Clinical Question

What are the benefits and harms of different approaches to the treatment of screen-detected prostate cancer?

Bottom Line

Active surveillance provides a balance of benefits and harms. After 15 years, for every 100 participants, 40 can avoid the need for surgery with no increase in the risk of death, although three to four more develop metastatic disease than in the groups treated initially with surgery or radiation. (Level of Evidence = 1b)

Synopsis

The ProtecT study group conducted a randomized controlled trial in the United Kingdom that, with its initial publication five years ago, provided the best information available on the benefits and harms of surgery, radiation, and active surveillance for men with screen-detected prostate cancer. Of the 2,664 men with localized prostate cancer detected by screening between 1999 and 2009, a remarkable 1,643 agreed to be randomized to prostatectomy, radiotherapy, or active surveillance. With active surveillance, any patient or physician concern or an increase of at least 50% in prostate-specific antigen level prompted a review, further testing as appropriate, and consideration for therapy. The study reported the outcomes for a median of 15 years following enrollment.

The primary and secondary outcomes were reported per 1,000 person-years, which is difficult to interpret clinically. It can be reframed as 100 patients followed for 10 years, or 67 patients followed for 15 years. The primary outcome of prostate cancer–specific mortality was uncommon, with no significant difference among the groups, ranging from 1.5 to 2.2 deaths per 1,000 person-years (or per 100 men followed for 10 years). There was no significant difference in all-cause mortality. Metastatic disease was approximately twice as likely in the active surveillance group, with an excess of 3.5 more diagnoses of metastatic disease per 1,000 person-years. Patients receiving active surveillance were more likely to start androgen-deprivation therapy (9.4 vs. 5.3 to 5.6 per 1,000 person-years) and experience any clinical progression, which included metastasis, progressing to T3 or T4, requiring androgen deprivation, or having anatomic complications due to tumor growth. By 15 years, approximately 40% of men were able to avoid radiotherapy or surgery.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: Hamdy FC, Donovan JL, Lane JA, et al.; ProtecT Study Group. Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med. 2023;388(17):1547-1558.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.