Radical Prostatectomy After Radical Radiotherapy

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) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. Interventions The interventions were active monitoring, radical prostatectomy and radical radiotherapy. Trial primary outcome measure Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. Secondary outcome measures Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. Results There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy’s impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). Limitations A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. Conclusions At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. Trial registration Current Controlled Trials ISRCTN20141297. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

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Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial

BMC Cancer ◽

10.1186/s12885-020-07276-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

S. Sanghera ◽

◽

S. Mohiuddin ◽

J. Coast ◽

K. Garfield ◽

...

Keyword(s):

Prostate Cancer ◽

Sensitivity Analysis ◽

Cost Effectiveness ◽

Radical Prostatectomy ◽

Lifetime Cost ◽

Radical Radiotherapy ◽

Grade Group ◽

Active Monitoring ◽

Link Type ◽

Risk Prostate Cancer

Abstract Background Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. Methods A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. Results Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D’Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D’Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D’Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. Conclusion Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. Trial registration Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

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Effect of Comorbidity on Prostate Cancer–Specific Mortality: A Prospective Observational Study

Journal of Clinical Oncology ◽

10.1200/jco.2016.70.7794 ◽

2017 ◽

Vol 35 (31) ◽

pp. 3566-3574 ◽

Cited By ~ 13

Author(s):

Prabhakar Rajan ◽

Prasanna Sooriakumaran ◽

Tommy Nyberg ◽

Olof Akre ◽

Stefan Carlsson ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Observational Study ◽

Population Based ◽

Tumor Characteristics ◽

Radical Radiotherapy ◽

Data Set ◽

Treatment Type ◽

Specific Mortality ◽

Type Radical

Purpose To determine the effect of comorbidity on prostate cancer (PCa)–specific mortality across treatment types. Patients and Methods These are the results of a population-based observational study in Sweden from 1998 to 2012 of 118,543 men who were diagnosed with PCa with a median follow-up of 8.3 years (interquartile range, 5.2 to 11.5 years) until death from PCa or other causes. Patients were categorized by patient characteristics (marital status, educational level) and tumor characteristics (serum prostate-specific antigen, tumor grade and clinical stage) and by treatment type (radical prostatectomy, radical radiotherapy, androgen deprivation therapy, and watchful waiting). Data were stratified by Charlson comorbidity index (0, 1, 2, or ≥ 3). Mortality from PCa and other causes and after stabilized inverse probability weighting adjustments for clinical patient and tumor characteristics and treatment type was determined. Kaplan-Meier estimates and Cox proportional hazards regression models were used to calculate hazard ratios. Results In the complete unadjusted data set, we observed an effect of increased comorbidity on PCa-specific and other-cause mortality. After adjustments for patient and tumor characteristics, the effect of comorbidity on PCa-specific mortality was lost but maintained for other-cause mortality. After additional adjustment for treatment type, we again failed to observe an effect for comorbidity on PCa-specific mortality, although it was maintained for other-cause mortality. Conclusion This large observational study suggests that comorbidity affects other cause–mortality but not PCa-specific– mortality after accounting for patient and tumor characteristics and treatment type. Regardless of radical treatment type (radical prostatectomy or radical radiotherapy), increasing comorbidity does not seem to significantly affect the risk of dying from PCa. Consequently, differences in oncologic outcomes that were observed in population-based comparative effectiveness studies of PCa treatments may not be a result of the varying distribution of comorbidity among treatment groups.

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Variation in usage of radical prostatectomy and radical radiotherapy for men with locally advanced prostate cancer

Journal of Clinical Urology ◽

10.1177/2051415816681247 ◽

2017 ◽

Vol 10 (1_suppl) ◽

pp. 34-38 ◽

Cited By ~ 1

Author(s):

Luke Hounsome ◽

Ed Rowe ◽

Julia Verne ◽

Roger Kockelbergh ◽

Heather Payne

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Hormone Therapy ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Radical Radiotherapy ◽

Locally Advanced Prostate Cancer ◽

Comorbidity Score ◽

Radical Treatment ◽

Charlson Comorbidity Score

Locally advanced prostate cancer is defined as primary tumours extending outside the prostate gland to the surrounding tissues or seminal vesicles but without spread beyond the pelvic region. With radical treatment there is good prospect of cure. Radiotherapy in combination with hormone therapy is well established, but specific NICE guidelines have only recently been published. The guidelines recommend offering either radical prostatectomy (RP), possibly with adjuvant radiotherapy, or radical radiotherapy (RT) with neo-adjuvant hormone therapy as treatment for men with locally advanced prostate cancer. Given that guidelines on managing locally advanced prostate cancer have recently changed, we wanted to quantify the baseline variation in use of radical treatments for this patient group. Methods: Men with T3/T4 N0 M0 prostate cancer who were diagnosed in 2010–2012 were identified using data from the National Cancer Registration and Analysis Service (NCRAS). Data on age, ethnicity, deprivation, Charlson comorbidity score, Strategic Clinical Network (SCN) of residence, and treatments delivered were extracted. A multivariable logistic regression was undertaken to identify important variables. Results: Overall, 1692 (14%) of men in the cohort had a record of radical prostatectomy. A total of 6212 (52%) had a record of curative RT. In a regression model each decade increase in age yielded odds of 0.39 ( p < 0.001) for receiving radical treatment. Black men were only half as likely as white men to receive radical treatment (OR = 0.54; p < 0.001). Deprivation, comorbidity and SCN of residence had smaller effects. The variation observed in radical treatment between SCNs largely disappeared once the multiple variables were accounted for. Conclusion: Radical treatments vary by 71% to 85% between networks for men aged 60–69 years. Given that men >80 years made up 12% of the study population and only 6% had a Charlson comorbidity score >0, there is a possibility that some men with ‘clinically significant’ disease are undertreated.

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