Unravelling Salvage Re-irradiation for Locally Recurrent Prostate Cancer: Challenges and Complexities

The management of locally radiorecurrent prostate cancer after radical treatment with external beam radiotherapy (EBRT) presents challenges due to limited comparative data on salvage modalities and concerns regarding genitourinary and gastrointestinal toxicity. Patient selection for salvage therapy requires careful consideration of long-term toxicity, the metastatic disease development, and life expectancy. While androgen deprivation treatment (ADT) is commonly used, it can negatively impact patients' quality of life. Local salvage treatments such as salvage prostatectomy, reirradiation with brachytherapy (BT) or stereotactic body radiotherapy (SBRT), cryotherapy, and high-intensity focused ultrasound (HIFU) exist as alternative options but lack consensus recommendations. Imaging is crucial in distinguishing local recurrence from systemic disease. Computed tomography (CT) scans and bone scintigraphy have limitations in detecting local recurrence. Multiparametric magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron-emission tomography computed tomography (PSMA PET-CT) improve detection rates, especially at low prostate-specific antigen (PSA) levels. Radioresistance mechanisms including DNA repair activation, hypoxia, and clonal selection, may influence recurrence and response to salvage therapy. Additionally, novel antiandrogens show promise in enhancing salvage radiotherapy outcomes, though patient selection and toxicity management remain critical. Current guidelines provide limited recommendations for salvage treatment after radiotherapy, emphasizing the need for clinical trials. Patient selection criteria are limited pre-existing toxicities. This review focuses mainly on the salvage re-irradiation options available. In conclusion, the management of locally recurrent prostate cancer post-EBRT requires careful consideration of patient selection criteria and the salvage options available. Salvage reirradiation using high-dose-rate brachytherapy high dose-rate (HDR)-BT or SBRT provides similar biochemical control and more acceptable late toxicity. Further research is needed to determine optimal treatment strategies, the duration of ADT, and the benefits of focal therapy vs whole-gland treatment in this challenging patient population.