“Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients with Prostate Cancer” was reported by Dr. Laurence Klotz and colleagues, University of Toronto, in the January 2015 issue of the Journal of Clinical Oncology. It is the largest study of active surveillance (AS) with the longest follow-up (median 6.4 years, range 0.2-19.8 years) tracking 993 men with low- or intermediate-risk prostate cancer. It reports very favorable outcome data, but also suggests methods for further improvement.

Executive Summary:

  1. The 10- and 15-years actuarial prostate cancer-specific survivals were 98.1% and 94.3%.
  2. “At 5, 10, 15, and 20 years, 75.7%, 63.5%, 55%, and 55% of patients remained untreated and on surveillance.
  3. Metastatic disease developed in 2.8% of the men at a median time of 9.6 years after diagnosis, and 1.5% died of prostate cancer. Of the 28 men developing metastasis, 44% were Gleason 7 at diagnosis.
  4. The authors noted: “This mortality rate is consistent with expected mortality in favorables-risk patients managed with initial definitive intervention.”
  5. Overall survival rates were 80% and 62% at 10 and 15 years.
  6. The ratio of deaths from non-prostate causes to prostate related deaths was 9 to 2.1.

Patient Selection Criteria and Method of Follow-Up:

Initially (1995-1999), eligibility required a Gleason score < 6 and PSA < 10 ng/mL (Gleason score < 3 + 4 and PSA < 15 ng/mL for men older than 70 years). Since January 2000 the eligibility of men with favorable intermediate-risk cancer was restricted to men with estimated longevity of < 10 years with PSA 10 – 20 ng/mL and/or Gleason score 3 + 4.

Gleason score was < 6 in 84% and Gleason 7 in 13%, with 21% being intermediate-risk. Median age was 67.8 years.

Follow-up consisted of PSA testing every 3 months for 2 years then at 6 months. A confirmatory 14 core biopsy was performed within a year of diagnosis, then every 3 to 4 years.

Reasons for Intervention:

  1. A PSA doubling time < 3 years, at first the sole trigger intervention, later became only an indicator for closer evaluation, such as with a multiparametric MRI with biopsy as indicated.
  2. Intervention occurred in 43.5% of men due to short PSA doubling time (PSA DT).
  3. Increase in histologic grade on subsequent biopsy led to treatment in 35%.
  4. Clinical progression, such as developing a palpable nodule on DRE confirmed as cancer was an indication for treatment.
  5. Patient preference occasioned treatment in 6%.

Outcome of Intervention in Men Who Were Treated:

PSA failure (set at >0.2 ng/mL after prostatectomy and PSA nadir plus 2 ng/mL following radiation) developed in 25% (249 men) of the total cohort.  Biochemical disease-free survival following treatment for these 249 men at 5 and 10 years was 77% and 60%. Men with a PSA doubling time of <3 years before treatment had a 7.8-fold greater likelihood of biochemical recurrence after treatment compared to those with pretreatment PSADT of > 3 years, “supporting the concept that PSADT is a marker of aggressive disease.”

The median follow-up of 6.4 years is relatively short for the usually indolent course of low-risk prostate cancer, but in this study 200 men have been followed for >10 years lending credibility to the outcome data.

BOTTOM LINE:

“Active surveillance is an evolving strategy. The major limitation is that a significant proportion of patients diagnosed with Gleason score 6 cancer harbor higher-grade disease” (Klotz, ibid). Despite the encouraging outcomes reported in this study, improvement may be achieved in the future by incorporating multiparametric MRI, targeted biopsies, and molecular biomarkers into the selection process.

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