Prostate Cancer Adverse Events Persist 5 to 10 Years After Treatment

Megan Brooks

July 05, 2012

July 5, 2012 — Clinically significant sexual and urinary problems related to prostate cancer treatment persist for up to a decade after treatment, according to an analysis of data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial, published online June 25 in the Journal of Clinical Oncology.

Average sexual and urinary dysfunction is still very poor 5 to 10 years after diagnosis.

"Although side effects do remit for some men within a year following treatment, average sexual and urinary dysfunction is still very poor 5 to 10 years after diagnosis," first author Kathryn L. Taylor, PhD, from the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, DC, told Medscape Medical News.

"Therefore, providers need to continue managing these side effects long after the diagnosis and treatment have passed," Dr. Taylor said.

The treatment-related impairments are an argument for employing active surveillance, she noted.

"For men with low-risk prostate cancer (i.e., cancer that is unlikely to progress based on tumor characteristics and PSA [prostate-specific antigen] levels), providers should discuss the possibility of active surveillance with their patients, which leaves open the possibility of later treatment if needed but reduces the likelihood of having to endure treatment side effects if treatment can be avoided," Dr. Taylor explained.

However, an expert not involved in the study said the findings are expected and that the study had a major shortcoming.

The conclusions are very unsurprising.

"The conclusions are very unsurprising," said Stephen Freedland, MD, from Duke University Medical Center in Durham, North Carolina.

In an interview with Medscape Medical News, Dr. Freedland said that although men can have problems with urinary and sexual function related to aging, "treatment for cancer adds above and beyond to urinary and sexual problems."

In addition, the study neglected an important measure in these men, he suggested. The authors "did not measure global quality of life; to me, that's the key thing — how you are doing in your overall health and life," said Dr. Freedland, who is editor-in-chief of Prostate Cancer and Prostatic Diseases.

Still, this study has a "unique design and answers a question that maybe was not completely answered," he said, referring to findings about specific adverse events.

Cancer Survivors Have Worse Function

The degree to which routine PSA testing reduces prostate cancer mortality remains a topic of debate. As previously reported by Medscape Medical News, results from the European Randomized Study of Screening for Prostate Cancer showed a decrease of about 20% in prostate-cancer-related mortality; however, the American PLCO trial found no impact of screening on mortality. A recent essay by a team of international authors asserted that the "best" screening trials show a mortality benefit of 20% to 44%, and that the PLCO trial was deeply flawed.

Whether treating early-stage prostate cancer leads to survival differences for a screened population also remains unclear; this uncertainty magnifies the importance of adverse events related to screening and treatment, the authors note.

"When the survival benefit is uncertain, patient-reported outcomes such as disease-specific function are critical for making informed treatment decisions and for understanding whether the quality of years living with prostate cancer justifies screening," Dr. Taylor and colleagues report.

Using PLCO trial data, they assessed long-term disease-specific functioning in 529 screened prostate cancer survivors and 514 screened noncancer control subjects matched for race, screening center, year of enrollment, and trial group.

They found that survivors had significantly worse sexual and urinary function than the control subjects (P < .001), suggesting that these long-term problems were due to prostate cancer and its treatment rather than solely to comorbidities or aging. "These results corroborate those of previous studies that have included noncancer controls and revealed greater symptomatology among prostate cancer survivors," they note.

Cancer-Detection Method Makes No Difference

The team also compared the impact of regular screening with usual care on disease-specific functioning among survivors. They found that the route to diagnosis (regular screening vs usual care) was not associated with disease-specific functioning (P < .31 for all outcomes). This finding, they say, suggests that survivors with screen-detected prostate cancer have a rate of long-term adverse effects similar to survivors of prostate cancer detected with usual care.

The United States Preventive Services Task Force (USPSTF) recently recommended against routine PSA-based prostate cancer screening for healthy men, regardless of age.

However, Dr. Taylor told Medscape Medical News that her team's results "don't address the USPSTF recommendations. We did not assess mortality differences in our study, as this was a substudy of the larger PLCO trial, which did report mortality outcomes."

Treatment Modality Matters

Dr. Taylor and colleagues also examined the impact of treatment modality on long-term disease-specific functioning, and they found clear differences. The 110 patients who received radiation therapy reported better sexual (P < .05) and urinary (P < .001) functioning, but poorer bowel outcomes (P < .05), than the 201 patients who underwent radical prostatectomy.

The 207 survivors who received treatment combinations, including androgen-deprivation therapy, reported significantly worse hormone-related symptoms than those who underwent radical prostatectomy (P < .05).

"The greater long-term urinary and sexual dysfunctions among survivors treated by surgery compared with radiation are particularly important...when making treatment decisions," Dr. Taylor and colleagues report.

They point out that the differences in adverse effects between treatment modalities persist 5 to 10 years after diagnosis. "However, both surgery and radiation resulted in poor sexual functioning, which [suggests] that providers need to be prepared to manage these chronic, long-term adverse effects regardless of the treatment modality."

They note that more than 95% of men in each treatment group reported having at least some sexual dysfunction, and approximately 50% of men in each treatment group reported having at least some urinary and bowel dysfunction.

The study limitations include a lack of pretreatment information on health-related quality of life and the cross-sectional design. In addition, the opportunistic screening that occurred in the usual-care group could have limited the ability to detect differences in the trial groups, they point out.

They also note that 40% of participants in the usual-care group were screened in the first year and 52% were screened in the sixth year, meaning that the majority of prostate cancer survivors were diagnosed with early-stage disease, which might have resulted in the absence of differences in the 2 trial groups.

The authors report they did not have a large enough sample to compare the impact of brachytherapy with that of external-beam radiation therapy. They also did not use a validated index to assess comorbidities.

Despite these limitations, they say the results of this analysis provide "essential information" for patients and clinicians making screening and treatment decisions by documenting differences in long-term urinary and sexual dysfunction after radical prostatectomy and radiation therapy.

The study was supported by the Midwest Division of the American Cancer Society. The authors have disclosed no relevant financial relationships. Dr. Freedland reports being a consultant/speaker for Janssen and Amgen, a consultant for Dendreon, and a speaker for AstraZeneca.

J Clin Oncol. Published online June 25, 2012. Abstract

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