Harms From Prostate Cancer Tx Persist at 5 Years

Pam Harrison

January 22, 2020

Changes in urinary, bowel, and sexual function associated with different treatment options for prostate cancer decline over time, but some of these adverse effects persist and are still bothersome 5 years later, an updated analysis shows.

"Five-year disease-specific survival for localized prostate cancer approaches 100%," note the authors.

"[D]ifferences in urinary, bowel, sexual, and hormonal function are the most salient outcomes during this period and may drive patient treatment selection," they suggest.

The findings come from the Comparative Effectiveness Analysis of Surgery and Radiation (CAESAR) study and were published online January 14 in JAMA.

They show that men who opted for surgery experienced more long-term adverse effects, including incontinence and worse sexual function, than men who opted for other treatment approaches, which included external-beam radiotherapy (EBRT), either with or without androgen deprivation therapy (ADT), low-dose-rate (LDR) brachytherapy, and active surveillance.

"In this cohort study, contemporary management strategies for localized prostate cancer were associated with distinct adverse effect profiles," comment the authors, led by Karen Hoffman, MD, MPH, the University of Texas MD Anderson Cancer Center, Houston.

"These estimates of the long-term bowel, bladder and sexual function after localized prostate cancer treatment may clarify expectations and enable men to make informed choices about care," they conclude.

Comparing Harms From Various Treatment Approaches

The CAESAR study was designed to inform men of the comparative harms of the different strategies used to treat localized prostate cancer, the authors explain.

Men were grouped into those with favorable-risk or unfavorable-risk disease. Surveys were completed at baseline and at 6 months, as well as 1, 3, and 5 years after enrollment.

Of 1386 men with favorable-risk disease, 49% underwent nerve-sparing prostatectomy; 26% were treated with active surveillance; 19% received EBRT without ADT; and 6% underwent LDR brachytherapy, the researchers report.

Patient-reported outcomes were evaluated using the Expanded Prostate Index Composite questionnaire.

"There was no statistically significant difference in prostate cancer survival over 5 years, with only 1 prostate cancer–related death in the favorable-risk group and 8 in the unfavorable-risk group," the authors report.

However, at 5 years, more men who underwent prostatectomy (35%) reported having a "moderate" or a "big" problem with sexual function than the men who underwent active surveillance (24%) (P < .001). In addition, 61% of the patients treated with prostatectomy reported having erections that were insufficient for intercourse, compared to 57% of men who underwent active surveillance (P < .001).

On the other hand, approximately half of men who were treated with either nerve-sparing prostatectomy, EBRT, or LDR brachytherapy and who had erections sufficient enough for intercourse at baseline either retained or regained erections sufficient enough for intercourse at 5 years.

This was also true for 66% of the men who underwent active surveillance, the researchers note.

Bladder and Bowel Function

"A clinically meaningful decline in urinary incontinence function...was shown in men who underwent nerve-sparing prostatectomy," the team reports, although there was a subsequent, if limited, improvement in their incontinence by year 5.

In contrast, a clinically meaningful improvement in urinary irritative function (eg, frequency, urgency, urge incontinence, nocturia) was reported by men who underwent prostatectomy at the same time point.

A decline in urinary irritative function was initially observed in men treated with LDR brachytherapy, but symptoms resolved to baseline levels at 3 and 5 years post treatment.

Interestingly, "there were no clinically meaningful urinary function differences between participants who underwent EBRT and active surveillance at any time point," the researchers report.

Again at 5 years, no statistically significant differences in moderate or big problems with urinary function, urinary frequency, or burning on urination were observed across treatment groups, although rates of urinary leakage were slightly higher among men treated with prostatectomy than those who underwent active surveillance (P = .04).

Bowel function worsened during the first year for men treated with LDR brachytherapy compared to those treated with active surveillance or prostatectomy (P < .001 for both comparisons).

However, at no time point were there any clinically meaningful differences in bowel function between the EBRT, prostatectomy, or active surveillance groups, the investigators point out.

Unfavorable-Risk Disease

Of the 619 men who had unfavorable-risk disease, 65% were treated with prostatectomy, and 35% underwent EBRT delivered with ADT.

"EBRT with ADT was associated with statistically significantly better sexual function through 5 years than prostatectomy," the researchers report. Clinically meaningful differences between the two groups were observed 6 months post treatment (P < .001).

Similarly, men treated with EBRT plus ADT had significantly better continence function than men treated with surgery. This difference was clinically meaningful at all time points (P < .001 at 5 years).

On the other hand, EBRT plus ADT led to clinically meaningful worse bowel function compared with prostatectomy during the first year after treatment (P < .001) ― a difference that had resolved by year 5.

Predictably, men who underwent EBRT plus ADT experienced a clinically meaningful decline in hormonal function in the short term, but hormonal function improved to baseline levels at 5 years.

In contrast, no clinically meaningful differences in hormone function were observed between any of the treatment groups at study endpoint.

The study was supported by the Agency for Healthcare Research and Quality, the Patient-Centered Outcomes Research Institute, and the National Cancer Institute. Hoffman has disclosed no relevant financial relationships. Two coauthors received personal fees from industry.

JAMA. Published online January 14, 2020. Abstract

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