PURPOSE Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high... more PURPOSE Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP have demonstrated improved results. In this study, we assessed sRP functional outcomes and complications, comparing robotic and open approaches. MATERIALS AND METHODS We retrospectively collected data of sRP for recurrent prostate cancer (PCa) after local non-surgical treatment at 18 tertiary referral centers, from 2000 to 2016. The Clavien-Dindo classification was employed to classify complications. Complications and functional outcomes were evaluated in a uni- and multivariable analysis. RESULTS We included 395 sRP (n=186 open; n=209 robotic). The robotic-sRP yielded lower BL (p<0.0001) and shorter HS (p<0.0001). No significant differences emerged in major (10.1%, p=0.16) and overall complications (34.9%, p=0.67), including an overall low risk of rectal injuries and fistulas (1.58% and 2.02% respectively); however, anastomotic stricture was more frequent for open-sRP (16.57% vs 7.66%; p<0.01). Overall 24.6% had severe (≥3pads/day) incontinence (12 or 6mo). On multivariable analysis robotic-sRP was an independent predictor for continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature and absence of standardized surgical technique. CONCLUSIONS In a contemporary series, sRP showed a low risk of major complications and better functional outcomes than previously reported. Robotic-sRP may reduce anastomotic strictures, blood loss, and hospital stay, and improve continence outcomes.
ObjectiveTo investigate the functional and quality of life (QoL) outcomes of treatments for local... more ObjectiveTo investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision‐making.Patients and MethodsMen aged 50–69 years diagnosed with localised prostate cancer by prostate‐specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external‐beam radiotherapy (EBRT) with concurrent androgen‐deprivation therapy (ADT) and 77 low‐dose‐rate brachytherapy (BT, not a randomised treatment). Patient‐reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores.ResultsTreatment‐received analyses revealed different impacts of treatments ove...
Urologic Oncology: Seminars and Original Investigations, 2021
BACKGROUND Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and h... more BACKGROUND Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.
Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antig... more Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. Objectives To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50–69 years. Design A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. Setting Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. Participants Between 2001 and 2009, 228,966 men aged 50–69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT...
Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to estab... more Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0–2.95 ng/mL or 3.0–19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. Primary endpoints were randomization rates and intervention adherence (blinded assessment of metabolites) at 6 months with secondary endpoints of acceptability (from interviews), safety, weight, blood pressure, and PSA. A total of 133 of 469 (28.4%) men approached agreed to be randomized and 132 were followed-up (99.2%). Mean lycopene was 1.28 [95% confidence intervals (CI), 1.09–1.50, P ...
Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability... more Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the ProtecT RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Population-based cluster-randomization created a prospective study of PSA-testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. The prospective study (82,430 men PSA-tested) represented healthy men likely to respond to a screening invitation. The extended comprehensive-cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinicall...
Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PC... more Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of ...
Background The comparative effectiveness of treatments for prostate cancer that is detected by pr... more Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 ...
Background Robust data on patient-reported outcome measures comparing treatments for clinically l... more Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effec...
PURPOSE Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high... more PURPOSE Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP have demonstrated improved results. In this study, we assessed sRP functional outcomes and complications, comparing robotic and open approaches. MATERIALS AND METHODS We retrospectively collected data of sRP for recurrent prostate cancer (PCa) after local non-surgical treatment at 18 tertiary referral centers, from 2000 to 2016. The Clavien-Dindo classification was employed to classify complications. Complications and functional outcomes were evaluated in a uni- and multivariable analysis. RESULTS We included 395 sRP (n=186 open; n=209 robotic). The robotic-sRP yielded lower BL (p<0.0001) and shorter HS (p<0.0001). No significant differences emerged in major (10.1%, p=0.16) and overall complications (34.9%, p=0.67), including an overall low risk of rectal injuries and fistulas (1.58% and 2.02% respectively); however, anastomotic stricture was more frequent for open-sRP (16.57% vs 7.66%; p<0.01). Overall 24.6% had severe (≥3pads/day) incontinence (12 or 6mo). On multivariable analysis robotic-sRP was an independent predictor for continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature and absence of standardized surgical technique. CONCLUSIONS In a contemporary series, sRP showed a low risk of major complications and better functional outcomes than previously reported. Robotic-sRP may reduce anastomotic strictures, blood loss, and hospital stay, and improve continence outcomes.
ObjectiveTo investigate the functional and quality of life (QoL) outcomes of treatments for local... more ObjectiveTo investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision‐making.Patients and MethodsMen aged 50–69 years diagnosed with localised prostate cancer by prostate‐specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external‐beam radiotherapy (EBRT) with concurrent androgen‐deprivation therapy (ADT) and 77 low‐dose‐rate brachytherapy (BT, not a randomised treatment). Patient‐reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores.ResultsTreatment‐received analyses revealed different impacts of treatments ove...
Urologic Oncology: Seminars and Original Investigations, 2021
BACKGROUND Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and h... more BACKGROUND Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.
Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antig... more Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. Objectives To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50–69 years. Design A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. Setting Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. Participants Between 2001 and 2009, 228,966 men aged 50–69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT...
Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to estab... more Epidemiologic studies suggest that diet can alter prostate cancer risk. This study aimed to establish the feasibility and acceptability of dietary modification in men at increased risk of prostate cancer. Men were invited with a PSA level of 2.0–2.95 ng/mL or 3.0–19.95 ng/mL with negative prostate biopsies. Randomization (3 × 3 factorial design) to daily green tea and lycopene: green tea drink (3 cups, unblinded) or capsules [blinded, 600 mg flavan-3-ol ()-epigallocatechin-3-gallate (EGCG) or placebo] and lycopene-rich foods (unblinded) or capsules (blinded, 15 mg lycopene or placebo) for 6 months. Primary endpoints were randomization rates and intervention adherence (blinded assessment of metabolites) at 6 months with secondary endpoints of acceptability (from interviews), safety, weight, blood pressure, and PSA. A total of 133 of 469 (28.4%) men approached agreed to be randomized and 132 were followed-up (99.2%). Mean lycopene was 1.28 [95% confidence intervals (CI), 1.09–1.50, P ...
Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability... more Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the ProtecT RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Population-based cluster-randomization created a prospective study of PSA-testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. The prospective study (82,430 men PSA-tested) represented healthy men likely to respond to a screening invitation. The extended comprehensive-cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinicall...
Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PC... more Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of ...
Background The comparative effectiveness of treatments for prostate cancer that is detected by pr... more Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 ...
Background Robust data on patient-reported outcome measures comparing treatments for clinically l... more Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effec...
Uploads
Papers by David Gillatt