Part II | Chapter 8 170 Discussion This study provides two clinically useful multivariable prediction models for biochemical failure in patients with radiorecurrent prostate cancer treatedwith FS-HDR-BT. Model 1 can be used to support clinical decision-making and patient guidance at baseline, while model 2 could be used during follow-up to counsel patients regarding their prognosis and potentially adapt follow-up intensity accordingly. The predictors in both models and the direction of their effects were mostly as expected. Increased age was associated with a lower hazard of biochemical failure. Although causal inference is not applicable in prediction, this could be explained by the potentially longer disease-free survival interval (DFSI) between primary and salvage treatment, indicating more indolent tumours. DFSI was longer in elderly patients (median 92 versus 108 months for < 75 years versus ³ 75 years, respectively). Data on pre-salvage Gleason score is mostly lacking in our cohort, which hinders assessing this relation. Both a higher pre-salvage PSA level and larger GTV were associated with an increased hazard. Both indicate higher tumour load and were therefore expected to be correlated with biochemical failure. For pre-salvage PSADT, which was non-linearly related to the outcome, hazard decreased with longer doubling times. This was expected given previous reports.17 However, from approximately 32 months onward, the hazard increased slightly again, as displayed by a HR of 1.18 for PSADT’. PSADT was ³ 32 months in only 19 patients (12.7%). Median post-primary PSA nadir, post-salvage PSA nadir, and pre-salvage PSA were higher in these patients compared to those with a PSADT of < 32 months (1.1 vs 0.5 ng/mL, 0.9 vs 0.6 ng/mL, and 6.1 vs 4.6 ng/mL, respectively), but the percentage of patients classified as high-risk (NCCN) at primary treatment was comparable (39% vs 42%). Therefore, we have no clear explanation, and these findings might be caused by the limited sample size. Seminal vesicle involvement, which is a sign of extensive disease, was associated with an increased hazard of biochemical failure. A longer post-salvage time to PSA nadir was associated with a lower hazard, potentially reflecting tumour biology (a faster response after radiotherapy could be a sign of more malignant/dedifferentiated prostate cancer) as previously observed.31 Finally, a larger reduction in PSA level was protective of biochemical failure. Several studies have identified predictors for biochemical failure in patients with radiorecurrent prostate cancer treated with focal or whole-gland salvage high-intensity focused ultrasound (HIFU), low-dose rate brachytherapy (LDR-BT), and cryotherapy.17,32–34 However, it is questionable to what extent predictors from whole-gland salvage studies are applicable to focal salvage treatments. Spiess et al.33 reported a risk stratification model in a whole-gland salvage cryotherapy cohort (n = 132), using the Phoenix definition of biochemical failure. Upon multivariable analysis, post-salvage PSA nadir and pre-salvage Gleason score were identified as predictors for biochemical failure. PSA nadir was also identified as a predictor of biochemical failure after salvage whole-gland HIFU in a small cohort of 50 patients.34 Peters et al.17 showed that DFSI between primary and salvage treatment, T-stage before salvage, prostate volume (cm3), PSA, and PSADT were predictors of biochemical failure in patients treated with focal salvage HIFU. This model shows overlap with our model, indicating that pre-salvage PSA and PSADT are strong predictors for biochemical failure after
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