Questioning the Status Quo: Should Gleason Grade Group 1 Prostate Cancer be Considered A “Negative Core” in Pre-Radical Prostatectomy Risk Nomograms? An International Multicenter Analysis – Beyond the Abstract

Pre-radical prostatectomy (RP) risk nomograms for prostate cancer (PCa) have been constructed to provide prognostic information regarding a patient’s oncologic outcomes. Specifically, these nomograms predict the risk of lymph node involvement (LNI) in PCa patients, which subsequently informs a surgeon’s decision to perform pelvic lymph node dissection (PLND) at the time of RP.1,2 In the current era, where Gleason Grade Group (GG) 1 PCa is increasingly deemed clinically insignificant, established nomograms may be suboptimal in estimating final RP pathology outcomes for men diagnosed with PCa.

We performed a multicenter international (USA, Canada, and Germany) analysis examining the impact of excluding Gleason GG1 PCa scores from current pre-RP nomograms and its predicted outcomes. Intuitively, we found that excluding GG1 PCa cores predicted more favorable nomogram outcomes, as doing so decreases the total percentage of positive cores, thereby decreasing predicted cancer burden.

Importantly, when validated against final RP pathology, exclusion of GG1 PCa also yielded a better approximation of final RP pathology for LNI, extracapsular extension (ECE) and organ-confined disease (OCD), but not seminal vesicle invasion (SVI). The same results were seen when looking at the subset of men with GG2-5 PCa with concurrent GG1 disease on prostate biopsy. Fortunately, while SVI represents an adverse prognostic factor in PCa staging, it has not been shown to be uniformly associated with poor outcomes in PCa patients as it is not the most significant clinicopathologic characteristic in predicting PCa recurrence when compared to other features such as LNI.3

Lastly, clinically significant impact on management, defined as a change in LNI risk above or below 2% or 5% (Δ2/Δ5), was assessed based on international guideline recommendations that may impact a surgeon’s decision to perform PLND.4,5 Notably, exclusion of GG1 PCa cores significantly decreased predicted LNI nomogram risk, and subsequently reduced the need for the performance of PLND in up to 31% of GG1 patients and 22% of GG2 patients.

Ultimately, the consistently better predictive ability of these nomogram outcomes when excluding GG1 PCa calls into question its inclusion in PCa nomogram development. Furthermore, it highlights the indolent nature of GG1 PCa and the fact that it is likely not a driver of disease.

While these nomograms were historically developed based on systematic 12-core prostate biopsies (PBx), future directions include validating our results in a homologized, prospective cohort, as well as in the setting of MRI-fusion targeted biopsies, prior to the amendment of these risk stratification tools.6

Written by: Joon Yau Leong, BS, Thenappan Chandrasekar, MD, Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA, USA.

References:

  1. Briganti A, Larcher A, Abdollah F, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol. 2012;61(3):480-487.
  2. Memorial Sloan Kettering Cancer Center. Pre-Radical Prostatectomy Nomograms. https://www.mskcc.org/nomograms/prostate/pre_op. Accessed 01 September 2018.
  3. Kristiansen A, Drevin L, Delahunt B, et al. Prognostic significance and biopsy characteristics of prostate cancer with seminal vesicle invasion on radical prostatectomy: a nationwide population-based study. Pathology. 2017;49(7):715-720.
  4. Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate Cancer, Version 1.2016. J Natl Compr Canc Netw. 2016;14(1):19-30.
  5. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017;71(4):618-629.
  6. Leong JY, Herrera-Caceres JO, Goldberg H, et al. Incorporating mpMRI biopsy data into established pre-RP nomograms: potential impact of an increasingly common clinical scenario. Ther Adv Urol. 2019;11:1756287219882809.
Read the Abstract