Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance

Nyame, Yaw A.; Grimberg, D; Greene, Daniel; Gupta, Karishma; Kartha, Ganesh; Berglund, Ryan K.; Gong, Michael C.; Stephenson, Andrew J.; Magi‐Galluzzi, Cristina; Klein, Eric A.

doi:10.1016/j.juro.2017.09.077

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…While this cohort had a higher percentage of IR category cases, the 25% NCCN risk category reclassification rate with the GPS test is similar to previously reported reclassification rates 5,6 . While no significant difference was seen in the percentage of patients in each NCCN risk category change group who underwent prostatectomy, a large number of other factors were used to determine which patients underwent definitive therapy, including UCSF‐CAPRA score, 30 absolute GPS, and imaging findings, which confounds the use of treatment as an outcome measure here.…”

Section: Discussionsupporting

confidence: 70%

“…It can be argued that GPS is most useful when it results in NCCN risk category reclassification, as this may affect patient management. Previous studies have examined the effect of GPS on NCCN risk category reclassification, with reports showing approximately one‐quarter 5 to one‐third 6 of patients having reclassification upon addition of the test. It is not clear why some cases are reclassified as a result of this molecular testing.…”

Section: Introductionmentioning

confidence: 99%

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Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category

et al. 2020

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Background: For biopsies with Gleason 3 + 3 = 6 or 3 + 4 = 7 prostate cancer, the Genomic Prostate Score (GPS; OncotypeDx) is designed to predict severe pathology at prostatectomy, and, in some cases, recommends reclassification of the National Comprehensive Cancer Network (NCCN) risk category. We hypothesized that certain histopathologic features that were not considered in the original design of the assay actually would be associated with the NCCN risk category change indicated by GPS testing. Methods: For patients with recommended NCCN risk category change, the biopsy cores used for GPS were re-reviewed for stromal reaction, chronic inflammation, and tumor nuclear polarization. Results: Of 520 patients from May 2011 to December 2018, GPS testing suggested NCCN risk reclassification in 131 (25%); 127 of these slides were available. Of these, the NCCN risk category increased from intermediate to high in 8, low to intermediate in 15, very low to low in 1, and decreased from intermediate to low in 32, and low to very low in 71. Biopsies with NCCN risk increase were associated with moderate or severe stromal reaction (p < .001) and chronic inflammation (p < .001); biopsies with NCCN risk decrease were associated with absence of these features. In Gleason 3 + 3 = 6 cases (n = 93), presence of nuclear polarization was associated with NCCN risk decrease and its absence with increase (p < .001). Conclusions: Moderate or severe stromal reaction, chronic inflammation, and lack of nuclear polarization in Gleason score 3 + 3 = 6 tumors were each associated with an increase in NCCN risk category indicated by GPS and vice versa. Our results suggest that GPS captures histologic features associated with aggressiveness that are not routinely assessed in standard histopathologic assessments, and that consideration of such histologic features may improve upon current tumor grading approaches.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category

et al. 2020

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“…In addition, our present finding that pathological upgrading was common regardless of tumour volume is consistent with a recent publication examining the association between disease reclassification by genomic classifiers and biopsy tumour volume. That analysis of men with very-low- and low-risk prostate cancer at diagnosis determined that genomic disease reclassification was independent of biopsy tumour volume [16]. Last, our determination that the frequency of upgrading and adverse pathological features on RP specimens was significantly higher for patients with unreassuring compared to reassuring confirmatory test results highlights that confirmatory test results are providing the patient and physician with valuable and reliable information, and that patients and/or physicians are acting on the confirmatory test results.…”

Section: Discussionmentioning

confidence: 99%

Pathological upgrading at radical prostatectomy for patients with Grade Group 1 prostate cancer: implications of confirmatory testing for patients considering active surveillance

Kaye

Morgan

et al. 2018

BJU International

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Objective To examine the association between National Comprehensive Cancer Network (NCCN) risk, number of positive biopsy cores, age, and early confirmatory test results on pathological upgrading at radical prostatectomy (RP), in order to better understand whether early confirmatory testing and better risk stratification are necessary for all men with Grade Group (GG) 1 cancers who are considering active surveillance (AS). Patients and Methods We identified men in Michigan initially diagnosed with GG1 prostate cancer, from January 2012 to November 2017, who had a RP within 1 year of diagnosis. Our endpoints were: (i) ≥GG2 cancer at RP and (ii) adverse pathology (≥GG3 and/or ≥pT3a). We compared upgrading according to NCCN risk, number of positive biopsy cores, and age. Last, we examined if confirmatory test results were associated with upgrading or adverse pathology at RP. Results Amongst 1966 patients with GG1 cancer at diagnosis, the rates of upgrading to ≥GG2 and adverse pathology were 40% and 59% (P< 0.001), and 10% and 17% (P= 0.003) for patients with very-low-and low-risk cancers, respectively. Upgrading by volume ranged from 49% to 67% for ≥GG2, and 16% to 23% for adverse pathology. Generally, more patients aged ≥70 vs <70 years had adverse pathology. Unreassuring confirmatory test results had a higher likelihood of adverse pathology than reassuring tests (35% vs 18%, P= 0.017). Conclusions Upgrading and adverse pathology are common amongst patients initially diagnosed with GG1 prostate cancer. Early use of confirmatory testing may facilitate the identification of patients with more aggressive disease ensuring improved risk classification and safer selection of patients for AS.

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“…A recently published study of a cohort of 296 men with very low-risk (37.8% ) or low-risk (62.2%) disease who underwent GPS testing found that GPS score did not differ significantly across quartiles of disease volume (defined as percent of positive cores, number of cores with > 50% involvement, largest involvement of any single core, and PSA density) [13]. However, the median likelihood of favorable pathology at RP was statistically different between volume quartiles.…”

Section: Prediction Of Disease Progression In Active Surveillancementioning

confidence: 99%

The Clinical Applications of Tissue Biomarkers in Prostate Cancer

Lonergan¹,

Washington²,

Meng³

et al. 2020

Société Internationale D’Urologie Journal

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The clinical course of localized prostate cancer varies widely, from indolent disease unlikely to need treatment to aggressive disease requiring intensive, multimodal therapy. Traditionally, treatment decisions have been based on clinical and pathologic factors, including serum prostate specific antigen (PSA), clinical stage, and Gleason score. However, these factors have limited ability to describe the underlying tumor biology. Tissue-based genomic tests have emerged as a promising tool to more accurately characterize prostate cancer biology and predict clinical course. Using prostate cancer tissue obtained at pre-treatment biopsy or radical prostatectomy, these tests exploit the expression of specific genes involved in key biological pathways and, as a result, have the potential to aid clinical decision-making. The current review summarizes available data describing the clinical use of 5 commercially available tissue-based genomic assays in a number of clinical scenarios.

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Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance

Cited by 12 publications

References 30 publications

Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category

Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category

Pathological upgrading at radical prostatectomy for patients with Grade Group 1 prostate cancer: implications of confirmatory testing for patients considering active surveillance

The Clinical Applications of Tissue Biomarkers in Prostate Cancer

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