ASCO 2021: MRI and Targeted Biopsies Compared to Transperineal Mapping Biopsies For Targeted Ablation In Recurrent Prostate Cancer After Radiotherapy: The FORECAST Trial

(UroToday.com)  Radiotherapy and radical prostatectomy are common and guideline-recommended treatment for patients with localized prostate cancer. With each treatment approach, the risk of disease recurrence is non-negligible. For men who are initially treated with radiotherapy, most recurrences are managed with systemic androgen deprivation therapy with the associated systemic toxicity and subsequent development of castration resistance. An alternative is salvage local therapy. However, salvage prostatectomy is associated with substantially increased rates of side effects. A more recently adopted approach is salvage focal therapy, an approach which may be effective while limiting toxicity. In the Prostate, Testicular, Penile Poster Discussion session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Shah presented the results of the FORECAST trial, examining MRI and targeted biopsy compared to transperineal biopsy to inform ablation for recurrent prostate cancer following initial radiotherapy.

The FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128) assessed MRI and targeted biopsy compared to transperineal biopsy to inform ablation for men with radio recurrent cancer. To do so, the authors compared the accuracy of multi-parametric MRI (mp-MRI) and MRI-targeted biopsy in identifying areas of recurrent cancer to a transperineal template prostate mapping (TTPM) biopsy among 181 patients across 6 different clinical sites in the United Kingdom in an initial phase conducted between April 2014 and Jan 2018. Subsequently, they assessed the functional and cancer control outcomes of focal ablation of areas of intraprostatic recurrence in 93 patients with localised or metastatic cancer (using cryotherapy or HIFU).

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The primary outcomes were sensitivity of mpMRI and MRI-targeted biopsies (for part one) and urinary continence after focal ablation (for part two). A key secondary outcome was progression free survival (PFS) defined as no new metastases or hormone use (localised group only), or chemotherapy or further local treatment.

Among the 181 men with suspicion of recurrence following radiotherapy enrolled in the first portion, re-staging whole-body imaging using Choline PET and Bone Scan was performed. This demonstrated localised disease in 128 (71%), nodal disease only in 13 (7%) and metastatic disease in 38 (21%). Assessing the primary outcome, the sensitivity of MRI-targeted biopsy was 92% (95%CI 83-97%) compared to the gold standard of transperineal template prostate mapping biopsy. Specificity, and positive and negative predictive values were 75% (95%CI 45-92%), 94% (95%CI 86-98%) and 65% (95%CI 38-86%), respectively. Notably, 4/72 (6%) cancers were missed on TTPM biopsies alone and 6/72 (8%) were missed on MRI-targeted biopsies alone.

Utilizing a threshold of 4-5 on the Likert scale (rather than 3-5) to define a positive, the overall sensitivity of mpMRI was 81% (95%CI 73-88%) with specificity, and positive and negative predictive values of 88% (95%CI 73-98%), 96% (95%CI 90-99%) and 57% (95%CI 42-70%), respectively.

In the second portion of the study, among the 93 men undergoing focal ablation, urinary continence was preserved in 78/93 (84%). However, five of 93 men (5%) experienced a CTCAE grade 3+ adverse event though there were no rectal injuries. Over a median follow-up of 27.8 [SD 1.3] months, progression-free survival was 66% [95% CI 54-75] at 24-months with metastases-free survival of 80% [95%CI 68–88] at 24-months among the 32 men with localized disease at the time of treatment. There were no cancer specific deaths.

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The authors conclude that prostate mpMRI with MRI-targeted biopsies can accurately detect and localise recurrent prostate cancer following radiotherapy. Following this disease characterization, focal ablation is a reasonable treatment approach with good cancer control and low rates of incontinence.

Presented by: Taimur T. Shah, MBBS, BSc (Hons), FRCS (Urol) PhD, Imperial College London, Division of Surgery

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Contact: @WallisCJD on Twitter at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021