapy, a higher Gleason score (GS), negative margins, seminal vesicle invasion, lack of pelvic nodal radiation, radiation total dose <66 Gy, a longer RP to SRT interval, and older age (p < 0.05 for each). Factors associated with DM include PSA DT <6 mo,

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Is Associated with Improved Oncological Outcome in Men Treated with Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer

“…However, Ghadjar et al [24] recently showed that the biochemical progression rate after SRT between patients who underwent 64 or 70 Gy to the prostate bed without hormonal therapy for BCR PCa did not differ significantly. Second, it is known that PSA doubling time is significantly associated with impaired oncological outcome after SRT [25]. In our study, however, we were not able to include PSA doubling time as a variable in the case-control matching study due to too many missing cases (231/610 patients [38%]).…”

Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage

“…The perception among radiation oncologists and urologists that SRT is equivalent to ART might lead to a delay of referral to SRT with higher PSA and subsequently worse prognosis [ 14 ]. It is important to stress that the presumed equivalence is for early SRT (hazard ratio for biochemical failure of 1.41 for PSA before SRT of ≤0.2 ng/mL vs. >0.2–0.49 ng/mL in a recent study from Campbell et al) [ 15 ]. This caveat holds especially for high-risk features such as GS 8–10 [ 16 ].…”

External validation of nomograms for salvage radiotherapy after radical prostatectomy

“…Campbell et al. [2] developed nomograms predicting survival, and recently integrated PSA kinetics into these models. The aim of this study was to validate these nomograms in a European cohort with and without inclusion of patients with pN1 disease.…”

“…Follow-up, progression definitions, and timing for imaging and treatment decisions are mainly based on PSA levels and PSA kinetics in daily clinical practice. Campbell et al [2] developed nomograms predicting survival, and recently integrated PSA kinetics into these models. The aim of this study was to validate these nomograms in a European cohort with and without inclusion of patients with pN1 disease.…”

“…We examined our review-board-approved institutional cohort, and identified 434 patients who underwent robot-assisted RP between 2006 and 2019 and who subsequently received sRT for biochemical failure between 2006 and 2020. In their developmental study [2], Campbell et al excluded pN1 patients from the cohort. We decided to run the models in our overall cohort and in the cohort without pN1 patients separately.…”