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Active Surveillance Should Not Be Routinely Considered in ISUP Grade Group 2 Prostate Cancer - Beyond the Abstract

It is well established that active surveillance for low-risk (Grade Group 1, Gleason 3+3) prostate cancer has excellent long-term oncologic outcomes. Therefore, international guidelines recommend it as the standard of care for the treatment of low-risk disease. Much less is known for patients with contemporary high-grade cancer (mostly Grade Group 2, Gleason 3+4).

We were invited by BMC Urology in a “pro and con” comprehensive review of the literature on active surveillance for intermediate-risk and Grade Group 2 prostate cancer in parallel with the team led by Dr. Carlsson and Dr. Pekala, who represented the “pro” counterpart.1

We specifically looked at current evidence in terms of randomized trials and observational studies evaluating the association between high-grade cancer and oncologic outcomes. Level one evidence, although limited by non-contemporary grading of prostate cancer, shows that survival benefits of treatment versus observation are modest. However, the incidence of metastases in men on active monitoring in the ProtecT trial prompts caution when sharing decision making with patients harbouring intermediate-risk features willing to pursue active surveillance.2

In terms of observational evidence, it is clear that Gleason pattern 4 drives the risk of metastases and mortality.3 However, the pivotal question is how much pattern 4 is acceptable to put a man on active surveillance and still not miss his window of curability. It appears that there is significant overlap in the total amount of pattern 4 between Grade Groups at radical prostatectomy, supporting the concept of its absolute quantification rather than measuring its ratio compared to pattern 3.4 However, current guidelines do not yet recommend this approach in the reporting of pathology specimens. Hereof, it is plausible that patients with little pattern 4 may be safely monitored, and sent to curative intent treatment once they progress.5 It is our opinion that until precise tools aiding clinical decision making are available, such as a standardized way of measuring total amount of pattern 4 on biopsies, routinely considering active surveillance in all men with Grade Group 2 disease is simply not safe enough, and shall be a matter of clinical judgment and shared decision making. Like active surveillance for low-grade prostate cancer, monitoring of patients with intermediate-risk disease shall be initially pursued at academic institutions.

Written by: Riccardo Leni, MD,1,2 & Giorgio Gandaglia, MD, FEBU,3,4

  1. Unit of Urology/Division of Oncology; URI, IRCCS Ospedale San Raffaele, Milan, Italy
  2. Vita-Salute San Raffaele University, Milan, Italy
  3. Unit of Urology/Division of Oncology; URI, IRCCS Ospedale San Raffaele, Milan, Italy
  4. Vita-Salute San Raffaele University, Milan, Italy
References:

  1. Pekala KR, Bergengren O, Eastham JA, Carlsson S V. Active surveillance should be considered for select men with Grade Group 2 prostate cancer. BMC Urol 2023;23:152.
  2. Hamdy FC, Donovan JL, Lane JA, Metcalfe C, Davis M, Turner EL, et al. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med 2023.
  3. Sauter G, Steurer S, Clauditz TS, Krech T, Wittmer C, Lutz F, et al. Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens. Eur Urol 2016;69:592–8.
  4. Andolfi C, Vickers AJ, Cooperberg MR, Carroll PR, Cowan JE, Paner GP, et al. Blood Prostate-specific Antigen by Volume of Benign, Gleason Pattern 3 and 4 Prostate Tissue. Urology 2022;170:154–60.
  5. Dean LW, Assel M, Sjoberg DD, Vickers AJ, Al-Ahmadie HA, Chen Y-B, et al. Clinical Usefulness of Total Length of Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer. J Urol 2019;201:77–83.
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