Recent Progress and Upcoming Paths: Current Developments in Chemotherapy for Metastatic Prostate Cancer Treatment

Magnetic Resonance Imaging/Ultrasound Fusion Guided Prostate Biopsy Improves Cancer Detection Following Transrectal Ultrasound Biopsy and Correlates With Multiparametric Magnetic Resonance Imaging

Multiparametric 3T Prostate Magnetic Resonance Imaging to Detect Cancer: Histopathological Correlation Using Prostatectomy Specimens Processed in Customized Magnetic Resonance Imaging Based Molds

Prostate MRI: Who, when, and how? Report from a UK consensus meeting

Objective The aim of the study is to compare the diagnostic value of multiparametric transrectal ultrasound(TRUS) and multiparametric magnetic resonance imaging (MRI) in prostate cancer. Methods The clinical data of 102 patients who received multiparametric TRUS (including conventional transrectal ultrasound, shear wave sonoelastography and contrast enhanced ultrasound), multiparametric MRI(including T2 weighted diffusion weighted, and dynamic contrast enhanced MRI) and laboratory tests from April 2016 to May 2018 were retrospectively analyzed. The average age was 66.1 years old, ranging 38.0-85.0 years old. The average PSA was 30.1 ng/ml, ranging 0.4-227.0 ng/ml. The average PSAD was 0.67 ng/ml2, ranging 0.02-4.27 ng/ml2. The pathology results from TRUS guided biopsy or surgical operation were chosen as gold standard. Diagnostic performance including sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV), accuracy and area under the receiver operating characteristic curve(AUROC)of multiparametric TRUS and multiparametric MRI in prostate cancer were analyzed. Results There were 62 prostate cancer and 40 BPH patients in our study. Parallel multiparametric TRUS diagnosed 63 prostate cancer and 39 BPH, and multiparametric MRI diagnosed 75 prostate cancer and 27 BPH. The sensitivity, specificity and accuracy of parallel multiparametric TRUS were 98.4%, 70.0% and 87.3%, respectively. And those of multiparametric MRI were 95.2%, 60.0% and 81.4%, respectively. The AUROC of parallel multiparametric TRUS and multiparametric MRI were 0.842 and 0.776, with no significant differences(P=0.208). Conclusion The diagnostic value of multiparametric TRUS was not inferior to multiparametric MRI in prostate cancer. Key words: Prostatic neoplasms; Prostate cancer; Magnetic resonance imaging; Transrectal ultrasound; Multiparametric

Nursing and Residential CareVol. 17, No. 3 EditorialCancer treatment: at what cost?Beverley AndersonBeverley AndersonSearch for more papers by this authorBeverley AndersonPublished Online:18 Feb 2015https://doi.org/10.12968/nrec.2015.17.3.173AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Aapro MS (2012) Management of advanced prostate cancer in senior adults: the new landscape. Oncologist 17(Suppl 1): 16–22 Crossref, Google ScholarAttard G, Reid AHM, Yap TA et al. (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. 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Background Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/MRI may improve detection of clinically significant prostate cancer (CSPC). Purpose To compare the sensitivity and specificity of 68Ga-PSMA PET/MRI with multiparametric MRI for detecting CSPC. Materials and Methods Men with prostate specific antigen levels of 2.5-20 ng/mL prospectively underwent 68Ga-PSMA PET/MRI, including multiparametric MRI sequences, between June 2019 and March 2020. Imaging was evaluated independently by two radiologists by using the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. Sensitivity and specificity for CSPC (International Society of Urological Pathology grade group ≥ 2) were compared for 68Ga-PSMA PET/MRI and multiparametric MRI by using the McNemar test. Decision curve analysis compared the net benefit of each imaging strategy. Results Ninety-nine men (median age, 67 years; interquartile range, 62-71 years) were included; 79% (78 of 99) underwent biopsy. CSPC was detected in 32% (25 of 78). For CSPC, specificity was higher for 68Ga-PSMA PET/MRI than multiparametric MRI (76% [95% CI: 62, 86] vs 49% [95% CI: 35, 63], respectively; P < .001). Sensitivity was similar (88% [95% CI: 69, 98] vs 92% [95% CI: 74, 99], respectively; P > .99). For PI-RADS 3 lesions, specificity was also higher for 68Ga-PSMA PET/MRI than for multiparametric MRI: 86% (95% CI: 73, 95) versus 59% (95% CI: 43, 74), respectively (P = .002). Decision curve analysis showed that biopsies targeted to PSMA uptake increased the net benefit of multiparametric MRI only among PI-RADS 3 lesions. The net benefit of targeted biopsy for a PI-RADS 3 lesion with PSMA uptake was higher across all threshold probabilities over 8%. The net benefit of targeted biopsy was similar for PI-RADS 4 and 5 lesions, regardless of PSMA uptake. Conclusions Gallium 68 prostate-specific membrane antigen PET/MRI improved specificity for clinically significant prostate cancer compared with multiparametric MRI, particularly in Prostate Imaging Reporting and Data System grade 3 lesions. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Williams and Estes in this issue.

COMPLETE ANDROGEN BLOCKADE FOR PROSTATE CANCER: WHAT WENT WRONG?

Characterizing Clinically Significant Prostate Cancer Using Template Prostate Mapping Biopsy

Prostate Cancer Diagnosis on Repeat Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy of Benign Lesions: Recommendations for Repeat Sampling

Development of neuroendocrine prostate cancer (NEPC) is emerging as a major problem in clinical management of advanced prostate cancer (PCa). As increasingly potent androgen receptor (AR)‐targeting antiandrogens are more widely used, PCa transdifferentiation into AR‐independent NEPC as a mechanism of treatment resistance becomes more common and precarious, since NEPC is a lethal PCa subtype urgently requiring effective therapy. Reprogrammed glucose metabolism of cancers, that is elevated aerobic glycolysis involving increased lactic acid production/secretion, plays a key role in multiple cancer‐promoting processes and has been implicated in therapeutics development. Here, we examined NEPC glucose metabolism using our unique panel of patient‐derived xenograft PCa models and patient tumors. By calculating metabolic pathway scores using gene expression data, we found that elevated glycolysis coupled to increased lactic acid production/secretion is an important metabolic feature of NEPC. Specific inhibition of expression of MCT4 (a plasma membrane lactic acid transporter) by antisense oligonucleotides led to reduced lactic acid secretion as well as reduced glucose metabolism and NEPC cell proliferation. Taken together, our results indicate that elevated glycolysis coupled to excessive MCT4‐mediated lactic acid secretion is clinically relevant and functionally important to NEPC. Inhibition of MCT4 expression appears to be a promising therapeutic strategy for NEPC.

To review current prostate-specific antigen (PSA) metrics used in monitoring treatment of advanced prostate cancer, with a specific focus on castration-resistant prostate cancer (CRPC) therapies. Explore what is known about the correlation between PSA and androgen levels as well as underlying reasons for persistent PSA expression and serum elevation in CRPC, and outline suggestions for use of PSA in managing patients with advanced prostate cancer. A comprehensive search of the PubMed database for English language articles through April 2012 was performed using the following Medical Subject Headings (MeSH) keywords or terms, alone or in combination: 'prostate cancer'; 'prostate cancer treatment'; 'prostate cancer outcomes'; 'prostate-specific antigen'; 'androgen receptor'; 'advanced prostate cancer'; 'castration-resistant prostate cancer'; 'biomarkers'. Bibliographies of relevant articles were searched for additional references. Relevant medical society and regulatory agency web sites from the USA and Europe were accessed for issued guidance on PSA use. PSA doubling time (PSADT) is a useful metric for determining which patients should be considered for androgen-deprivation therapy (ADT) after failing local treatment or for second-line therapies after failing ADT. However, it is not a validated surrogate for survival and no therapy has received regulatory approval based upon PSADT characteristics. PSA nadir and time-to-nadir have been identified as possible prognostic markers for patients receiving ADT. There is no universally accepted definition for PSA progression, nor is PSA progression a regulatory-approved surrogate for clinical progression in drug approval trials. PSA responses to second-line therapies can vary and are not considered by regulatory agencies as valid surrogates for clinical endpoints, so they must be assessed in the context of each individual therapy and trial design. PSA expression in CRPC is often a reflection of persistent androgen receptor activity. While we can provide guidance for use of PSA monitoring in managing patients with advanced prostate cancer based on the data at hand, there is an urgent need for prospective analyses of refined PSA metrics in conjunction with newer prostate cancer biomarkers in clinical trials to provide stronger evidence for their roles as surrogate endpoints.

Prostate cancer is the most commonly diagnosed malignancy in men and continues to be a leading cause of cancer-related mortality. Accurate and timely diagnosis is essential for distinguishing clinically significant tumors from indolent lesions and for informing treatment decisions. Multiparametric magnetic resonance imaging (mpMRI) has revolutionized prostate cancer detection by enabling precise lesion localization, risk stratification, and improved biopsy targeting. Fusion biopsy, which combines mpMRI findings with real-time transrectal ultrasonography (TRUS), has emerged as a highly effective method for sampling suspicious lesions. This review provides an integrated anatomical, epidemiological, technical, and clinical overview that highlights the evolving role of fusion biopsy in contemporary prostate cancer diagnostics. We also explore emerging strategies such as penumbra-targeted sampling, discuss ongoing clinical challenges, and examine the impact of biopsy underestimation and lack of standardization. Compared to conventional systematic biopsy, mpMRI-TRUS fusion biopsy improves the detection of clinically significant prostate cancer while reducing the overdiagnosis of low-risk tumors. To our knowledge, few recent reviews have comprehensively synthesized current clinical guidelines, emerging biopsy techniques, and future directions within a single narrative. mpMRI-TRUS-guided fusion biopsy represents a major advancement in the prostate cancer diagnostic pathway, promoting precision oncology by reducing overtreatment and facilitating individualized patient care. This review aims to assist clinicians in adopting biopsy innovations that enhance diagnostic accuracy and improve patient outcomes.

Point-Counterpoint: Radioisotope-guided Lymphadenectomy for Pelvic Node Staging: The SENTINELLE Study.

Purpose: In this study, we aimed to study whether 5-hydroxymethylcytosine sequencing (5hmC-seq) of circulating cell-free DNA (cfDNA) predicts gene expression in tumor tissue and can distinguish tumor subtypes defined in tissue in metastatic castration-resistant prostate cancer (mCRPC). Methods: We performed 5hmC-seq on cfDNA samples from 86 mCRPC patients with matched tumor tissue profiled with 5hmC-seq (N=49) and RNA-sequencing (N=86) and we compared cfDNA 5hmC levels with matched tissue 5hmC levels and tissue gene expression. We developed a 5hmC-seq-based circulating tumor-DNA fraction (ctDNA-fraction) classifier and assessed if gene-level and pathway-level differences between mCRPC subtypes could be detected in cfDNA using a differential 5hmC-analysis adjusting for ctDNA-fraction. Results: Patients with androgen receptor (AR)-positive prostate cancer (ARPC) exhibited lower ctDNA-fraction, whereas patients with neuroendocrine (NE) prostate cancer (NEPC) and double-negative prostate cancer (DNPC) tumors displayed higher ctDNA-fraction (median ctDNA-fraction across subtypes 0.09 [95% confidence interval (CI), 0.04-0.14] (ARPC), 0.41 [95% CI, 0.18-0.64] (NEPC) and 0.37 [95% CI, 0.30-0.44] (DNPC), pairwise t-test P = 5.5 x 10-2 (ARPC vs. NEPC) and P = 8.8 x 10-4 (ARPC vs. DNPC) respectively). Nearly 30% of all protein-coding genes showed significant concordance between cfDNA 5hmC and tissue RNA-seq, after adjusting for ctDNA-fraction (adjusted p&amp;lt;0.05 in linear model), which were enriched in the androgen response, EGFR, and ERBB signaling pathways. Compared to ARPC, NEPC displayed upregulated 5hmC enrichment in NE-related genes, and downregulated androgen response and MYC target pathways in cfDNA. As expected, an NE pathway score calculated from cfDNA 5hmC was significantly different between tissue-confirmed ARPC and NEPC (p=0.03). Double-negative prostate cancer (DNPC) showed downregulated androgen response and MYC targets and upregulated epithelial cell pathways compared to ARPC in cfDNA. Furthermore, DNPC indicated an aggressive phenotype with cell proliferation pathways even more upregulated when compared to NEPC. Conclusions: We created a cohort of 86 matched tissue and cfDNA samples and demonstrated concordance for a significant number of transcribed protein-coding genes. Expected biological differences previously seen in tissue between NEPC and ARPC were readily detected via 5hmC profiles in cfDNA. Furthermore, DNPC showed a clear downregulation of androgen response signaling in cfDNA, indicating the possibility to identify a group of patients in addition to classical NEPC that may have reduced response to standard androgen-targeting agents. Future work will aim to develop single-sample multi-class subtype classifiers and evaluate differences in prognosis and treatment response based on cfDNA-based subtyping. Citation Format: Rensheng Wan, Raunak Shrestha, Gulfem Guler, Yuhong Ning, Aishwarya Subramanian, Adam Foye, Meng Zhang, Xiaolin Zhu, Thaidy Moreno-Rodriguez, Haolong Li, Shuang G. Zhao, SU2C/PCF West Coast Prostate Cancer Dream Team, Joshi J. Alumkal, Rahul Aggarwal, Alexander W. Wyatt, David Quigley, Samuel Levy, Eric Small, Felix Feng, Martin Sjöström. 5hmC-sequencing of matched cfDNA and tissue from men with mCRPC is concordant and identifies loss of AR signaling in NEPC and DNPC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1985.

Prostate cancer is the second most common cancer among men. Despite advances in diagnosis and management, prostate cancer led to more than 300,000 deaths globally in 2020. Chemotherapy is a cornerstone of therapy for advanced prostate cancer and can prolong survival of patients with both castration-sensitive and castration-resistant disease. Herein, we present a comprehensive review of the data supporting implementation of chemotherapy in the modern treatment of advanced prostate cancer, with special attention to the use of chemotherapy for aggressive variant prostate cancer (e.g., neuroendocrine prostate cancer) and the combination of chemotherapy with androgen signaling inhibitors. As the field of prostate cancer research continues to rapidly evolve yielding novel agents and treatment modalities, chemotherapy continues to play an essential role in prolonging the survival of patients with advanced and metastatic prostate cancer.