Therapies for Clinically Localized Prostate Cancer [Entered Retrospectively]

Project Summary Title and Description

Therapies for Clinically Localized Prostate Cancer [Entered Retrospectively]
Structured Abstract Objective. To identify new information that updates findings from previous AHRQ and AUA funded reviews evaluating therapies for clinically localized prostate cancer (CLPC). Sources. Bibliographic databases (2013-January 2020);; systematic reviews Methods. Controlled studies of CLPC (T1-T3a) treatments with duration ≥5 years for mortality and metastases and ≥1 year for quality of life and harms. Interventions included watchful waiting (WW), active surveillance or monitoring (AS, AM), androgen deprivation (AD), focal and whole gland therapies or combinations. We evaluated how patient and tumor characteristics modify treatment outcomes and how provider/hospital characteristics modify effectiveness of radical prostatectomy (RP) compared to other therapies. One investigator rated risk of bias (ROB), extracted data, and assessed certainty of evidence; a second checked accuracy. We analyzed English-language studies with low or medium ROB. We incorporated findings from RCTs identified in the 2014 AHRQ and 2016 AUA funded reviews if new RCTs provided information on the same intervention comparison. We derived thresholds defining “small”, “moderate” and “large” effect, summarize key findings from prior reviews and the impact of new research. Results. We identified 67 eligible references; 17 unique RCTs. Among clinically, rather than PSA detected CLPC, WW may increase overall and prostate-cancer mortality, and metastases versus RP at 20+ years. Urinary and erectile dysfunction were lower with WW versus RP. WW‘s effect on mortality may have varied by tumor risk and age but not by race, health status, comorbidities or PSA. AM probably results in little to no difference in overall or prostate-cancer mortality in PSA detected CLPC versus RP or EBR plus AD through 10 years regardless of tumor risk. Metastases were infrequent but slightly higher with AM. Harms were greater with RP than AM and mixed between EBR plus AD versus AM. 3D-Conformal EBR and AD plus low-dose-rate brachytherapy (BT) provided a small reduction in all-cause mortality versus 3D-CRT and AD but little to no difference on metastases. EBR plus AD versus EBR alone may have resulted in a small reduction in overall and prostate-cancer mortality and metastases in higher risk disease but may increase sexual harms. EBR plus initiating neoadjuvant AD versus EBR plus initiating concurrent AD may result in little to no difference in mortality at 12 years and genitourinary toxicity at 3 years. Conventionally fractionated EBR versus ultra-hypofractionated EBR may result in little to no difference in mortality and metastasis at 5 years and urinary and bowel toxicity at 2 years. Limited evidence suggested that AS results in fewer harms than photodynamic therapy and laparoscopic RP resulted in more harms than robotic-assisted RP. There was little to no information on long-term comparative effectiveness of other treatments. No studies evaluated WW or AS in screen detected CLPC or MRI for risk assessment or were conducted since effective pharmacologic therapies for advanced disease. No studies assessed provider or hospital factors of RP comparative effectiveness. Conclusions. RP reduces mortality versus WW in clinically detected CLPC but causes more harms. Effectiveness may be limited to younger men, those with intermediate risk disease and requires many years to occur. AM results in little to no mortality difference versus RP or EBR plus AD. EBR plus AD reduces mortality versus EBR alone in higher risk CLPC but may worsen sexual function. Adding low-dose-rate BT to 3D-Conformal EBR and AD may reduce mortality in higher risk CLPC. Little information exists on other treatments or the effects of patient, tumor and provider factors. Large, long-term RCTs in PSA-detected and MRI staged CLPC are needed.
Authors of Report
Methodology description
Notes Data entered retrospectively. Downloadable data files include the following data: PICOTS, ROB assessments, outcomes and harms. Data are organized by intervention type.
Funding Source
AHRQ Contract HHSA290201500008I

Key Questions

1. KQ 1: What are the comparative effectiveness and harms of CLPC therapies? 1) Watchful waiting 2) Active surveillance/Active monitoring 3) Androgen deprivation therapy (ADT) 4) Focal therapies a) Brachytherapy b) Cryotherapy c) High-intensity focused ultrasound (HIFU) d) Laser ablation e) Photodynamic therapy f) Irreversible electroporation 5) Whole gland therapies a) Brachytherapy b) Cryotherapy c) External beam radiation therapy i) three-dimensional conformal radiation therapy ii) intensity-modulated radiation therapy iii) proton beam therapy iv) stereotactic body radiation therapy d) Radical prostatectomy i) open ii) laparoscopic (1) without robotic assistance (2) with robotic assistance 6) Combination of above KQ 2: How do patient characteristics modify comparative effectiveness and harms of CLPC therapies? 1) Age 2) Race/ethnicity 3) Comorbidities 4) Health status KQ 3: How do tumor characteristics modify comparative effectiveness and harms of CLPC therapies? 1) Baseline PSA 2) Gleason score 3) Tumor index scores (e.g., Cancer of the Prostate Risk Assessment Score [CAPRA], D’Amico Risk Classification for Prostate Cancer, etc.) 4) Biomarker Status a) Decipher (Genomic Classifier) b) Oncotype Dx (Genomic Prostate Score) c) Prolaris (Cell Cycle Progression) KQ 4: How do provider/hospital characteristics modify comparative effectiveness of RP compared to other therapies? 1) Geographic region 2) Hospital type 3) Provider volume 4) Institutional volume

Associated Extraction Forms


Associated Studies (each link opens a new tab)

Title Authors Year
External beam radiation therapy with or without low-dose-rate brachytherapy: Analysis of favorable and unfavorable intermediate-risk prostate cancer patients.
Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base. -- Not Found --
Health-related quality of life in active surveillance and radical prostatectomy for low-risk prostate cancer: a prospective observational study (HAROW - Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting). 2018
Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. 2017
Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years. 2017
Curative Radiation Therapy at Time of Progression Under Active Surveillance Compared With Up-front Radical Radiation Therapy for Prostate Cancer. 2018
Radical prostatectomy or watchful waiting in early prostate cancer. 2014
Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up. 2018
Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991. 2016
Relief of Urinary Symptom Burden after Primary Prostate Cancer Treatment. 2017
Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.
Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy. 2015
Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer. 2016
Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results of The Scandinavian Prostate Cancer Group-7. 2016
Patient-reported Functional Outcomes Following Open, Laparoscopic, and Robotic Assisted Radical Prostatectomy Performed by High-volume Surgeons at High-volume Hospitals. 2016
Ten-Year Treatment Outcomes of Radical Prostatectomy Vs External Beam Radiation Therapy Vs Brachytherapy for 1503 Patients With Intermediate-risk Prostate Cancer. 2020
10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. 2016
Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT. 2018
The Treatment of Localized Prostate Cancer in Everyday Practice in Germany. 2016
Community-based Outcomes of Open versus Robot-assisted Radical Prostatectomy. 2018
Patient-Reported Outcomes Through 5 Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer. 2020
Treatment Decision Regret Among Long-Term Survivors of Localized Prostate Cancer: Results From the Prostate Cancer Outcomes Study. 2017
A 25-year Period Analysis of Other-cause Mortality in Localized Prostate Cancer. 2019
Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life. 2016
Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. 2014
Comparison of Patient-reported Outcomes After External Beam Radiation Therapy and Combined External Beam With Low-dose-rate Brachytherapy Boost in Men With Localized Prostate Cancer. 2018
Risk of Small Bowel Obstruction After Robot-Assisted vs Open Radical Prostatectomy. 2016
Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial. 2020
Impact of time to testosterone rebound and comorbidity on the risk of cause-specific mortality in men with unfavorable-risk prostate cancer. 2018
PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer. 2016
Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer.
Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer. 2016
Ten-year Mortality, Disease Progression, and Treatment-related Side Effects in Men with Localised Prostate Cancer from the ProtecT Randomised Controlled Trial According to Treatment Received. 2020
Five-year Outcomes for a Prospective Randomised Controlled Trial Comparing Laparoscopic and Robot-assisted Radical Prostatectomy. 2018
Prostate Cancer Death After Radiotherapy or Radical Prostatectomy: A Nationwide Population-based Observational Study.
ASCENDE-RT: An Analysis of Health-Related Quality of Life for a Randomized Trial Comparing Low-Dose-Rate Brachytherapy Boost With Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer. 2017
ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer. 2017
Erectile Function and Oncologic Outcomes Following Open Retropubic and Robot-assisted Radical Prostatectomy: Results from the LAParoscopic Prostatectomy Robot Open Trial. 2018
Active Surveillance Versus Radical Prostatectomy in Favorable-risk Localized Prostate Cancer. 2019
Pathologic Outcomes in Favorable-risk Prostate Cancer: Comparative Analysis of Men Electing Active Surveillance and Immediate Surgery. 2016
Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy. 2016
Racial Variation in Patient-Reported Outcomes Following Treatment for Localized Prostate Cancer: Results from the CEASAR Study. 2017
Effect of Prostate Cancer Severity on Functional Outcomes After Localized Treatment: Comparative Effectiveness Analysis of Surgery and Radiation Study Results. 2018
Intensity-modulated radiotherapy reduces toxicity with similar biochemical control compared with 3-dimensional conformal radiotherapy for prostate cancer: A randomized clinical trial. 2016
HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer. 2016
Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. 2019
Follow-up of Prostatectomy versus Observation for Early Prostate Cancer. 2017
Significant association of brachytherapy boost with reduced prostate cancer-specific mortality in contemporary patients with localized, unfavorable-risk prostate cancer. -- Not Found --
Lack of Benefit From the Addition of External Beam Radiation Therapy to Brachytherapy for Intermediate- and High-risk Prostate Cancer. 2017
Focal Laser Ablation Versus Radical Prostatectomy for Localized Prostate Cancer: Survival Outcomes From a Matched Cohort. 2019
Brachytherapy improves outcomes in young men (≤60 years) with prostate cancer: A SEER analysis. -- Not Found --
Using a population-based observational cohort study to address difficult comparative effectiveness research questions: the CEASAR study. 2013
Effectiveness of androgen-deprivation therapy and radiotherapy for older men with locally advanced prostate cancer. 2015
Treatment and 5-year survival in patients with nonmetastatic prostate cancer: the Norwegian experience. 2014
Long-term adverse effects after retropubic and robot-assisted radical prostatectomy. Nationwide, population-based study. 2017
Prostate brachytherapy, either alone or in combination with external beam radiation, is associated with longer overall survival in men with favorable pathologic Group 4 (Gleason score 8) prostate cancer. -- Not Found --
The burden of overtreatment: comparison of toxicity between single and combined modality radiation therapy among low risk prostate cancer patients. 2015
Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes. 2015
Primary radiotherapy vs conservative management for localized prostate cancer--a population-based study. 2015
Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database. 2017
Initial results of a randomized phase III trial of high dose image guided radiation with or without androgen deprivation therapy for intermediate-risk prostate cancer. 2019
Survival After Conservative Management Versus External Beam Radiation Therapy in Elderly Patients With Localized Prostate Cancer. 2016
Prostate-Specific Antigen Failure and Risk of Death Within Comorbidity Subgroups Among Men With Unfavorable-Risk Prostate Cancer Treated in a Randomized Trial. 2016
External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens. 2015
Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis. 2015
Initial toxicity, quality-of-life outcomes, and dosimetric impact in a randomized phase 3 trial of hypofractionated versus standard fractionated proton therapy for low-risk prostate cancer. -- Not Found --
Adjuvant versus neoadjuvant androgen deprivation with radiotherapy for prostate cancer: does sequencing matter? 2015

Downloadable Data Content

  • XLSX Project Data