F‐SHARP: a Phase I/II trial of focal salvage high‐dose‐rate brachytherapy for Radiorecurrent prostate cancer

• Published in: BJU international Vol. 133; no. 2; pp. 188 - 196
• Main Authors: Solanki, Abhishek A., Yoo, Ryan K., Adams, William, Davicioni, Elai, Mysz, Michael L., Shea, Steven, Gupta, Gopal N., Showalter, Timothy, Garant, Aurelie, Hentz, Courtney, Farooq, Ahmer, Baldea, Kristin, Small, William, Harkenrider, Matthew M.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2024
• Subjects: Adenocarcinoma; biochemical recurrence; Biopsy; Brachytherapy; Brachytherapy - adverse effects; Brachytherapy - methods; Cancer therapies; Computed tomography; decipher; focal; high‐dose‐rate; Humans; intraprostatic recurrence; Magnetic resonance imaging; Male; Metastases; Neoplasm Recurrence, Local - pathology; Patients; Positron emission tomography; Positron Emission Tomography Computed Tomography; Prostate cancer; Prostatic Neoplasms - pathology; Quality of Life; Radiation therapy; radiorecurrence; Radiotherapy Dosage; re‐irradiation; salvage local therapy; Salvage Therapy - methods; Terminology; Tomography; Toxicity; Transcriptomics; high-dose-rate; prostate cancer; focal; biochemical recurrence; intraprostatic recurrence; radiorecurrence; decipher; brachytherapy; re-irradiation; salvage local therapy
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/bju.16150

Background Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high‐dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the ‘focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy’ (F‐SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. Study Design The F‐SHARP is a multi‐institutional two‐stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. Endpoints The primary endpoint is the acute radiation‐related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease‐specific and overall survival, and health‐related quality of life, as measured by the International Prostate Symptom Score and 26‐item Expanded Prostate Cancer Index Composite instruments. Patients and Methods Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1–3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long‐term toxicity profile, quality of life, and compare single‐ vs multi‐fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.