Clinical Question

What is the best approach to the management of localized prostate cancer?

Bottom Line

This landmark study compared active surveillance with radical prostatectomy or radiation therapy for patients with T1c or T2 prostate cancer. The benefits of active surveillance include avoiding radical therapy in one-half of the patients, with no effect on disease-specific survival or all-cause survival. The potential harms include a greater risk of metastatic disease (three additional cases per 1,000 person-years, corresponding to three additional cases for 100 men followed up for 10 years) and a greater likelihood of clinical progression. An accompanying study (N Engl J Med. 2016;375(15):1425–1437) discusses the effects on quality of life and complications of treatment. (Level of Evidence = 1b)

Synopsis

Clinically localized prostate cancer is defined as stage T1c or T2, and is confined to the prostate gland. In this study, 82,429 British men 50 to 69 years of age had a prostate-specific antigen (PSA) test. Of those, 2,664 had grade T1c or T2 cancer, and 1,643 agreed to be randomized to one of three groups: radical prostatectomy, radiotherapy, or a program of active surveillance. Active surveillance consisted of frequent PSA tests (every three months in the first year and every six to 12 months after that), with a rise of 50% or more triggering an evaluation for possible biopsy and treatment, if indicated. Approximately 80% of men assigned to surgery or radiotherapy received the assigned treatment during the first year following randomization.

In the active surveillance group, there was a steady increase in the percentage of men who received radiotherapy, prostatectomy, or another treatment with curative intent, from 20% at year 2, to 40% at year 5, to slightly more than 50% at year 10. There was no difference between groups in mortality due to prostate cancer, prostate cancer–specific survival at five or 10 years, or all-cause mortality. However, there was a greater likelihood of developing metastatic disease in the active surveillance group, with approximately three more metastatic cancers detected per 1,000 person-years than in the surgery or radiotherapy groups (P = .004). Clinical progression (defined as progression to T3 or T4 disease, urinary or rectal complications, or the use of androgen deprivation therapy) was also more common in the active surveillance group, with approximately 13 additional patients progressing per 1,000 person-years. Stratification of patients by age, PSA result, Gleason score, or stage at diagnosis did not affect the results.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (specialty)

Reference: HamdyFCDonovanJLLaneJAet alProtecT Study Group10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med2016;375(15):1415–1424.