Assessment of Oncological Outcomes After Radical Prostatectomy According to Preoperative and Postoperative Cancer of the Prostate Risk Assessment Scores: Results from a Large, Two-center Experience

Leyh-Bannurah, Sami-Ramzi; Dell’Oglio, Paolo; Zaffuto, Emanuele; Briganti, Alberto; Schiffmann, Jonas; Pompe, Raisa S.; Tilki, Derya; Heinzer, Hans; Graefen, Markus; Karakiewicz, Pierre I.; Budäus, Lars

doi:10.1016/j.euf.2017.10.015

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…Prostate cancer (PC) is the second most common cancer in men worldwide [1]. After primary radical prostatectomy (RP), the recurrence rate ranges between 7 and 50% within 5 years after surgery [2,3]. In these cases, early detection and localization of recurrent disease is crucial for further disease management [4,5].…”

Section: Introductionmentioning

confidence: 99%

Pre-test 68Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy—validation of a prediction model

et al. 2020

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Objectives: The aim of this study was the validation of a recently established comprehensive and compact prediction model for 68 Ga-PSMA-11-ligand positron-emission tomography (PET) positivity with an independent subsequent patient series. Methods: A total of 292 consecutive patients with early biochemical recurrence after radical prostatectomy and PSA values between 0.2 and 1 ng/ml who underwent 68 Ga-PSMA-11-ligand PET/computed tomography (CT) between January 2016 and June 2017 were retrospectively included. The cohort was divided into a very low PSA value (0.2-0.5 ng/ml, n = 151) and a low PSA value (> 0.5-1 ng/ml, n = 141) subgroup. First, pre-test positivity probabilities for each patient were calculated according to the previously published comprehensive prediction model using all clinical variables (PSA value, ISUP grade group, T-and N-stage, patient under androgen deprivation therapy (ADT), previous radiation therapy) and the compact model using just the most predictive factors PSA value, ADT, and grade group. Then, all 68 Ga-PSMA-11-ligand PET/CTs were analysed by one experienced nuclear medicine physician, and the results were correlated to the calculated pre-test probabilities. Results: In the very low PSA value subgroup, mean pre-test probability for positive findings in 68 Ga-PSMA-11-ligand PET/CT was 57% (95% CI 55-60%) according to the compact model and 59% (95% CI 56-61%) according to the comprehensive model. In the low PSA value subgroup, mean pre-test probability was 72% (95% CI 70-74%) in the compact model and 74% (95% CI 72-76%) in the comprehensive model. After image analysis, 59% (89/151) of the patients in the very low PSA value subgroup revealed positive imaging findings. Seventy-nine percent (112/141) of the patients in the low PSA value subgroup presented with positive findings in the 68 Ga-PSMA-11-ligand PET/CT. The accuracy (AUC) of the prediction models was 0.71 (95% CI 0.65-0.78) for the compact model and 0.74 (95% CI 0.68-0.80) for the comprehensive model.

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Section: Introductionmentioning

confidence: 99%

Pre-test 68Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy—validation of a prediction model

et al. 2020

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“…Although statistically significant differences in BCR rates between the three different CAPRA-S risk groups have been validated in multiple cohorts [ 5 – 8 , 20 , 21 ], heterogeneity of clinical outcome is still observed among the high-risk CAPRA-S group. As such, while some patients with high-risk CAPRA-S scores may benefit from multimodal therapy up-front, a proportion of these high-risk patients will not go on to develop BCR or metastasis, and will experience unnecessary morbidity from early treatment [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

A 38-gene model comprised of key TET2-associated genes shows additive utility to high-risk prostate cancer cases in the prognostication of biochemical recurrence

2020

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Background Early treatment of patients at risk for developing aggressive prostate cancer is able to delay metastasis and reduce mortality; as such, up-front identification of these patients is critical. Several risk classification systems, including CAPRA-S, are currently used for disease prognostication. However, high-risk patients identified by these systems can still exhibit wide-ranging disease outcomes, leading to overtreatment of some patients in this group. Methods The master methylation regulator TET2 is downregulated in prostate cancer, where its loss is linked to aggressive disease and poor outcome. Using a random forest strategy, we developed a model based on the expression of 38 genes associated with TET2 utilizing 100 radical prostatectomy samples (training cohort) with a 49% biochemical recurrence rate. This 38-gene model was comprised of both upregulated and downregulated TET2-associated genes with a binary outcome, and was further assessed in an independent validation (n = 423) dataset for association with biochemical recurrence. Results 38-gene model status was able to correctly identify patients exhibiting recurrence with 81.4% sensitivity in the validation cohort, and added significant prognostic utility to the high-risk CAPRA-S classification group. Patients considered high-risk by CAPRA-S with negative 38-gene model status exhibited no statistically significant difference in time to recurrence from low-risk CAPRA-S patients, indicating that the expression of TET2-associated genes is able to separate truly high-risk cases from those which have a more benign disease course. Conclusions The 38-gene model may hold potential in determining which patients would truly benefit from aggressive treatment course, demonstrating a novel role for genes linked to TET2 in the prognostication of PCa and indicating the importance of TET2 dysregulation among high-risk patient groups.

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“…Notably, downregulation of CXCL4L1 was significantly associated with high CAPRA score, which usually predicts unfavorable clinical outcomes for PCa patients. The CAPRA score system, first established by the University of California, San Francisco (UCSF) in 2005, has been recognized as a powerful predictive tool and validated in multiple surgical cohorts 1127. Krishnan et al 28.…”

Section: Discussionmentioning

confidence: 99%

“…The median follow-up duration was 45 (range: 6–84) months. For disease progression, BCR was defined as two sequential PSA values ≥0.2 ng ml −1 after prostatectomy 11. The development of CRPC was judged according to the European Association of Urology (EAU) guidelines 12.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of serum CXCL4L1 predicts progression and poor prognosis in prostate cancer patients treated by radical prostatectomy

et al. 2019

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Our previous study found that plate factor-4 variant (CXCL4L1) was downregulated in the serum of patients with prostate cancer (PCa). The aim of the present study was to investigate the prognostic value of CXCL4L1 in PCa. In total, 213 PCa patients treated with radical prostatectomy were enrolled and peripheral blood samples of all patients were collected. Expression of serum CXCL4L1 in patients with different tumor stages and grades were measured by enzyme-linked immunosorbent assay (ELISA). The Kaplan–Meier method was applied to estimate the progression to castration-resistant prostate cancer (CRPC), metastasis, biochemical recurrence (BCR)-free survival, and overall survival (OS). Prognostic factors for BCR-free survival and OS were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. The expression of CXCL4L1 was significantly lower in PCa patients with advanced pathological tumor stage, high-grade Gleason score, and metastasis. Moreover, downregulation of CXCL4L1 not only strongly correlated with aggressive clinicopathological features, but also predicted tumor progression and unfavorable outcomes. Finally, multivariate Cox regression analyses identified CXCL4L1 as an independent prognostic factor for both BCR-free survival (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.26–3.27; P = 0.004) and OS (HR: 2.26, 95% CI: 1.07–4.79; P = 0.033). In conclusion, our results indicate that CXCL4L1 might serve as a novel and promising prognostic biomarker for patients with PCa and potential therapeutic target in the future.

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Assessment of Oncological Outcomes After Radical Prostatectomy According to Preoperative and Postoperative Cancer of the Prostate Risk Assessment Scores: Results from a Large, Two-center Experience

Cited by 6 publications

References 31 publications

Pre-test 68Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy—validation of a prediction model

Pre-test 68Ga-PSMA-ligand PET/CT positivity in early biochemical recurrent prostate cancer after radical prostatectomy—validation of a prediction model

A 38-gene model comprised of key TET2-associated genes shows additive utility to high-risk prostate cancer cases in the prognostication of biochemical recurrence

Downregulation of serum CXCL4L1 predicts progression and poor prognosis in prostate cancer patients treated by radical prostatectomy

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