Refining the criteria for selection of patients suitable for active surveillance

The question of how best to set the spectrum of criteria that indicate the suitability of an individual patient as a good candidate for active surveillance as opposed to early treatment is (as yet) not well answered. Indeed, in August 2015 Carroll and Dall’Era clearly stated that the development of a “one size fits all” approach may not even be wise (see this link).

In a newly published paper in Prostate Cancer and Prostatic Diseases, Iremashvili et al. compared the abilities of five different methods in current use to select good candidates for active surveillance. The five methods are:

  • Use of one of the Kattan nomograms, which was developed specifically to project risk for the presence of pathologically indolent prostate cancer (see Kattan et al.)
  • Use of the Truong nomogram, which was developed to project risk for a pathological upgrade in men initially diagnosed with a Gleason score of < 7 (see Truong et al.)
  • Use of the original, very stringent Johns Hopkins criteria for enrollment into its active surveillance protocol (clinical stage T1c; PSA density ≤0.15 ng/ml/ml; ≤ 2 positive biopsy cores; ≤ 50 percent maximal cancer involvement in any core)
  • Use of the significantly less stringent UCSF criteria (clinical stage T1c or T2; PSA ≤ 10 ng/ml; ≤ 33 percent of biopsy cores positive for cancer; ≤ 50 percent maximal cancer involvement in any core)
  • Use of the Prostate Cancer Research International Active Surveillance or PRIAS criteria (clinical stage T1c or T2; PSA density ≤ 0.2 ng/ml/ml; ≤ 2 positive biopsy cores)

(Note that neither this particular Kattan nomogram nor the Truong nomogram are currently available in a web-enabled, user-friendly, data entry format for a patient or a physician to use; thus using these normograms requires some significant effort.)

The authors used data from a study cohort of 402 patients, all treated by open or robot-assisted laparoscopic surgery at the University of Miami, and mostly after the year 2000, to compare the ability of the five different methods to predict two pathologic endpoints:

  • The presence of a pathologic Gleason score of ≤ 3 + 3 = 6 post-surgery
  • The presence of a pathologic Gleason score of ≤ 3 + 4 = 7 post-surgery

The authors are very clear that their study has numerous limitations that we will refer to below. However, their two basic findings seem to be relatively clear, as follows:

  • Use of the PRIAS criteria to select patients for active surveillance offered the best balance between sensitivity and specificity in identifying patients with low-grade, organ-confined prostate cancer.
  • The two nomograms may be better able to select more patients with the same risk for non-organ-confined and/or high-grade prostate cancer compared to the Johns Hopkins and the UCSF criteria.

The “New” Prostate Cancer InfoLink is equally clear that we are still going through an evolutionary process in the attempt to best identify those patients who are “the best” candidates for active surveillance — and an individual patient’s willingness to accept certain types of risk is very much a key part of the relevant criteria. From that perspective, we consider that some of the points originally made by Carroll and Dall’Era in their discussion about the selection of patients for active surveillance are critical, but the data presented by Iremashvili et al. are also valuable.

Newer methods appear to be improving our ability to ensure accurate information about which patients may be good candidates for active surveillance, and there is increasing understanding that active surveillance is not simply a management option designed to select men who will “never” need treatment because they are at no risk at all of dying from prostate cancer. Rather, active surveillance is a method designed to defer treatment (as and when appropriate) for as long as possible among men who do not need immediate treatment.

Some or perhaps all of the following methods can now be used to help to identify good candidates for active surveillance:

  • Multi-parametric MRI scanning
  • MRI/TRUS fusion-guided biopsies
  • Various genetic/genomic tests (e.g., the Oncotype DX and Prolaris tests and others)

As yet, we have no level 1 data on the accuracy of these tests in prediction of relatively indolent forms of prostate cancer and we have no nomograms or other criteria that allow us to formally “predict” for relatively indolent forms of prostate cancer based on data from such test results. This is the inevitable and major limitation on the data evaluated by Iremashvili et al.

A decade from now, we may be able to predict for clinically insignificant prostate cancer with a much higher degree of accuracy than we can today. Because of the very nature of the disease in most patients, prostate cancer research can take a long time. For the time being, we have at least discovered that active surveillance “works well” for carefully selected patients … but “perfecting” the selection process may be a difficult accomplishment because there will always be a degree of unpredictable and individual variation in the behaviors of particular forms of prostate cancer in particular types of patient.

Editorial note: The “New” Prostate Cancer InfoLink thanks Dr. Viacheslav Iremashvili of the University of Miami for providing us with a full-text copy of the above-mentioned paper for our review.

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