Comparing the Effects of Surgery, Radiation Therapy, and Active Surveillance on Men with Localized Prostate Cancer -- The CEASAR Study

This project has results

Abstracts

Public Abstract

Download this abstract: English (pdf) | Español (pdf) | Audio Recording (mp3)

What was the research about?

Prostate cancer occurs most often in men age 50 years and older. Usually, the cancer doesn’t spread beyond the prostate gland. Doctors call this localized prostate cancer. Many men live for a long time after being diagnosed with localized prostate cancer.

The research team looked at three common treatments for localized prostate cancer:

Surgery, called radical prostatectomy, which removes the prostate gland completely
External beam radiation therapy, which focuses tissue-destroying beams of radiation onto the prostate gland
Active surveillance, which includes regular checkups to see if the cancer progresses; checkups usually include blood tests or biopsies, where a small amount of prostate tissue is removed and sent to a lab

The research team wanted to know if there was a difference in the effects for the three treatment choices. Over three years, the team asked the men about their sexual function and urine or bowel problems.

What were the results?

Sexual function. After three years, men who had surgery reported lower sexual function than the men who had radiation or active surveillance. Men who had radiation and those who had active surveillance reported similar sexual function.

Leaking of urine. Men who had surgery reported more leaking of urine than the men who had radiation or active surveillance. Men who had radiation and those who had active surveillance reported similar leaking of urine.

Other urine or bowel problems. The research team asked about pain or reduced stream when passing urine, blood in the urine, and passing urine often. The team also asked about bowel function and hormone function. The only difference was that men who had surgery reported fewer of the urinary problems than men who had active surveillance.

Who was in the study?

The study included 2,550 men from across the United States with localized prostate cancer. All the men started the study within six months of being diagnosed. Of these, 74 percent were white, and 26 percent were other races. The average patient age was 64, and all were younger than 80. Of the surgeries, 76 percent used a laparoscope, a small robotic instrument with a video camera that works through small cuts to the body. Among the men who chose radiation, 45 percent also took medicines to reduce male hormones.

What did the research team do?

The research team used health records to find out which treatment each man received. The men completed a survey when the study began and three years later. The survey asked about sexual function and urine or bowel problems.

A group of 15 prostate cancer survivors helped the research team plan the study; 2 survivors helped conduct the study.

What were the limits of the study?

The study didn’t measure other results that may be important to men with localized prostate cancer, such as overall quality of life, anxiety, satisfaction, and the effect of the cancer on their finances. Also, some results may occur beyond three years.

Future research could follow men for more than three years and might look at other results from treatment such as quality of life or anxiety about cancer.

How can people use the results?

The results could help men with localized prostate cancer and their doctors make treatment choices based on what is most important to the patient.

Professional Abstract

Objective

To compare patient-reported function and symptoms in men with newly diagnosed, localized prostate cancer treated with radical prostatectomy, external beam radiotherapy, or active surveillance

Study Design

Design Elements	Description
Design	Observational: cohort
Population	2,550 men under age 80 with newly diagnosed, localized prostate cancer
Interventions/ Comparators	Radical prostatectomy External beam radiotherapy Active surveillance
Outcomes	Patient-reported sexual function, urinary incontinence, urinary irritative symptoms, bowel symptoms, hormonal function
Timeframe	3-year follow-up for study outcomes

This observational, population-based cohort study compared outcomes for contemporary surgical and radiation techniques and active surveillance for localized prostate cancer. The study outcomes were patient-reported function and symptoms at three-year follow-up, assessed by the 26-item Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire, including sexual function, urinary continence, urinary irritative symptoms, bowel function, and hormonal function.

Researchers enrolled 2,550 men across the United States with localized prostate adenocarcinoma. Of these, 74% were white and 26% were nonwhite. The mean patient age was 64, and all were under age 80. All participants had a patient prostate specific antigen (PSA) level below 50 ng/mL.

Study participants had chosen among three interventions: radical prostatectomy (59.7%), external beam radiotherapy (23.5%), or active surveillance (16.8%). Radical prostatectomy was most commonly performed using robotic-assisted laparoscopy (76%). External beam radiotherapy was primarily delivered using an intensity-modulated approach (81%) and supplemented with androgen deprivation therapy in 45% of the men. Active surveillance included serial PSA measurements and prostate biopsies as needed.

Participants completed the EPIC-26 at enrollment and six months, one year, and three years later.

Two prostate cancer survivors were active members of the research team. A patient advisory council of 15 survivors also provided input on the aims and conduct of the study.

Results

Results are for follow-up at three years.

Sexual function. Men who had surgery scored lower on sexual function than those who had radiotherapy (p<0.001) or active surveillance (p<0.001); the differences were statistically and clinically significant. Men who had radiotherapy or active surveillance scored similarly on sexual function.

Urinary continence. Men who had surgery scored lower on urinary continence than those choosing radiotherapy (p<0.001) or active surveillance (p<0.001); the differences were statistically and clinically significant. Men who had radiotherapy and those who had active surveillance scored similarly on urinary continence.

Urinary irritative symptoms. Men who had surgery reported less problems with urinary irritative symptoms (dysuria, hematuria, reduced stream, increased frequency) than those who had active surveillance (p<0.001); the difference was statistically and clinically significant. Men who had surgery did better than those who had radiotherapy, and those with radiotherapy did better than those with active surveillance; the differences were statistically but not clinically significant.

Other domains. Bowel function was better after surgery than after radiotherapy; the difference was statistically but not clinically significant. Hormonal function was not statistically or clinically significantly different among groups.

Limitations

The study did not measure other outcomes relevant to localized prostate cancer, such as long-term functional outcomes and oncologic endpoints, overall quality of life, anxiety, satisfaction, and financial impacts. Also, some favorable or adverse outcomes may present beyond three years; the number and severity of such outcomes may differ by treatment.

Conclusions and Relevance

At three-year follow-up, men who had radical prostatectomy saw lower sexual function and more urinary incontinence than men who had radiotherapy or active surveillance. However, men who had surgery had less problems with irritative symptoms than men who chose active surveillance. Researchers observed no other clinically significant differences between treatments.

These results can help inform treatment decisions for men with newly diagnosed, localized prostate cancer. However, other factors to consider include the tumor grade and PSA level.

Future Research Needs

Future research could have longer follow-up periods and might study other outcomes such as overall quality of life, anxiety, and financial impacts.

This project's final research report is expected to be available by June 2019.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

The reviewers, noting that the exclusion of 7 percent of the sample, or 200 patients, from analyses because researchers had no post-baseline data, asked whether these patients differed in any way from the included patients. The investigators replied that the two groups differed on race and on one quality-of-life outcome at baseline. While the researchers added this limitation to the report, they said that they did not believe this difference changed their conclusions.
The reviewers expressed concern that the analyses did not include a correction for multiple comparisons and that some apparently statistically significant differences might be due to chance. The researchers responded that they identified all of their hypotheses a priori and an adjustment for multiple comparisons was not appropriate when testing a pre-specified hypothesis.
The reviewers requested additional information on how the researchers accounted for potential clustering by site in the analyses. Clustering by site can lead to unmeasured between-patient correlations that could bias the aggregate results. The researchers explained that they had accounted for site as a covariate in their statistical models but said that they did not test for a site by treatment interaction. The researchers added as a study limitation a comment about the potential for bias due to clustering by site.

Conflict of Interest Disclosures

View the COI disclosure form.

Related PCORI Dissemination and Implementation Project

Using PCORI Data to Drive Better Decisional Quality for Men with Localized Prostate Cancer

Journal Articles

JAMA

Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years

The Journal of Urology

The Comparative Harms of Open and Robotic Prostatectomy in Population Based Samples

International Journal of Radiation Oncology, Biology, Physics

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

The Journal of Urology

The Effect of Nerve Sparing Status on Sexual and Urinary Function: 3-Year Results from the CEASAR Study

European Urology

Racial Variation in Patient-Reported Outcomes Following Treatment for Localized Prostate Cancer: Results from the CEASAR Study

Medical Care

Impact of Adherence to Quality Measures for Localized Prostate Cancer on Patient-reported Health-related Quality of Life Outcomes, Patient Satisfaction, and Treatment-related Complications

More on this Project

Evidence for Decisions

Early-Stage and Localized Prostate Cancer
Early-stage prostate cancer can be treated in different ways. Two recent PCORI-funded research studies provide new information on the effects of treatments and can help patients navigate their treatment decisions.

Continuing Medical Education/Continuing Education Activity

Contemporary Treatment Options for Prostate Cancer
This online activity, comprised of two didactic presentations and a panel discussion, highlighted findings from this and another PCORI-funded project about contemporary treatment options for localized prostate cancer. The activity was designed to help health care professionals and their patients explore and compare the benefits, harms, and risks of treatments and choose an option that best fits a patient’s preferences and priorities.

PCORI Stories

Helping Men Decide on Prostate Cancer Treatment
An update to a feature story on the difficult decisions newly diagnosed prostate cancer patients have to make and the men who join Vanderbilt University researchers to personalize information on treatment outcomes. Problems are more likely three years after surgery than after radiation or surveillance, the study finds.

Videos

Helping Men Make Better Decisions about Prostate Cancer
David Penson, MD, MPH, of Vanderbilt University and the principal investigator of the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) prostate cancer study describes how the study differs from other research.

Project Details

Principal Investigator

David Penson, MD, MPH

Project Status

Completed; PCORI Public and Professional Abstracts Posted

Project Title

Generating Critical Patient-Centered Information for Decision Making in Localized Prostate Cancer

Board Approval Date

May 2013

Project End Date

September 2018

Organization

Vanderbilt University

Year Awarded

2013

State

Tennessee

Year Completed

2018

Project Type

Research Project

Funding Announcement

Assessment of Prevention, Diagnosis, and Treatment Options

Conditions

Cancer

Prostate Cancer

Project Budget

$2,007,390

Study Registration Information

HSRP20143300

NCT01326286

Page Last Updated:

April 18, 2019