Modern paradigms for prostate cancer detection and management

Williams, Isabella; McVey, Aoife; Perera, Sachin; O’Brien, J; Kostos, Louise; Chen, Kenneth; Azad, Arun; Murphy, Declan; Kasivisvanathan, Veeru; Lawrentschuk, Nathan; Frydenberg, Mark

doi:10.5694/mja2.51722

Cited by 48 publications

(21 citation statements)

References 88 publications

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“…Currently, prostate biopsy continues to be regarded as the definitive method for confirming the diagnosis of PCa. 21 A variety of noninvasive diagnosis have been explored due to concerns about over-detection of low-risk cancers and the risk of missing clinically significant cancers as well as risk of infections. 17 particularly in patients whose PSA levels fall within the gray zone.…”

Section: Discussionmentioning

confidence: 99%

Based on PI‐RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4−20 ng/mL

Huang,

Liu,

et al. 2023

The Prostate

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PurposeThe study aimed to investigate the diagnostic accuracy of prostate health index (PHI) and apparent diffusion coefficient (ADC) values in predicting prostate cancer (PCa) and construct a nomogram for the prediction of PCa and clinically significant PCa (CSPCa) in Prostate Imaging‐Reporting and Data System (PI‐RADS) three lesions cohort.MethodsThis study prospectively enrolled 301 patients who underwent multiparametric magnetic resonance (mpMRI) and were scheduled for prostate biopsy. The receiver operating characteristic curve (ROC) was performed to estimate the diagnostic accuracy of each predictor. Univariable and multivariable logistic regression analysis was conducted to ascertain hidden risk factors and constructed nomograms in PI‐RADS three lesions cohort.ResultsIn the whole cohort, the area under the ROC curve (AUC) of PHI is relatively high, which is 0.779. As radiographic parameters, the AUC of PI‐RADS and ADC values was 0.702 and 0.756, respectively. The utilization of PHI and ADC values either individually or in combination significantly improved the diagnostic accuracy of the basic model. In PI‐RADS three lesions cohort, the AUC for PCa was 0.817 in the training cohort and 0.904 in the validation cohort. The AUC for CSPCa was 0.856 in the training cohort and 0.871 in the validation cohort. When applying the nomogram for predicting PCa, 50.0% of biopsies could be saved, supplemented by 6.9% of CSPCa being missed.ConclusionPHI and ADC values can be used as predictors of CSPCa. The nomogram included PHI, ADC values and other clinical predictors demonstrated an enhanced capability in detecting PCa and CSPCa within PI‐RADS three lesions cohort.

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Section: Discussionmentioning

confidence: 99%

Based on PI‐RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4−20 ng/mL

Huang,

Liu,

et al. 2023

The Prostate

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show abstract

“…In the USA, a PSA level > 4.0 ng/ml was considered as the threshold that reference to prostate biopsy; however, PSA is not cancer-specific and elevated PSA levels can be owing to benign prostatic hyperplasia (BPH) and prostatitis 5 . Therefore, PSA demonstrates high sensitivity but low specificity, which may result in overdiagnosis and treatment of indolent prostate lesions 6 . Additionally, only 20.4% of men PSA level of 4–10 ng/ml were diagnosed with csPCa, which is called the gray zone 7 .…”

Section: Introductionmentioning

confidence: 99%

PI-RADS v2.1 and PSAD for the prediction of clinically significant prostate cancer among patients with PSA levels of 4–10 ng/ml

Wen,

Liu,

Shen

et al. 2024

Sci Rep

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This study intended to evaluate the diagnostic accuracy of the prostate imaging reporting and data system (PI-RADS) and prostate-specific antigen density (PSAD) for clinically significant prostate cancer (csPCa) with PSA levels of 4–10 ng/ml. Between July 2018 and June 2022, a total of 453 patients with PSA levels of 4–10 ng/ml were retrospectively included, which were randomly assigned to the training group (323 patients) and validation group (130 patients). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with their 95% CI were calculated. The overall diagnostic performance was determined with area under the receiver operating characteristic curve (AUC), and an integrated nomogram combining PI-RADS score and PSAD was constructed and tested in a validation cohort. In the training group, the AUC for PI-RADS 2.1 and PSAD alone were 0.875 (95% CI 0.834–0.916) and 0.712 (95% CI 0.648–0.775). At the cutoff PI-RADS score ≥ 4, the sensitivity and specificity were 86.2% (95% CI 77.4–1.9%) and 84.7% (95% CI 79.6–88.8%), respectively. For PSAD, the sensitivity and specificity were 73.3% (95% CI 63.0–82.4%) and 62.1% (95% CI 55.8–68.5%) at the cutoff 0.162 ng/ml/ml. While combining PI-RADS with PSAD, the diagnostic performance was improved significantly, with AUC of 0.893 (95% CI 0.853–0.933). In the validation group, the nomogram yielded a AUC of 0.871 (95% CI 0.807–0.934), which is significantly higher than PI-RADS alone (0.829, 95% CI 0.759–0.899, P = 0.02). For patients with PSA levels of 4–10 ng/ml, PSAD demonstrated moderate diagnostic accuracy whereas PI-RADS showed high performance. By combination of PSAD and PI-RADS together, the diagnostic performance could be improved significantly.

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“…Furthermore, despite widespread use, the sensitivity of PSA for diagnosing PCa is also insufficient 9 . Currently, PSA is coupled with prostate biopsy 10 . the gold standard of PCa diagnosis that can confirm cancer presence and identify its stage.…”

Section: Introductionmentioning

confidence: 99%

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

Zhang,

Yu,

Bai

et al. 2024

J. Cancer

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Bicalutamide (BIC) resistance impedes the treatment of prostate cancer (PCa) and seems to involve ferroptosis; however, the underlying mechanism remains unclear. Our study aimed to explore how miR-15b-3p modulates ferroptosis in response to BIC resistance and determine whether the miRNA is suitable for early screening of PCa. Here, we found that PCa tissues had significantly higher miR-15b-3p expression than adjacent normal tissues. Analysis of blood samples in patients who underwent prostate-specific antigen (PSA) screening revealed that miR-15b-3p was a more accurate diagnostic than PSA (miR-15b-3p area under the curve [AUC] = 0.941, PSA AUC = 0.815). In vitro experiments then demonstrated that miR-15b-3p expression was markedly higher in LNCaP, PC-3, and DU145 cells than in RWPE-1 cells. Treatment with BIC decreased miR-15b-3p expression and progressive ferroptosis. Mechanistically, we identified KLF2 as the downstream target of miR-15b-3p. Overexpressing KLF2 facilitated ferroptosis via augmenting MDA and iron concentrations, in turn inhibiting the SLC7A11/GPX4 axis and decreasing GSH concentration. Through modulating ferroptosis, miR-15b-3p mimic and inhibitor weakened and enhanced BIC sensitivity, respectively. Furthermore, BIC treatment limited xenograft tumor volume in vivo, whereas agomir-15b-3p promoted tumor growth, indicating that miR-15b-3p attenuated the tumor-suppressive effects of BIC. Taken together, our results suggested that miR-15b-3p is crucial to BIC resistance, specifically via targeting KLF2 and thereby suppressing ferroptosis. High miR-15b-3p expression in early PCa screening should reflect a higher probability of cancer. In conclusion, miR-15b-3p has strong potential as a screening and diagnostic biomarker with reliable prospects for clinical application. Furthermore, because patients with high miR-15b-3p and low KLF2 expression have a greater risk of BIC resistance and malignant progression, targeting the miRNA and its downstream protein may be a new treatment strategy.

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Modern paradigms for prostate cancer detection and management

Abstract: Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials.

Cited by 48 publications

References 88 publications

Based on PI‐RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4−20 ng/mL

Based on PI‐RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4−20 ng/mL

PI-RADS v2.1 and PSAD for the prediction of clinically significant prostate cancer among patients with PSA levels of 4–10 ng/ml

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

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