Fifteen years after being treated with radical prostatectomy or external-beam radiation for localized prostate cancer, “the prevalence of erectile dysfunction was nearly universal,” among men enrolled in a long-term functional outcomes analysis of the Prostate Cancer Outcomes Study (PCOS). There were no significant relative differences in the odds of urinary incontinence or bowel urgency between men treated with prostatectomy or radiotherapy. “Considering the often long duration of survival after treatment for prostate cancer, these data may be used to counsel men considering treatment for localized disease,” the study investigators concluded.

The study was published in The NewEngland Journal of Medicine¹ and reported by the medical and consumer press. The newspaper The Tennessean quoted senior author David F.
Penson, MD, MPH, as saying that both surgery and radiation “cause a whole heck of a lot of side effects.” In an interview with NBC News, Dr. Penson said, “So many of these men have low-risk disease that probably doesn’t need to be treated.” Dr. Penson is the Director of the Center for Surgical Quality and Outcomes Research, Professor of Urologic Surgery, and Ingram Professor of Cancer Research at Vanderbilt University Medical Center in Nashville.

Dr. Penson expanded on these remarks in an interview with The ASCO Post. While men diagnosed with localized prostate cancer generally are aware of the possible side effects of treatment, “I don’t think they appreciate the degree to which it occurs,” Dr. Penson said. “They are told that it is a possibility, but I don’t think they really appreciate just how real the possibility is.” He said that the results of the study can help men “get the complete picture” about the long-term effects of treatment for localized prostate cancer and decide what is best for them.

Disease-specific Functional Outcomes

The PCOS study involved 3,533 men diagnosed with localized prostate cancer in 1994 or 1995. The current analysis was limited to 1,655 men diagnosed between the ages of 55 and 74 and whose primary treatment was either prostatectomy (1,164 men) or external-beam radiation (491 men). In addition to baseline assessments, the men completed self-administered surveys containing items on clinical outcomes and disease-specific health-related quality of life at 2, 5, and 15 years after diagnosis.

According to the study report, “Men in the prostatectomy group were significantly more likely than those in the radiotherapy group to report having erections insufficient for intercourse at 2 years” (78.8% vs 60.8%) and 5 years (75.7% vs 71.9%).

Preserving sexual function for 2 to 5 more years may be a factor in opting for radiotherapy. “There is no denying the fact that there are men who in their late 60s may want to maintain that sexual function for 2 or 3 years. Conversely, there may be young men who, for whatever reason, whether it is cancer control or another reason, choose to sacrifice that upfront sexual function,” Dr. Penson stated.

“At 15 years, the prevalence of erectile dysfunction was nearly universal, affecting 87.0% of men in the prostatectomy group and 93.9% of those in the radiotherapy group. Nonetheless, only 43.5% of men in the prostatectomy group and 37.7% of those in the radiotherapy group reported being bothered with respect to sexual symptoms. The possible reasons for the second finding include declining sexual interest with age, acceptance of sexual dysfunction over time, or both,” the report continued.

Patients who had prostatectomy were more likely to have urinary incontinence than those who had radiotherapy at 2 years (9.6% vs 3.2%) and 5 years (13.4% vs 4.4%). “However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years,” the investigators reported. “Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (13.6% vs 34%) and 5 years (16.3% vs 31.3%), again with no significant between-group difference in the odds of bowel urgency at 15 years,” they added.

Two Major Messages

“If you look at the results, you see that initially sexual functioning is much worse after surgery, but by about 5 years, things are evening out, certainly by 15 years. For urinary continence, it is worse for surgery. For bowel dysfunction, it is worse with radiation,” Dr. Penson summarized. “I hope that patients and providers take away two points from this.”

The first point is that treatment for localized prostate cancer “is a personalized decision,” Dr. Penson stressed. “What works for one patient may not work best for another. For some patients, 2 years’ loss of sexual functioning isn’t going to be acceptable.”

The second point is that patients who have low-risk disease should perhaps “pause and think, ‘Maybe I should try active surveillance, because I may be able to avoid these complications altogether,’” Dr. Penson continued.

“I recognize that every man with prostate cancer has to be treated differently because this is a preference-sensitive decision. I look at these data and I say to myself, ‘If I were newly diagnosed with localized prostate cancer and it was a low-risk tumor, given the fact that the risk of having problems with surgery or radiation are high, maybe I should be thinking about active surveillance,’” Dr. Penson said. “Maybe these data will make a few men think a little more carefully about that option.”

Active Surveillance vs Watchful Waiting

Active surveillance “is a reasonable option,” Dr. Penson said. “We know from the trials that have come out recently, specifically the Prostate Cancer Intervention Versus Observation Trial (PIVOT),² that in low-risk patients and older patients, there is no difference in outcomes between surgery and watchful waiting, which is actually somewhat different than active surveillance,” Dr. Penson noted. “At this point, we can accept active surveillance as a standard of care, not the standard of care, in low-risk patients. That difference is a key point,” he stressed.

“Watchful waiting is the old version of conservative management,” Dr. Penson explained. “We would watch and only make an intervention if patients were symptomatic or if they suddenly changed their status. With active surveillance, we are actively following patients, repeating prostate-specific antigen (PSA) measurements, repeating biopsies, and depending on which protocol you accept, there are thresholds for intervention.” Those thresholds could include a change seen on a repeat biopsy or a rapid rise in PSA and would signal a “need to aggressively intervene with surgery or radiation,” he added.

Patients need to understand the difference between watchful waiting and active surveillance and know that if they choose not to have treatment with surgery or radiation, they can have active surveillance instead. “That is a key point because patients may interpret watchful waiting as ‘watching and waiting for me to drop dead,’ whereas active surveillance is an active follow-up protocol. Active surveillance ensures that if there are any signs that the tumor is not clinically indolent—that it is actually more aggressive—we will make an intervention in a timely manner and hopefully in such a way that it will have the same outcome as if the patient were treated earlier.”

Effects of Normal Aging

The report notes that “regardless of treatment, patients had significant declines in sexual and urinary function over the duration of the study, and the causes of these declines probably include both advancing age and additional cancer treatments.” Dr. Penson explained that “additional cancer treatments” referred only to additional treatments for prostate cancer. “If a man has a recurrence, regardless of whether he had surgery or radiation, the most common form of treatment is going to be hormonal treatment, which is hellish on sexual function,” he said.

The authors acknowledged that “the precise contribution of prostate cancer treatment to age-dependent changes in urinary, sexual, and bowel function remains unknown, given the absence of an untreated, age-matched control cohort.”

Dr. Penson cited one study, led by another PCOS investigator, Richard M. Hoffman, MD, MPH, Professor in the Department of Internal Medicine at the University of New Mexico Cancer Center in Albuquerque, and published in Cancer,³ that compared changes in health-related quality of life between men diagnosed with localized prostate cancer with a cohort of age-matched controls identified using data files from the New Mexico Motor Vehicles Department and the Centers for Medicare and Medicaid Services. Those investigators concluded, “Prostate carcinoma treatment led to significant 5-year declines in urinary and sexual function that far exceeded age-related changes in controls. Bowel function and general [health-related quality of life] were not affected by cancer status.”

Incrementally Better Outcomes

Patients enrolled in PCOS in 1994 and 1995 and some physicians have remarked to Dr. Penson that prostate cancer treatment has improved since then. “Urologists will say, ‘Now we are better with the surgery and we have robotics surgery,’ and radiologists will say, ‘Now we have intensity-modulated radiation therapy and our outcomes are better,’ and I acknowledge that,” Dr. Penson said.

“I think the outcomes are better. But I don’t think they are exponentially better. I think they are incrementally better and I think that it is almost a cop-out to say, ‘We’re not going to pay any attention to these data because we are so much better now.’” ■

Disclosure: Dr. Penson received research grants via his institution from NIH/NCI for the Prostate Cancer Outcomes Study.

References

1. Resnick MJ, Koyama T, Fan KH, et al: Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 368:436-445, 2013.

2. Wilt TJ, Brawer MK, Jones KM, et al: Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 367:203-213, 2012.

3. Hoffman RM, Gilliland FD, Penson DF, et al: Cross-sectional and longitudinal comparisons of health-related quality of life between patients with prostate carcinoma and matched controls. Cancer 101:2011-2019, 2004.