OBSERVATION COST EFFECTIVE FOR MANY PROSTATE CANCER PATIENTS 

For many men with low-risk, localized prostate cancers who are 65 and 75 years of age, observation might be a better option than immediate treatment, and it costs less, according to a new modeling study. Following these men with either active surveillance or watchful waiting provided a better quality-adjusted life expectancy at a lower cost than immediate treatment.

Furthermore, the researchers found that watchful waiting, which relies on observation without monitoring and palliative treatment when symptoms develop, was superior in terms of efficacy and cost to active surveillance, which is more intensive and involves serial prostate-specific antigen (PSA) tests, digital rectal examinations, and biopsies.

Specifically, watchful waiting provided 2 additional months of quality-adjusted life expectancy for 65-year-old men, compared with active surveillance (9.02 vs 8.85 years), at a savings of $15,374 ($24,520 vs $39,894). Watchful waiting also provided 2 additional months for 75-year-old men (6.14 vs 5.98 years), at a savings of $11,746 ($18,302 vs $30,048).

Brachytherapy was the most effective and least expensive initial treatment, according to the study authors, led by Julia Hayes, MD, a medical oncologist in the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts.

Their study appears in the June 18 issue of the Annals of Internal Medicine.

The researchers hope that this study will encourage wider use of observation, including watchful waiting, for men with low-risk disease.

There are no strong numbers on the percentage of men managed with watchful waiting in the United States, said Dr. Hayes. "We can't disentangle active surveillance from watchful waiting in the studies that report treatment patterns, unfortunately," she said in an email to Medscape Medical News.

"I do have patients I manage on watchful waiting, meaning I follow them without invasive surveillance because there is no treatment with curative intent — primarily elderly men with comorbidities," she explained.

"I think observation, in general, is gaining traction in the community," Dr. Hayes added.

However, another expert in the field, whose institution also supports the use of observation for low-risk prostate cancer, believes this modeling study's findings are problematic.

"We believe that active surveillance uptake among low-risk cases is increasing. Both active surveillance and watchful waiting are definitely viable for older men with low-risk disease," said Roman Gulati, MS, from the division of public health sciences at the Fred Hutchison Cancer Research Center in Seattle, Washington.

Gulati, who was not involved with the modeling study, was asked by Medscape Medical News to comment on the strength of this statistically complex evidence.

"Clinicians should recognize that key study assumptions have weak support, particularly the assumption — based on a very uninformative subgroup analysis — that watchful waiting is more effective than radical prostatectomy for low-risk cases," he said in an email.

The subgroup analysis he refers to is from the Prostate Cancer Intervention Versus Observation Trial (PIVOT), which Dr. Hayes and colleagues leaned on heavily for their analysis. The PIVOT investigators found that after a median follow-up was 10 years, men with low-risk prostate cancer derived no benefit from radical prostatectomy, compared with watchful waiting, in all-cause mortality or prostate-cancer-specific mortality, as reported by Medscape Medical News.

However, Gulati said that the prostate cancer mortality data from PIVOT is underpowered, which throws off the conclusions of the modeling study.

"It's possible that the PIVOT point estimate [in the modeling study] is due to chance, since it's based on very few prostate cancer deaths (4 of 148 in the watchful waiting group and 6 of 148 in the radical prostatectomy group)," he explained. Other PIVOT subgroup analyses yielded point estimates that favored radical prostatectomy over watchful waiting, but those were based on a Gleason score below 7 (hazard ratio [HR], 0.68) or, separately, based on a PSA level of 10 ng/mL or less (HR, 0.92) in a larger population of men.

"It seems suspicious that the only PIVOT subgroup comparison with a point estimate that favors watchful waiting over radical prostatectomy forms such an important basis of the main conclusions" of the modeling study, he said.

To their credit, Dr. Hayes and colleagues acknowledge that their study is limited by the subgroup analysis from PIVOT, which has been "criticized for being underpowered."

Gulati also criticized another aspect of the modeling study. "This study does not compare different active surveillance approaches, some of which may be more appealing than others, or provide a basis for arguing in favor of watchful waiting over all active surveillance protocols," he said.

Least and Most Expensive Management

In their modeling study, Dr. Hayes and colleagues performed a decision analysis simulating treatment or observation using data from Medicare schedules and the published literature, including PIVOT.

The team looked at men 65 and 75 years of age with newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 3="" a="" and="" costs.="" disease="" expectancy="" expected="" g="" gleason="" healthcare="" life="" lifetime.="" made="" measures="" nbsp="" outcome="" over="" p="" primary="" projections="" quality-adjusted="" score="" stage="" their="" were="">

The management approaches analyzed were treatment (brachytherapy, intensity-modulated radiation therapy [IMRT], or radical prostatectomy) and observation (active surveillance or watchful waiting).

In the model, the lifetime risk for death from prostate cancer was 4.8% for men on active surveillance, 6.0% for men on watchful waiting, and 8.9% for men treated initially.

Life expectancy was similar for the strategies: 81.6 years for men on active surveillance, 81.4 years for men on watchful waiting, and 81.2 years for men treated initially.

The researchers estimated the lifetime costs of each strategy, which ranged from a low of $18,302 for watchful waiting for 75-year-old men to a high of $48,699 for a 65-year-old men treated with IMRT therapy.

The study was supported by grants from the National Cancer Institute, US Department of Defense, Prostate Cancer Foundation and Blue Shield of California Foundation. Dr. Hayes reports receiving grants from the US Department of Defense and the Prostate Cancer Foundation, and receiving royalties from UpToDate. Some of her coauthors report financial relationships, as detailed in the paper.

Ann Intern Med. 2013;158:853-860. Abstract