An emerging, alternative treatment strategy is salvage focal therapy, using high-intensity focussed ultrasound (HIFU) or cryotherapy. Both aim to ablate only the areas of recurrent cancer within the prostate, and crucially may therefore offer improved continence and erectile function.4 This strategy makes sense as in the majority of cases the recurrent tumour is localised to the original index lesion.5 Nonetheless, planning for salvage focal therapy requires accurate disease localisation. The role of MRI for this purpose is not well understood, though image interpretation post-radiotherapy is known to be difficult owing to factors like gland atrophy and diffuse low T2 signal intensity.6
The phase II FORECAST (FOcal RECurrent Assessment and Salvage Treatment, NCT01883128) trial was designed to assess i) the accuracy of multiparametric MRI in the detection of radiorecurrent disease; and ii) the functional and oncological outcomes after salvage focal therapy.7
181 patients were recruited from 6 UK centres with a suspicion of recurrent disease level after external beam radiotherapy or interstitial low-dose-rate or high-dose-rate brachytherapy with or without neoadjuvant/adjuvant ADT. MRI was found to have a high sensitivity of 94% but, unlike in the primary setting, a low NPV of 46% due to the high prevalence of disease (80%). These data are in keeping with the notion that those with a rising PSA post-radiotherapy are very likely to harbour residual or recurrent cancer. When a lesion was visualised, MRI-targeted biopsies missed six cancers (8%) that were detected on template mapping biopsy. Conversely, four cancers (6%) were missed on systematic transperineal template prostate mapping biopsy. Thus, in an ideal setting, both targeted and systematic biopsies should be performed to maximise cancer detection.
93 patients subsequently underwent either HIFU for posterior disease (n=64, 69%), or cryotherapy (n=29, 31%) for anterior disease, previous brachytherapy use, or those with prostatic calcifications. Unique to the FORECAST trial was that local cytoreductive multi-modal treatment was given to 20 men (22%) who had nodal or metastatic disease, as detected by 18F-Choline PET/CT and/or bone scan. The remaining 73 (78%) had localised disease only. Pad-usage at 1-year was 16%, and 64% had erections sufficient for penetrative sexual activity. Progression-free survival was 66% at 24 months with no cancer-specific deaths.
These results together allow us to define better the paradigm for managing patients with radiorecurrent disease. Multiparametric MRI and MRI-targeted biopsy are able to detect cancer with good sensitivity and specificity, and both are needed for accurate disease localisation and characterisation. Whole body imaging is also vital in determining disease status as we have shown 1 in 4 may harbour nodal or metastatic disease. Although FORECAST was conceived in the era of 18F-Choline PET/CT, current practice would advocate the use of PSMA PET/CT instead. Crucially, identification of extra-prostatic disease would allow the delivery of multimodal therapy combining systemic and local treatment, whilst those with isolated prostatic recurrence could undergo local treatment alone.
Our data show that salvage focal ablation with HIFU and cryotherapy can achieve good oncological control whilst minimising the toxicity accompanies SRP. Although SRP would still have a role for high volume disease in younger men, the FORECAST trial data suggest a focal ablative approach should be an alternative to ADT in those that unsuitable or unwilling to undergo SRP.
Written by: Alexander Light1,2 Hashim U. Ahmed1,2,3 Taimur T. Shah1,2,3
- Imperial Prostate, Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, UK
- Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London UK
- Division of Surgery and Interventional Sciences, University College London, London, UK
- Zumsteg ZS, Spratt DE, Romesser PB, et al. The natural history and predictors of outcome following biochemical relapse in the dose escalation era for prostate cancer patients undergoing definitive external beam radiotherapy. Eur Urol. 2015;67(6):1009-1016.
- Chade DC, Shariat SF, Cronin AM, et al. Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration. Eur Urol. 2011 Aug;60(2):205-10.
- Golbari NM, Katz AE. Salvage Therapy Options for Local Prostate Cancer Recurrence After Primary Radiotherapy: a Literature Review. Curr Urol Rep. 2017;18(8):63.
- Reddy D, Peters M, Shah TT, et al. Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience. Eur Urol. 2022;81(4):407-413.
- Pucar D, Hricak H, Shukla-Dave A, et al. Clinically significant prostate cancer local recurrence after radiation therapy occurs at the site of primary tumor: magnetic resonance imaging and step-section pathology evidence. Int J Radiat Oncol Biol Phys. 2007 Sep 1;69(1):62-9.
- Gaur S and Turkbey, B. Prostate MR Imaging for Posttreatment Evaluation and Recurrence. Radiol Clin North Am. 2018;56(2):263-275.
- Shah TT, Kanthabalan A, Otieno M, et al. Magnetic Resonance Imaging and Targeted Biopsies Compared to Transperineal Mapping Biopsies Before Focal Ablation in Localised and Metastatic Recurrent Prostate Cancer After Radiotherapy. Eur Urol. 2022:S0302-2838(22)01664-5.
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