Taimur T Shah1, Abi Kanthabalan2, Marjorie Otieno2, Menelaos Pavlou3, Rumana Omar3, Sola Adeleke4, Francesco Giganti5, Chris Brew-Graves6, Norman R Williams2, Jack Grierson2, Haroon Miah2, Amr Emara7, Athar Haroon8, Arash Latifoltojar9, Harbir Sidhu10, Joey Clemente2, Alex Freeman11, Clement Orczyk12, Ashok Nikapota13, Tim Dudderidge14, Richard G Hindley15, Jaspal Virdi16, Manit Arya17, Heather Payne18, Anita Mitra18, Jamshed Bomanji19, Mathias Winkler20, Gail Horan21, Caroline M Moore12, Mark Emberton12, Shonit Punwani10, Hashim U Ahmed20. 1. 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. Electronic address: t.shah@imperial.ac.uk. 2. Division of Surgery and Interventional Sciences, University College London, London, UK. 3. Department of Statistical Science, University College London, London, UK. 4. Division of Medicine, Faculty of Medicine, University College London, London, UK; Department of Oncology, King's College London, London, UK; Department of Oncology, Maidstone and Tunbridge Wells Hospital, Maidstone, UK; School of Cancer & Pharmaceutical Sciences, King's College London, Queen Square, London WC1N 3BG, UK; High Dimensional Neurology, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, UK. 5. Division of Surgery and Interventional Sciences, University College London, London, UK; Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK. 6. Division of Medicine, Faculty of Medicine, University College London, London, UK. 7. Department of Urology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK; Urology Department, Ain Shams University Hospitals, Cairo, Egypt. 8. Department of Nuclear Medicine, St. Bartholomew's Hospital, Barts Health NHS Trust, London, UK; Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, UK. 9. Division of Medicine, Faculty of Medicine, University College London, London, UK; Department of Radiology, Royal Marsden NHS Foundation Trust, London, UK. 10. Division of Medicine, Faculty of Medicine, University College London, London, UK; Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK. 11. Department of Histopathology, University College London Hospital NHS Foundation Trust, London, UK. 12. Division of Surgery and Interventional Sciences, University College London, London, UK; Department of Urology, University College London Hospital NHS Foundation Trust, London, UK. 13. Sussex Cancer Centre. Royal Sussex County Hospital, Brighton, UK. 14. Department of Urology, University Hospital Southampton NHS Trust, Southampton, UK. 15. Department of Urology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK. 16. Department of Urology, The Princess Alexandra Hospital NHS Trust, Harlow, UK. 17. Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK. 18. Department of Oncology, University College London and University College London Hospital NHS Foundation Trust, London, UK. 19. Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, UK. 20. 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. 21. Department of Oncology, Queen Elizabeth Hospital, Kings Lynn, UK.
Abstract
BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The 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. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128.
BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The 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. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128.
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