Pathology of prostate cancer in patients after active surveillance

With the increasing acceptance of active surveillance as a management strategy for men initially diagnosed with low-risk prostate cancer, it is increasingly important to have a detailed understanding of how these men fare over time, most particularly among those who have subequent progression that needs treatment.

Duffield et al. have reported data on 51/470 men who had a radical prostatectomy after initial participation in an active surveillance program at Johns Hopkins Medical Center in Baltimore. All patients on the prtotocol were given an annual repeat needle biopsy. Under this protocol, disease progression was defined as evidence of any amount of Gleason pattern grade 4/5 tumor; occurence of cancer in > 50 percent of any single core; or or occurrence of cancer in > 2 cores.

The results of this study showed the following:

  • Pathology slides were available and were reviewed for 48/51 patients who had radical prostatectomies after progression.
  • The average time between the initial (diagnostic) prostate biopsy and radical prostatectomy was 29.5 months (range 13 to 70 months).
  • 21/48 patients (44 percent) showed progression at the time of their second biopsy.
  • 36/48 patients (75 percent) showed progression by the time of their third biopsy.
  • 31/48 cases (65 percent) were organ confined cases, of which 25 (52 percent) were Gleason score 6.
  • 17/48 cases (35 percent) indicated extraprostatic extension, of which 3 (6 percent) showed seminal vesicle or lymph node involvement and 7 (15 percent) showed positive margins.
  • 13/48 tumors (27 percent) were potentially clinically insignificant (organ confined, dominant nodule < 0.5 cm3 in volume, no Gleason pattern 4/5).
  • 5/26 (19 percent) of the patients who had radical prostatectomies with a dominant tumor nodule < 0.5 cm3 in volume had extraprostatic extension, 4 with Gleason pattern 4.
  • All 10 patients with tumors with a dominant nodule > 1 cm3 in volume were located predominantly at the anterior of the prostate.

The authors state the following series of conclusions:

  • Most disease progression after active surveillance occurs 1 to 2 years after diagnosis.
  • This suggests that progression is a consequence of initial undersampling of more aggressive tumors rather than progression of indolent tumors.
  • Even with progression, most tumors have favorable pathology, with 27 percent of tumors being potentially insignificant in this study.
  • A small percentage of men do indeed ave advanced stage disease (pT3b or pN1).
  • In men undergoing active surveillance, the anterior region of the prostate should be specifically be sampled on repeat biopsies.

We are going to need a great deal more data of this type, with patients being followed over significantly longer periods of time, in order to be able to get the best possible perspective about risk management in men undergoing active surveillance protocols, but these data, indicating that just 51/470 men in the Johns Hopkins active surveillance series (11 percent) have gone on to have a radical prostatectomy within roughly a 3-year follow-up period, continue to offer strong evidence of the potential of this management technique.

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