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Ten years after a diagnosis of localized prostate cancer, men had a similar risk of dying of the disease regardless of whether they chose surgery, radiation therapy (RT), or active monitoring (AM; also called active surveillance or AS), an exploratory analysis of a multicenter trial showed.

Among 997 patients who chose their own treatment approach, 10-year prostate cancer-specific mortality was 1.85% with AS, 0.67% with surgery, and 0.73% with RT, a difference that did not achieve statistical significance (P=0.08). An exploratory analysis that included treatment-choice cohorts as well as 1,637 randomized patients showed a stronger trend for lower prostate cancer mortality with active treatment (P=0.003).

Men in the AS group also had higher rates of metastasis and disease progression, whereas surgery and RT were associated with more sexual, urinary, and bowel dysfunction, as reported in .

Collectively, the results "confirmed that surgery and RT reduce metastasis and progression compared with AM, but impact sexual, urinary and bowel functioning," stated David E. Neal, MD, of the University of Oxford in England, and colleagues.

In a patient-directed summary, they emphasized the generally favorable outlook for localized prostate cancer: "More than 95 out of every 100 men with low or intermediate-risk localized prostate cancer do not die of prostate cancer within 10 years, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy."

Has Pendulum Swung Too Far?

The results are consistent with those of a that focused on outcomes in the randomized cohort and showed an overall prostate cancer-specific survival rate of 98.8% at 10 years in the study. The updated analysis showed more separation between the AS and upfront-treatment groups, and the analysis of the men who declined randomization and chose their own treatment showed an even greater survival difference in favor of definitive treatment.

The new data prompted authors of an to question whether "the pendulum has swung too far towards surveillance."

"While we note that such comparisons of PCa [prostate cancer] mortality should be considered exploratory, as they were not in the original randomization protocol, these data still represent relatively high-quality evidence and underscore the small but increased risk of PCa mortality for patients on AM compared to treatment," wrote Vidit Sharma, MD, and R. Jeffrey Karnes, MD, both of the Mayo Clinic in Rochester, Minnesota. "This necessitates a thorough discussion of the risks of AM, particularly for patients with intermediate- or high-risk PCa."

Despite limitations of the study -- relatively "loose" monitoring in the AS arm and potential for selection bias in the selected-treatment arm -- the data provide reason to reconsider the role of AS in men with favorable intermediate-risk PCa, they added.

"In our decision analytic of the original ProtecT data, initial treatment was the preferred option for patients with more than a 2.4% 10-year risk of metastasis on active surveillance. On this basis, active surveillance is probably the right choice for most men with low-risk PCa and select men with favorable intermediate-risk PCa. However, incorporation of the newfound PCa mortality and metastasis estimates into such models would cause surveillance to be suitable for even fewer men with intermediate-risk PCa."

ProtecT Objectives, Results

The primary objective of ProtecT was prostate cancer-specific mortality after a median follow-up of 10 years in the randomized portion of the study population. Secondary outcomes included rates of disease progression and distant metastasis and all-cause mortality. Overall, 17 patients in the randomized cohort died of prostate cancer, as did 14 in the treatment-choice cohort.

In the updated analysis, Neal and colleagues analyzed outcomes by actual treatment received, including both the randomized and treatment-choice cohorts. In the treatment-choice group, 507 (51%) men opted for AS, 262 chose radical prostatectomy, and 189 (19%) chose RT. For the exploratory analyses, investigators combined men treated with surgery or RT.

In the randomized cohort, the combined active-treatment group had a 66% reduction in the hazard for prostate cancer death as compared with the AS group (95% CI 0.13-0.94). In the treatment-choice group, upfront definitive therapy was associated with a 73% reduction in the hazard versus AS (95% CI 0.08-0.91).

A pooled analysis of the randomized and treatment-choice data yielded a 69% reduction in the hazard for prostate cancer death in favor of active treatment (95% CI 0.14-0.67, P=0.003). Because of the relatively small number of prostate cancer deaths, the difference represented a modest absolute risk reduction, the authors acknowledged.

Analysis of the treatment-choice group showed the rate of distant metastasis in the AS patients (5.6%) was twice that of the patients who opted for surgery (2.4%) or RT (2.7%). Disease progression occurred more than three times as often with AS (20.35%) as with surgery (5.87%) or RT (6.62%).

As expected, treatment-related side effects occurred more often in men who chose radical therapy. Sexual dysfunction at 6 months was reported by 95% after radical prostatectomy and urinary incontinence by 55%. Among men who chose RT, 88% reported sexual dysfunction at 6 months and 5% reported bowel dysfunction.

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