Heterogeneity of Outcomes in D'Amico Intermediate-Risk Prostate Cancer Patients after Radical Prostatectomy: Influence of Primary and Secondary Gleason Score

Pollard, Matthew; Hobbs, Adele R.; Kwon, Young Suk; Katsigeorgis, Maria; Lavery, Hugh J.; Levinson, Adam W.; Bernstein, Adrien; Collingwood, Shemille A.; Hall, Simon; Jazayeri, Seyed Behzad; Samadi, David B.

doi:10.1159/000477545

Cited by 3 publications

(4 citation statements)

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“…The widely accepted D'Amico score 17 has been challenged as an optimal risk stratification tool 18 . Clinical outcomes after RP of PCa patients in the intermediate‐risk group according to D'Amico demonstrate significant heterogeneity, 19 suggesting that a subset of these patients has indolent cancer and may benefit from conservative management such as AS. The UCSF‐CAPRA score has distinct advantages regarding risk stratification compared to the D'Amico score 20,21 .…”

Section: Discussionmentioning

confidence: 99%

Validation of the prognostic value of a three‐gene signature and clinical parameters‐based risk score in prostate cancer patients

Saemundsson

Xu²,

Meisgen³

et al. 2023

The Prostate

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Background The study aimed to validate the prognostic value of the Prostatype® risk score (P‐score), which includes a three‐gene signature and conventional risk factors, in a retrospective cohort. Methods All 716 patients diagnosed with prostate cancer from 2008 to 2010 at Skåne University Hospital, Sweden, were included. After excluding patients based on pathological and clinical eligibility criteria, RNA quality, and presence of metastases at diagnosis, a final cohort comprising 316 patients was further analyzed. Expression levels of three genes (IGFBP3, F3, and VGLL3) were measured in archived formalin‐fixed paraffin‐embedded core needle biopsies. The gene expression data were combined with clinical parameters (Gleason score, prostate‐specific antigen, and clinical tumor stage) to calculate the P‐score for each patient. Predictive performance of the P‐score in terms of prostate cancer‐specific mortality (PCSM), distant metastasis and adverse pathological outcomes were investigated. Results The P‐score predicted both PCSM (hazard ratio [HR] = 1.6) and metastasis (HR = 1.46). The P‐score had an area under curve (AUC) of 0.93 when predicting the PCSM risk at 10 years (95% confidence interval [CI]: 0.89–0.98), which was significantly better than both D'Amico (AUC: 0.81, 95% CI: 0.72–0.90, p < 0.001) and UCSF‐CAPRA (AUC: 0.88, 95% CI: 0.80–0.96, p < 0.05). Decision curve analysis showed a higher net benefit of the P‐score compared to both D'Amico and CAPRA. All three risk scores performed similarly in the prediction of distant metastases. For patients who underwent radical prostatectomy (RP), a higher P‐score correlated with adverse pathological features such as pathologic tumor stage T3‐4 (p < 0.0001) and ≥International Society of Urological Pathology grade group 3 (p < 0.0001). Conclusions Our findings provide evidence for the prognostic value of the P‐score. The P‐score predicted the risk for PCSM more accurately than the D'Amico and CAPRA scores. Performance was similar when predicting the risk for development of distant metastases within 10 years. Moreover, the P‐score correlated with adverse pathological outcomes in RP specimens. Thus, the P‐score could provide useful information for patients and their doctors to make informed decisions at the time of diagnosis.

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Section: Discussionmentioning

confidence: 99%

Validation of the prognostic value of a three‐gene signature and clinical parameters‐based risk score in prostate cancer patients

Saemundsson

Xu²,

Meisgen³

et al. 2023

The Prostate

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“…This suggests that a subset of patients in this intermediate risk category harbor indolent tumors, causing uncertainty about the necessity of radical interventions. 10 Similarly, heterogeneous outcomes among patients assigned to the intermediate risk group according to the National Comprehensive Cancer Network (NCCN) guidelines have been reported, 11 although this has been improved by subdividing patients into favorable and unfavorable intermediate risk groups. 4 , 12 Nevertheless, more reliable risk stratification systems are needed to guide decision-making and to avoid overtreatment of patients with clinically insignificant lesions while ensuring adequate therapeutic intervention for those with aggressive tumors.…”

Section: Introductionmentioning

confidence: 99%

A Novel Risk Score (P-score) Based on a Three-Gene Signature, for Estimating the Risk of Prostate Cancer-Specific Mortality

Söderdahl¹,

Xu²,

Bring³

et al. 2022

RRU

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Purpose To develop and validate a risk score (P-score) algorithm which includes previously described three-gene signature and clinicopathological parameters to predict the risk of death from prostate cancer (PCa) in a retrospective cohort. Patients and Methods A total of 591 PCa patients diagnosed between 2003 and 2008 in Stockholm, Sweden, with a median clinical follow-up time of 7.6 years (1–11 years) were included in this study. Expression of a three-gene signature (IGFBP3, F3, VGLL3) was measured in formalin-fixed paraffin-embedded material from diagnostic core needle biopsies (CNB) of these patients. A point-based scoring system based on a Fine-Gray competing risk model was used to establish the P-score based on the three-gene signature combined with PSA value, Gleason score and tumor stage at diagnosis. The endpoint was PCa-specific mortality, while other causes of death were treated as a competing risk. Out of the 591 patients, 315 patients (estimation cohort) were selected to develop the P-score. The P-score was subsequently validated in an independent validation cohort of 276 patients. Results The P-score was established ranging from the integers 0 to 15. Each one-unit increase was associated with a hazard ratio of 1.39 (95% confidence interval: 1.27–1.51, p < 0.001). The P-score was validated and performed better in predicting PCa-specific mortality than both D’Amico (0.76 vs 0.70) and NCCN (0.76 vs 0.71) by using the concordance index for competing risk. Similar improvement patterns are shown by time-dependent area under the curve. As demonstrated by cumulative incidence function, both P-score and gene signature stratified PCa patients into significantly different risk groups. Conclusion We developed the P-score, a risk stratification system for newly diagnosed PCa patients by integrating a three-gene signature measured in CNB tissue. The P-score could provide valuable decision support to distinguish PCa patients with favorable and unfavorable outcomes and hence improve treatment decisions.

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“…3D telomere profiling as utilized in this report, has previously been applied to other cancers, including neuroblastoma, glioblastoma, myelodysplastic syndromes and acute myeloid leukemia, Hodgkin’s lymphoma, multiple myeloma, and thyroid cancer [8,9,10,11,12,13]. In all cases examined so far, this technology was able to identify patient subgroups.…”

Section: Discussionmentioning

confidence: 99%

“…The apparent paradox in clinical prognostic grouping of patients and the inter- and intra-personal differences between patients of the same pathology grouping is linked to the level of genomic instability present in the patient’s tumor: More genomic instability in individual tumor cells sets the stage for ongoing tumor cell (micro)evolution and leads to the generation of several subsets of tumor cells with distinct genetic properties. These genetic variants contribute to tumor development and progression [1,2,3,4,5,8,9].…”

Section: Introductionmentioning

confidence: 99%

Advancing Risk Assessment of Intermediate Risk Prostate Cancer Patients

Drachenberg

Awe

Pozzo

et al. 2019

Cancers

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The individual risk to progression is unclear for intermediate risk prostate cancer patients. To assess their risk to progression, we examined the level of genomic instability in circulating tumor cells (CTCs) using quantitative three-dimensional (3D) telomere analysis. Data of CTCs from 65 treatment-naïve patients with biopsy-confirmed D’Amico-defined intermediate risk prostate cancer were compared to radical prostatectomy pathology results, which provided a clinical endpoint to the study and confirmed pre-operative pathology or demonstrated upgrading. Hierarchical centroid cluster analysis of 3D pre-operative CTC telomere profiling placed the patients into three subgroups with different potential risk of aggressive disease. Logistic regression modeling of the risk of progression estimated odds ratios with 95% confidence interval (CI) and separated patients into “stable” vs. “risk of aggressive” disease. The receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.77, while prostate specific antigen (PSA) (AUC of 0.59) and Gleason 3 + 4 = 7 vs. 4 + 3 = 7 (p > 0.6) were unable to predict progressive or stable disease. The data suggest that quantitative 3D telomere profiling of CTCs may be a potential tool for assessing a patient’s prostate cancer pre-treatment risk.

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Heterogeneity of Outcomes in D'Amico Intermediate-Risk Prostate Cancer Patients after Radical Prostatectomy: Influence of Primary and Secondary Gleason Score

Cited by 3 publications

References 40 publications

Validation of the prognostic value of a three‐gene signature and clinical parameters‐based risk score in prostate cancer patients

Validation of the prognostic value of a three‐gene signature and clinical parameters‐based risk score in prostate cancer patients

A Novel Risk Score (P-score) Based on a Three-Gene Signature, for Estimating the Risk of Prostate Cancer-Specific Mortality

Advancing Risk Assessment of Intermediate Risk Prostate Cancer Patients

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