Session Item

Comprehensive predictive models of long-term biochemical-relapse-free survival (bRFS) after post-prostatectomy salvage radiotherapy (SRT) are lacking. A previously realized radiobiology-based formula was adapted to incorporate the impact of pelvic node irradiation (PNI) and was applied to a multi-Institute cohort treated with SRT to estimate the long-term impact of PNI.

bRFS may be expressed by a Poisson-based equation ((K x (1- exp(-αeffD))CxPSA), including pre-SRT PSA, the radiosensitivity parameter αeff, the clonogen density C (assuming a pre-SRT PSA=1 ng/mL), the prescribed

2-Gy equivalent dose D, and a factor K=(1-BxλxPSA) representing the detrimental impact on post-SRT bRFS due to clonogens outside the irradiated volume at SRT, with λ being the recovery of bRFS obtainable with PNI. Data of 795 pT2-pT3a/pT3b, pN0/pN1/pNx patients (pts) treted in 8 Institutes with a 5-year minimum follow-up and a pre-RT PSA≤2 ng/mL were randomly split into training (n=528) and validation (n=267) cohorts; data of the training cohort were fitted by the least square method. Separate fits were performed on two class-risk groups, based on the most robust, clinically significant predictors resulting from a multi-variable Cox regression analysis. Model performances were compared against true data by calibration plots and tested in the validation group.

The median follow-up was 8.5 years, median pre-SRT PSA 0.54 ng/mL, median SRT EQD2 dose 72.6 Gy; 336/795 pts received PNI. The most clinically significant prognostic grouping identifying the high-risk cohort was found to be “pT3b and/or ISUP 4-5 Class”, as opposed to pT2/pT3a and ISUP 1-3 (low-risk group). Fits on the training cohort were successful with consistent best-fit parameters of: αeff=0.26/0.23Gy-1, C=10⁷, B=0.40/0.97, λ=0.87/0.41 for the low-risk (n=417) and high-risk (n=111) groups, respectively. The calibration was satisfactory (slope=0.79, R²=0.82). Performances were confirmed in the validation group (slope=0.91, R²=0.91). Results suggested an optimal SRT EQD2 dose in the range of 70 and 74 Gy for low- and high-risk groups, respectively. The estimated bRFS recovery obtainable with PNI corresponding to these dose levels is shown in the Figure: >5% for PSA>1 and 0.15 ng/mL in low-risk and high-risk pts, respectively, and >10% for high-risk pts with a pre-SRT PSA>0.25 ng/mL.

An explainable one-size-fits-all equation satisfactorily predicts long-term bRFS after SRT. Model parameters were obtained by fitting a large multi-centric cohort, and the model was independently validated. Results suggest that a significant (and rapidly increasing for rising pre-SRT PSA values) impact of PNI may be expected in patients with pT3b and/or ISUP4-5 disease at prostatectomy. The added value of PNI is, on the contrary, negligible in the low-risk cohort for pre-SRT values up to 1 ng/mL. A calculation tool for individual estimates is available.