Jochem R N van der Voort van Zyp1, Matt Winkler2,3, Alison Falconer2,3, Marieke J van Son4,5,6, Max Peters2,1, Deepika Reddy2, Taimur T Shah2,7, Feargus Hosking-Jervis2, Stephen Robinson8, Jan J W Lagendijk1, Stephen Mangar3, Tim Dudderidge9, Stuart McCracken7, Richard G Hindley10, Amr Emara10, Raj Nigam11, Raj Persad12, Jaspal Virdi13,14, Henry Lewi15, Caroline Moore16,17, Clement Orczyk16,17, Mark Emberton16,17, Manit Arya2,3,13,14,17, Hashim U Ahmed2,3. 1. Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK. 2. Imperial Prostate, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK. 3. Imperial Urology, Imperial College Healthcare NHS Trust, London, UK. 4. Imperial Prostate, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK. M.J.vanSon-3@umcutrecht.nl. 5. Department of Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK. M.J.vanSon-3@umcutrecht.nl. 6. Department of Radiotherapy, University Medical Centre Utrecht, Utrecht, The Netherlands. M.J.vanSon-3@umcutrecht.nl. 7. Department of Urology, Sunderland Royal Hospital, City Hospital Foundation Trust, Sunderland, UK. 8. Division of Clinical Oncology, Department of Radiotherapy, Charing Cross Hospital, Imperial College London Healthcare NHS Trust, London, UK. 9. Department of Urology, University Hospital Southampton NHS Trust, Southampton, UK. 10. Department of Urology, Hampshire Hospitals & Ain Shams University Hospitals, Basingstoke, UK. 11. BMI Mount Alvernia Hospital, Guildford, Surrey, UK. 12. Department of Urology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK. 13. Department of Urology, Princes Alexandra Hospital NHS Trust, Harlow, UK. 14. Rivers Hospital, Essex, UK. 15. Springfield Hospital, Chelmsford, UK. 16. Department of Surgery and Interventional Sciences, University College London, and University College Hospital London, London, UK. 17. Department of Urology, UCLH NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies. METHODS: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28-83) and 62 (42-83) months, respectively. RESULTS: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9-87.3) than after focal therapy (72.8%, 95% CI 66.8-79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1-95.2 versus 97.5%, 95% CI 94-99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008). CONCLUSIONS: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.
BACKGROUND: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies. METHODS: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28-83) and 62 (42-83) months, respectively. RESULTS: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9-87.3) than after focal therapy (72.8%, 95% CI 66.8-79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1-95.2 versus 97.5%, 95% CI 94-99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008). CONCLUSIONS: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.