Post-surgical pathology, active surveillance, and selection of appropriate candidates for expectant management

An interesting — if unsurprising — new set of data in the Journal of Korean Medical Science has again shown that most of the current “standard” sets of criteria for selection of patients aren’t even close to being perfect at identification of “the surgically ideal” patients for management on active surveillance.

Kang et al. report the results of a retrospective analysis of data from 312 patients, all of whom had D’Amico low-risk prostate cancer (clinical stage T2a or lower, and a PSA of < 10 ng/ml, and a Gleason score of 6 or less) at the time of diagnosis but underwent radical prostatectomy as treatment for their cancer at a single Korean institution between 2007 and 2013.

First, they looked at whether these 312 patients met one or more of five well known but slightly different sets of criteria for management on active surveillance:

  • The Johns Hopkins Medical Institution (JHMI) criteria
  • The Memorial Sloan-Kettering Cancer Center (MSKCC) criteria
  • The European PRIAS (PRIAS) criteria
  • The University of California, San Francisco (UCSF) criteria
  • The University of Miami (UM) criteria

(Note that they did not include the University of Toronto, Sunnybrook, criteria used by Klotz and his colleagues in Canada.)

They then looked at whether the patient’s pathological outcomes post-surgery correlated with the clinical criteria pre-treatment. To do this, they defined pathologically insignificant prostate cancer as being

  • Completely organ-confined, with
  • A Gleason score of 3 + 3 = 6 or lower (i.e., no sign of Gleason pattern 4 or 5 disease), and
  • A total tumor volume of < 0.5 cm3

Unsurprisingly, a significant percentage of their patients did not meet these criteria. Here are the findings:

  • 205/312 patients were actually eligible for analysis (because 107 patients either had < 10 biopsy cores taken at time of diagnosis or received some form of neoadjuvant treatment prior to their surgery).
  • Of the 205 eligible patients
    • 70 (34.1 percent) met the JHMI criteria, and 55/70 (78.6 percent) had pathologically insignificant disease.
    • 161 (78.5 percent) met the MSKCC criteria, and 119/161 (73.9 percent) had pathologically insignificant disease.
    • 109 (53.2 percent) met the PRIAS criteria, and 79/109 (72.5 percent) had pathologically insignificant disease.
    • 141 (68.8 percent) met the UCSF criteria, and 104/141 (73.8 percent) had pathologically insignificant disease.
    • 96 (46.8 percent) met the UM criteria, and 72/96 (75.0 percent) had pathologically insignificant disease.
    • 168 (82.0 percent) met at least one of the five sets of criteria, and 123/168 (73.2 percent) had pathologically insignificant disease.
    • Only 29 (14.1 percent) met all five sets of criteria, and 24/29 (82.8 percent) had pathologically insignificant disease.
    • 37 (18 percent) didn’t meet any of the five sets of criteria, but 12/37 (32.4 percent) still had pathologically insignificant disease.
    • 56/205 men (27.3 percent) had a pathological finding of Gleason 3 + 4 = 7 or higher post-surgery.
    • 26/205 men (12.7 percent) had non-organ-confined disease post-surgery.
    • 135/205 men (65.9 percent) had pathologically insignificant prostate cancer post-surgery.

Exactly what these data “mean” is somewhat difficult to determine because no one should have expected any — or all — of the five sets of criteria to be able to predict histopathologically insignificant prostate cancer with 100 percent certainty. Active surveillance as a management strategy is not intended to guarantee that a patient will never need treatment. It is intended to avoid over-treatment and the consequences of over-treatment by deferral of treatment until it is apparent that treatment would be wise. (For some patients, of course, this does mean that the only form of management they will ever need in their lifetimes is active surveillance.)

Here are some of the things that The “New” Prostate Cancer InfoLink sees as important in thinking about this study, which is certainly (as indicated previously) interesting, and which we should be able to learn from:

  • There was one arguably surprising finding, which is that 12/205 men (5.9 percent) who didn’t meet any of the five sets of criteria for active surveillance still had pathologically insignificant prostate cancer post-surgery. But this raises the question of whether these 12 men would have met the Klotz/Sunnybrook criteria.
  • The highest level of pathologically insignificant prostate cancer (82.8 percent) occurred in men who met all five sets of criteria for management on active surveillance — but even among men who met all five criteria, there were still some who didn’t have pathologically insignificant disease.
  • As one might have expected, the stringent JHMI criteria were best at predicting which men would have pathologically insignificant disease … but JHMI has already implied that it’s criteria for entry onto active surveillance protocols may be overly stringent.
  • Patients in this study did not get any type of prospective re-evaluation after initial diagnosis and prior to surgery (using either a careful re-biopsy or an MRI or both) to ensure that they really were good candidates for active surveillance … so some of them probably weren’t!

This study is only one of several published studies to conduct this type of analysis, but it does appear to be the first to identify the fact that a small subset of patients not meeting any of the selected sets of criteria for active surveillance can, in fact, have histopathologically insignificant prostate cancer (as defined by the authors). Such studies are certainly helpful in guiding us with respect to the future standardization of clinical criteria for selection of patients appropriate for  management on active surveillance.

However, like most other studies of this type, what this study really shows is that:

  • We need better standardization of clinically appropriate (as opposed to academically interesting) criteria for placing men on active surveillance.
  • We need to incorporate the use of standardized forms of diagnostic re-evaluation into these criteria (e.g., multiparametric MRIs and repeat biopsies within 12 months of diagnosis, ideally based on multiparametric MRI/TRUS fusion).
  • We need to fully appreciate that outcomes of management on active surveillance must be assessed on the same clinical basis as every other form of management for localized prostate cancer — progression-free survival at 5 and 10 years of follow-up — as opposed to any type of histopathological outcome among men who were not managed on active surveillance at all!

2 Responses

  1. I question the significance of the accuracy of JHMI vs. the others given the disparate rate of men meeting their requirements for AS compared with the others. In other words it looks to me like a guy would have had the best odds of going to MSKCC if he was interested in active surveillance based on these data.

  2. Dear Cliff:

    I was talking about something different to you. You are correct that if you wanted to get onto active surveillance, the MSKCC criteria permit enrollment of a wider range of patients. The JHMI criteria, on the other hand, were the best at projecting pathologically indolent disease according to the criteria predefined by this group of authors in this cohort of patients. However, the real question to be addressed is whether any of the criteria used in this study are actually the most appropriate criteria from a clinical perspective. The modified criteria now being used by Klotz and his colleagues in Canada permit enrollment of an even wider range of patients that the MSKCC criteria but appear to be able to produce long-term outcomes closely comparable to those recently published by Johns Hopkins.

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