Prostate cancer grading, time to go back to the future

Egevad, Lars; Delahunt, Brett; Bostwick, David G.; Cheng, Liang; Evans, Andrew; Gianduzzo, Troy; Graefen, Markus; Hugosson, Jonas; Kench, James G.; Leite, Kátia R. M.; Oxley, Jon; Sauter, Guido; Srigley, John R.; Stattin, Pär; Tsuzuki, Toyonori; Yaxley, John; Samaratunga, Hemamali

doi:10.1111/bju.15298

Cited by 7 publications

(8 citation statements)

References 41 publications

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“…So far, the best prognostic biomarkers in prostate cancers are based on morphological alterations, defined by Gleason grading, or PSA levels. However, there is ongoing debate about the appropriateness of combining the various combinations of Gleason scores to make grade groups 4 and 5 and whether or not these stratifications capture all the potential richness from pathological assessment 29 . Part of the uncertainty may be due to the relatively small proportion of patients with high grade cancers included in reported studies.…”

Section: Discussionmentioning

confidence: 99%

“…The IMRT trial focuses on locally-advanced prostate cancers with generally high Gleason score. These may not be adequately stratified by Gleason grade or ISUP grade grouping 29 which in general have been derived from surgically treated cohorts with less advanced cancers 1 . We confirmed that neither the original scoring of the pathologist, nor re-scoring by a single expert demonstrated a statistically significant trend in ISUP grade groups (Figure 4F).…”

Section: Spatial Morphological Heterogeneity Measured With Deep Learn...mentioning

confidence: 99%

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Tumour evolvability metrics predict recurrence beyond 10 years in locally-advanced prostate cancer

Sottoriva¹,

Fernandez-Mateos²,

Cresswell³

et al. 2022

Preprint

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Cancers evolve obeying Darwinian laws and therefore the evolutionary paradigm lays the ground for predictive oncology. However, the predictive power of evolutionary metrics in cancer has been seldom tested. There is a need for quantitative measurements in controlled clinical trials with long term follow-up information. This is particularly true in locally-advanced prostate cancer, which can recur more than a decade after diagnosis. Here we mapped genomic intra-tumour heterogeneity in 642 samples from 114 patients who took part in the prostate radiotherapy trials at The Royal Marsden Hospital, for which full clinical information and 12y median follow-up was available. We concomitantly assessed phenotypic (morphological) heterogeneity using deep learning in 1,923 histological sections from 250 IMRT patients (fully overlapping with the genetic set). We found that evolvability, measured as genetic divergence as well as morphological diversity, was a strong independent predictor of recurrence (respectively HR=72.06, 95% CI 2.97-1748.5, p=0.009 and HR=6.2, 95% CI 1.86-20.72, p=0.003). Combined, these two measurements together also identified a group of patients with half the median time to recurrence compared to the rest of the cohort (5.6 vs 11.5 years). We also found a small subset of MYC/FGFR1 amplified cases (4.4%) with particularly poor prognosis. The overall burden of chromosomal alterations correlated with higher Gleason score. We identified associations between 24 chromosomal arm copy number changes and Gleason score (e.g. -22q, +5p, +8q, +16p, +7p), and show that loss of chromosome 6p (encompassing the HLA locus) was correlated with markedly reduced immune cell infiltration. This study shows that combining genomics with AI-aided histopathology in clinical trials leads to the identification of novel clinical biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Spatial Morphological Heterogeneity Measured With Deep Learn...mentioning

confidence: 99%

Tumour evolvability metrics predict recurrence beyond 10 years in locally-advanced prostate cancer

Sottoriva¹,

Fernandez-Mateos²,

Cresswell³

et al. 2022

Preprint

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“…During the study period the Gleason scoring reflected the changes in cancer grading based on the grading criteria of the modified Gleason grading system [ 10 ] and the 2014 International Society of Urological Pathology (ISUP) grading system [ 11 ]. We continue to report using the Gleason scoring system, as collapsing the Gleason grading system to five groups simplifies the complexity of prostate cancer morphology, with resulting loss of detail of information [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

Oncological and urinary outcomes following low‐dose‐rate brachytherapy with a median follow‐up of 11.8 years

et al. 2022

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Objectives To examine the long‐term oncological outcomes and urological morbidity of low‐dose‐rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate‐risk prostate cancer. Patients and Methods A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side‐effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate‐specific antigen (PSA) level of ≥0.2 μg/L. Results Minimum patient follow‐up was 5.5 years. The median follow‐up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9–17) μg/L and the median Gleason score was 3 + 4. The biochemical relapse‐free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a ‘surgical’ definition of a PSA level of <0.2 μg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer‐specific survival (PCSS) was 98% (291/297). Post‐LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow‐up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT. Conclusion LDRBT is associated with excellent PCSS, with a median follow‐up of 11.8 years. The risk of post‐implantation urethral stricture and UI is low and a pre‐implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture.

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“…In a recent contribution entitled “Prostate cancer grading, time to go back to the future,” Egevad et al 27 “question the cost–benefit ratio of the putative pedagogical advantage vs. the confusion that has been caused by the plethora of new terms.” To them, the notion that this would be a novel grading system is a misconception as it is a mere translation of the Gleason scores into an alternative terminology, that is, grade groups. They conclude that “it is time to realize that the introduction of such grouping was a mistake and reclaim the universally understood Gleason nomenclature for grading of PCa.”…”

Section: Pca Grading: Gleason Grading System(s): Isup and Later On Gupsmentioning

confidence: 99%

Histopathology of Prostate Cancer and its Precursors

Montironi

Cimadamore

Mazzucchelli

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Starting in the mid-1970s, we formed a group of pathologists with a major interest in uropathology. Originally, it included 2 (R.M. and M.S.). In the years the followed, the group was enlarged to include 4 more people, 2 in the mid- and late-1980s (A.L.B. and L.C.) and another in the mid-1990s (R.Ma.); a sixth (A.C.) joined the group ∼5 years ago. Two have reached the retirement age (R.M. and M.S.), while others are in the process of joining the group to replace them. A fruitful collaboration spanned for ∼45 years. This contribution is based on a series of personal recollections of the successive changes in the interpretation of prostate cancer and its precursors, starting in the mid-1970s. Here we have retraced our involvement steps, sharing issues related to them with a junior uropathologist (A.C.).

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Prostate cancer grading, time to go back to the future

Cited by 7 publications

References 41 publications

Tumour evolvability metrics predict recurrence beyond 10 years in locally-advanced prostate cancer

Tumour evolvability metrics predict recurrence beyond 10 years in locally-advanced prostate cancer

Oncological and urinary outcomes following low‐dose‐rate brachytherapy with a median follow‐up of 11.8 years

Histopathology of Prostate Cancer and its Precursors

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