Active monitoring has similar 10-year mortality outcomes as prostatectomy and radiotherapy in men aged 50-69 years with newly diagnosed localized prostate cancer

EBM Focus - Volume 11, Issue 38

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Reference - Prostate Testing for Cancer and Treatment (ProtecT) trial (N Engl J Med 2016 early online) (level 1 [likely reliable] evidence)

  • It is unclear how to best manage newly diagnosed localized prostate cancer first identified by prostate-specific antigen (PSA) screening.
  • The recent ProtecT trial randomized 1,643 men (98% white, aged 50-69 years) with newly diagnosed localized prostate cancer detected by PSA screening to one of three groups: active monitoring versus radical prostatectomy versus radiotherapy, and followed them for a median of 10 years.
  • Cancer-specific and all-cause mortality were similar among the three groups. Prostatectomy and radiotherapy decreased rates of clinical progression, including metastatic disease, compared to active monitoring. However, treatment-related complications are significant, with prostatectomy, in particular, having a sizable and lasting effect on sexual and urinary function.

Prostate cancer has a lifetime risk in the United States of about 15% (CA Cancer J Clin 2014 Jan-Feb;64(1):9), but localized prostate cancer identified by PSA screening generally has a slow progression. It is unclear how to best weigh the possible beneficial effects of prostatectomy or radiotherapy against their complications. The recent National Comprehensive Cancer Network (NCCN) guidelines recommend active surveillance for many men with low-risk prostate cancer, but this recommendation is based on lower-level evidence, albeit with uniform consensus (NCCN website).

The recent ProtecT trial, conducted in the United Kingdom, randomized 1,643 men (98% white, aged 50-69 years) with localized prostate cancer diagnosed after PSA screening to active monitoring versus radical prostatectomy versus radiotherapy (with neoadjuvant androgen deprivation therapy), and followed them for a median of 10 years with regular PSA monitoring. The diagnosed cancers were mostly low-risk: 76% had stage T1c, 77% had a Gleason score = 6, and 90% had PSA levels < 10 ng/mL. Patients in the active monitoring group with a 50% or greater increase in the PSA level over one year during follow-up were managed at physician’s discretion (54% eventually had treatment).

Death due to prostate cancer occurred in 1%, and death of any cause occurred in 10% of the entire cohort. Incidences of both outcomes were not significantly different among groups. However, incidence of any clinical progression was greater with active monitoring (22.9 per 1,000 person-years vs. 8.9 with prostatectomy vs. 9 with radiotherapy, p < 0.001 for difference across groups), as was incidence of metastatic disease (6.3 per 1,000 person-years vs. 2.4 vs. 3, p = 0.004 for difference across groups). Patient-reported outcomes over 72 months post-randomization (reported in a companion article) showed significant treatment-related complications in sexual function, as well as bladder and bowel continence. Men allocated to treatment groups had a decreased likelihood of preserved sexual function shortly after randomization: erection was firm enough for intercourse at 6 months in 51.6% with active monitoring, but in only 12% with prostatectomy and 22.2% with radiotherapy. At 72 months, rates were similar between active monitoring (29.6%) and radiotherapy (27.4%), and both were superior to prostatectomy (16.5%). Rates of complete urinary continence at 6 months were 61% with active monitoring, 29% with prostatectomy, and 61.8% with radiotherapy, and decreased or remained low over time to 49.9%, 31.3%, and 50.8% at 72 months. Bowel dysfunction was mostly infrequent and mild, but generally worse with radiotherapy. Interpretation of these complication rates is limited, however, as statistical tests at specific time points were not reported.

Although allocation to treatment after localized prostate cancer diagnosis did not decrease 10-year mortality compared to active monitoring in this trial, the decreased risk of disease progression raises the possibility that a longer follow-up may reveal a benefit. Only 2% of the men were non-white, which limits the generalization of the findings. Decreased disease progression must be balanced with treatment-related complications, particularly with prostatectomy, when considering whether to treat newly diagnosed PSA-detected localized prostate cancer.

For more information, see the Management of localized or locally advanced prostate cancer topic in DynaMed Plus. DynaMed users click here.