Salvage for radiorecurrent prostate cancer

Abstract

Patients primarily treated with radiotherapy for prostate cancer are at risk of recurrent disease. These recurrences, if confined to the prostate, can be curatively treated using salvage. Several salvage techniques are available, of which salvage radical prostatectomy, cryotherapy, high intensity focussed ultrasound (HIFU) and brachytherapy (low dose rate [LDR] or high dose rate [HDR]) are most frequently adopted. These techniques typically target the entire prostatic volume due to previous difficulties in assessing metastatic disease and adequate localisation of the recurrence. Previous radiation damage to surrounding organs at risk has made whole-gland salvage procedures associated with high severe toxicity, both of the gastro-intestinal (GI) and genitourinary (GU) tract, as well as erectile dysfunction. Furthermore, cancer control rates are disappointing, due to inaccurate assessment of prostate-confined disease. Developments in multiparametric MRI-techniques and PET-imaging have made it increasingly possible to accurately assess localised disease and exclude metastases. This has led to the increasing adoption of focal salvage, targeting only part of the prostate gland. Varying focal salvage techniques are described with approximately equal cancer control rates but seemingly favourable toxicity profiles compared to whole-gland salvage. This was also observed in a focal salvage I-125 brachytherapy series from the UMCU. It seems this also increased cost-effectiveness. If a recurrence is not eligible for focal salvage, restrictions in the dose levels for organs at risk are necessary to reduce the severe late toxicity associated with whole-gland salvage I-125 brachytherapy. Restrictions are currently based on primary brachytherapy, which are theoretically too lenient due to previous radiation damage. In the current thesis, restriction for whole-gland salvage I-125 brachytherapy were assessed. To summarise: to be able to prevent ≥grade 3 GU toxicity, bladder D2cc (minimal dose to the most irradiated 2cc of the structure its volume) should ideally be <70 Gy. To prevent other late GU toxicities, the urethral V100 (volume receiving 100% of the dose) should be <0.40 cc. Restrictions to prevent late severe GI toxicity were a D0.1cc <160 Gy, a D2cc <100 Gy and a V100 <0.38cc. These restrictions are indeed set lower than in the primary setting. Before being able to apply these restrictions, patients should be adequately selected. Failure rates for whole-gland salvage brachytherapy are high, indicating a role for prediction models assessing the most eligible patients. Using multivariable prediction models, it seems patients can be adequately selected using the disease free survival interval (DFSI) after primary therapy and their PSA-doubling time (PSADT) before salvage. Biochemical disease free survival (BDFS) >70% is achieved with a PSADT>30 months and a DFSI>60 months or other combinations. For survival, selection can be done using the PSADT. For focal salvage HIFU, the model model shows that the DFSI, pre-salvage PSA, PSADT, prostate volume and T-stage as assessed on MRI can adequately predict BDFS up to 3 years. In the most favourable risk group, 90% BDFS up to 3 years follow-up was attained. The use of the risk score can guide patient selection for focal salvage HIFU and possibly other focal salvage modalities.