Wednesday, March 5, 2014

Active Surveillance for Prostate Cancer: 16 years of Knowledge Gained

H. Ballentine Carter, MD
H. Ballentine Carter, Professor of Urology and Oncology at the Brady, initiated the Active Surveillance (AS) Program for Prostate Cancer at Johns Hopkins 16 years ago.  This was one of the first of its kind and is now among the longest-running AS program for prostate cancer in the world.

There have been a variety of important questions answered and lessons learned over the past two decades. First, at 10 years approximately 60% of patients will undergo some intervention for prostate cancer.  The prompt for intervention is a change in Gleason score or increase in volume of disease in 75%.  Importantly, no patient had died of prostate cancer (median follow-up 6.5 years, maximum 15 years).[1]

Jeff Tosoian, MD
Second, figuring out who will "progress" and have worse prostate cancer while on AS can be difficult.  To be enrolled in the Active Surveillance Program at Hopkins, a man must have low-grade and small-volume disease – cancer categorized as "very low risk" (see below for defintions) .  Jeff Tosoian, M.D., a urology resident at the Brady, studied men with very low-risk and low-risk disease who underwent surgery at Hopkins. "Since they underwent surgery, it was possible to compare the extent of cancer in the two groups," says Carter. After evaluating the extent of cancer among 7,333 men classified as low-risk, and 153 men diagnosed with very low-risk disease, Tosoian concluded that men with low-risk disease were approximately two times more likely than very low-risk men to have a cancer that turned out to be of higher grade and/ or to have spread beyond the prostate gland. "This finding suggests that surveillance may be more risky in the presence of low-risk versus very low-risk disease, especially in younger men," says Carter. "Men who can expect to live at least 20 more years who have low-risk disease may rather accept the risks of treatment than take the chance that their cancer will cause harm later, especially if they are otherwise healthy. Men with very low-risk disease can take comfort that their disease can safely be managed by surveillance."[2]

Low Risk Prostate Cancer

  • PSA is below 10 ng/ml
  • Biopsy has a Gleason score of 6
  • Cancer is not palpable or is minimally palpable on a digital rectal examination

Very-Low Risk Prostate Cancer

  • Your biopsy has a Gleason score of 6,
  • 2 cores or fewer are found to contain cancer,
  • Cancer makes up half or less of any core that contains cancer,
  • PSA divided by the prostate volume is 0.15 or less, and
  • Cancer is not palpable on a digital rectal examination

Third, determining the potential benefits of RP or AS can be difficult since no trial directly compares surgery (radical prostatectomy, RP) to AS.  Therefore, complex simulation models need to be employed to detect potential benefits among patients undergoing either RP or AS.  Investigators from Hopkins, the Fred Hutchinson Cancer Center, and the University of California-San Francisco (UCSF) teamed up to compare the outcomes of men enrolled in the AS Program at Hopkins with those of men who underwent surgery immediately at Hopkins and UCSF after their cancer was diagnosed. The scientists projected that 2.8 percent of men on AS and 1.6 percent of the men who underwent immediate RP would die of their disease in 20 years. They estimated that the average increase in life expectancy associated with immediate RP was 1.8 months, and that men on AS would remain free of treatment for an additional 6.4 years as compared to men who had immediate treatment. "These findings suggest that men enrolled in the Johns Hopkins AS Program are at low risk of losing a window of opportunity for cure if they are carefully monitored," Carter says.[3]

Some of this blog has been extracted from Prostate Cancer Discovery, Volume 10, Winter 2014.

1. Tosoian JJ, Trock BJ, Landis P, Feng Z, Epstein JI, Partin AW, Walsh PC, Carter HB.Active surveillance program for prostate cancer: an update of the Johns Hopkins experience.J Clin Oncol. 2011 Jun 1;29(16):2185-90. doi: 10.1200/JCO.2010.32.8112. Epub 2011 Apr 4.
2. Tosoian JJ, JohnBull E, Trock BJ, Landis P, Epstein JI, Partin AW, Walsh PC, Carter HB.Pathological outcomes in men with low risk and very low risk prostate cancer: implications on the practice of active surveillance.J Urol. 2013 Oct;190(4):1218-22. doi: 10.1016/j.juro.2013.04.071. Epub 2013 Apr 30.
3.  Xia J, Trock BJ, Cooperberg MR, Gulati R, Zeliadt SB, Gore JL, Lin DW, Carroll PR, Carter HB, Etzioni R.Prostate cancer mortality following active surveillance versus immediate radical prostatectomy. Clin Cancer Res. 2012 Oct 1;18(19):5471-8. doi: 10.1158/1078-0432.CCR-12-1502. Epub 2012 Sep 24.

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