Development and internal validation of multivariable prediction models for biochemical failure after MRI-guided focal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

Abstract

Background and purpose: Magnetic resonance-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) for radiorecurrent prostate cancer (PCa) shows low toxicity rates. However, biochemical failure (BF) after treatment occurs frequently. We developed two prediction models for BF (Phoenix definition) with the aim of enhancing patient counselling before FS-HDR-BT and during follow-up. Materials and methods: A prospective cohort of 150 radiorecurrent PCa patients treated with FS-HDR-BT between 2013 and 2020 was used for model development and internal validation. Multivariable Cox Proportional Hazards regression was applied. For model 1, only pre-salvage variables were included as candidate predictors. For model 2, additional (post-)salvage characteristics were tested. After calibration, nomograms and webtools were constructed. Finally, three risk groups were identified.Results: Sixty-one patients (41%) experienced BF. At baseline (model 1), age, gross tumour volume, pre-salvage PSA, and pre-salvage PSA doubling time (PSADT) were predictive of BF. During follow-up (model 2), age, presalvage PSA and PSADT, seminal vesicle involvement, post-salvage time to PSA nadir, and percentage PSA reduction were predictive of BF. The adjusted C-statistics were 0.73 (95% CI: 0.66-0.81) and 0.84 (95% CI: 0.78-0.90), respectively, with acceptable calibration. Estimated 2-year biochemical disease-free survival for the low-, intermediate-, and high-risk groups were 84%, 70%, and 31% (model 1), and 100%, 71%, and 5% (model 2). Conclusion: Two models are provided for prediction of BF in patients with radiorecurrent PCa treated with FS-HDR-BT. Based on pre-and post-salvage characteristics, we are able to identify patients with a high risk of BF. These findings can aid patient counselling for FS-HDR-BT.

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

“…There exists one other published model by Willigenburg et al. [20] in the setting of salvage focal brachytherapy, but this has not been externally validated.…”

“…It will be useful to evaluate how novel radiological parameters may improve models. Between the models by Peters et al [7] and Willigenburg et al [20], radiological variables considered were prostate volume, lesion volume, and stage. However, these do not necessarily quantify the likelihood of radiorecurrent disease.…”

Value of Targeted Biopsies and Combined PSMA PET/CT and mp-MRI Imaging in Locally Recurrent Prostate Cancer after Primary Radiotherapy

“…The association between Gleason score and outcome after focal salvage is not clear: some studies find a correlation [53], but other studies do not [54,55]. Prediction models with a good performance are available, also in the setting of focal salvage HDR brachytherapy [56], in which other parameters have been described to be predictive of biochemical failure after focal salvage HDR brachytherapy for locally recurrent prostate cancer, such as gross tumor volume, pre-salvage PSA-value, and pre-salvage PSA doubling time [56]. Gleason score seems to be of limited added value, due to the inconclusive findings in the literature.…”

Single-fraction high-dose-rate brachytherapy: a scoping review on outcomes and toxicities for all disease sites

“…For patients treated with salvage treatment, two studies reported on outcomes with 2-year PSA control rates ranging from 42% to 59%. These results, similar to the definitive setting, demonstrated less than ideal outcomes with single-fraction treatment [ 12 , 16 ].…”

“…Eight studies treated patients with androgen deprivation therapy treatment over a range between 3 and 36 months. In the definitive therapy series, median follow-up ranged from 20 to 72 months, while in the salvage series it ranged from 25 to 26 months [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”