Management Of Prostate Cancer Patients Research Articles

The Role of Transurethral BPH Surgeries in Management of Urinary Symptoms in Prostate Cancer Patients, Narrative Review.

Prostate cancer and benign prostate hyperplasia (BPH) are two ubiquitous pathologies that may coexist. A significant percentage of patients with different stages of prostate cancer suffer lower urinary tract symptoms (LUTS) due to associated BPH. We aimed to review the literature regarding the role of transurethral surgeries in the management of prostate cancer patients and the different available management options. The evidence in literature for the use of BPH surgeries in prostate cancer patients is based mainly on low-quality retrospective studies. In patients on active surveillance, BPH surgeries are beneficial in relieving LUTS without oncological risk and can eliminate the contribution of adenoma to PSA level. In patients with advanced prostate cancer, palliative BPH surgery can relieve LUTS and urinary retention with unclear oncological impact; however some reports depict that the need for BPH surgery in advanced prostate cancer is associated with poorer prognosis. In patients receiving radiotherapy, various studies showed that transurethral resection of prostate (TURP) is associated with increased radiotoxicity despite some recent reports encouraging the use of Holmium Laser Enucleation of the Prostate (HoLEP) to improve urinary symptom scores before radiotherapy. The most commonly reported techniques utilized are TURP, photoselective vaporization of prostate (PVP) and HoLEP. The use of BPH surgery is justified for relieving LUTS in selected prostate cancer patients on active surveillance or in advanced stages, however the use in the pre-radiotherapy settings remains controversial. Future prospective and randomized controlled trials are required for validating the benefits and assessing potential hazards.

3058: PSMA-guided management of prostate cancer patients relapsing after prostatectomy and prostate-bed RT

3058: PSMA-guided management of prostate cancer patients relapsing after prostatectomy and prostate-bed RT

Development of preoperative nomograms to predict the risk of overall and multifocal positive surgical margin after radical prostatectomy

ObjectiveTo develop preoperative nomograms using risk factors based on clinicopathological and MRI for predicting the risk of positive surgical margin (PSM) after radical prostatectomy (RP).Patients and methodsThis study retrospectively enrolled patients who underwent prostate MRI before RP at our center between January 2015 and November 2022. Preoperative clinicopathological factors and MRI-based features were recorded for analysis. The presence of PSM (overall PSM [oPSM]) at pathology and the multifocality of PSM (mPSM) were evaluated. LASSO regression was employed for variable selection. For the final model construction, logistic regression was applied combined with the bootstrap method for internal verification. The risk probability of individual patients was visualized using a nomogram.ResultsIn all, 259 patients were included in this study, and 76 (29.3%) patients had PSM, including 40 patients with mPSM. Final multivariate logistic regression revealed that the independent risk factors for oPSM were tumor diameter, frank extraprostatic extension, and annual surgery volume (all p < 0.05), and the nomogram for oPSM reached an area under the curve (AUC) of 0.717 in development and 0.716 in internal verification. The independent risk factors for mPSM included the percentage of positive cores, tumor diameter, apex depth, and annual surgery volume (all p < 0.05), and the AUC of the nomogram for mPSM was 0.790 in both development and internal verification. The calibration curve analysis showed that these nomograms were well-calibrated for both oPSM and mPSM.ConclusionsThe proposed nomograms showed good performance and were feasible in predicting oPSM and mPSM, which might facilitate more individualized management of prostate cancer patients who are candidates for surgery.

Role of Lutetium Radioligand Therapy in Prostate Cancer.

Theranostics utilize ligands that chelate radionuclides and selectively bind with cancer-specific membrane antigens. In the case of prostate cancer (PCa), the state-of-the-art lutetium-177-PSMA combines the radioactive β-emitter 177Lu with Vipivotide Tetraxetan, a prostate-specific membrane antigen (PSMA)-binding ligand. Several studies have been conducted, and the therapy is not without adverse effects (e.g., xerostomia, nausea, and fatigue); however, few events are reported as severe. The available evidence supports the use of 177Lu-PSMA in selected metastatic castration-resistant prostate cancer patients, and the treatment is considered a standard of care in several clinical scenarios. Emerging research shows promising results in the setting of hormone-sensitive prostate cancer; however, evidence from high-quality controlled trials is still missing. In this review, we discuss the available evidence for the application of 177Lu-PSMA in the management of PCa patients.

Rational design of NT-PSMA heterobivalent probes for prostate cancer theranostics.

Targeting the prostate-specific membrane antigen (PSMA) with radiopharmaceuticals for imaging and/or therapy has demonstrated significant advancement in the management of prostate cancer patients. However, PSMA targeting remains unsuccessful in prostate cancers with low expression of PSMA, which account for 15% of cases. The neurotensin receptor-1 (NTS1) has been highlighted as a suitable oncotarget for imaging and therapy of PSMA-negative prostate cancer lesions. Therefore, heterobivalent probes targeting both PSMA and NTS1 could improve the prostate cancer management. Herein, we report the development of a branched hybrid probe (JMV 7489) designed to target PSMA and/or NTS1 bearing relevant pharmacophores and DOTA as the chelating agent. The new ligand was synthesized with a hybrid approach, which includes both syntheses in batch and in the solid phase. Saturation binding experiments were next performed on HT-29 and PC3-PIP cells to derive K d and B max values. On the PC3-PIP cells, [68Ga]Ga-JMV 7489 displayed good affinity towards PSMA (K d = 53 ± 17 nM; B max = 1393 ± 29 fmol/106 cells) in the same range as the corresponding reference monomer. A lower affinity value towards NTS1 was depicted (K d = 157 ± 71 nM; B max = 241 ± 42 fmol/106 cells on PC3-PIP cells; K d = 246 ± 1 nM; B max = 151 ± 44 fmol/106 cells on HT-29 cells) and, surprisingly, it was also the case for the corresponding monomer [68Ga]Ga-JMV 7089. These results indicate that the DOTA macrocycle and the linker are critical elements to design heterobivalent probes targeting PSMA and NTS1 with high affinity towards NTS1.

Personalized dietary management of advanced prostate cancer using nutrigenomics: a case report

While there are emerging reports in the scientific literature on potential associations between cholesterol/lipids and prostate cancer, information on the dietary management of these cancer patients is currently lacking. We report on a 57-year-old white Australian male diagnosed with advanced prostate cancer who had personalized dietary management in preparation for and following his medical treatment: radiation and radical prostatectomy. Dietary recommendations were based on his blood results and nutrigenomic tests which showed a history of and genetic predisposition to dyslipidemia. Nutritional analysis also confirmed the need for dietary modification of his fat intake. Eighteen months post medical and dietary intervention his PSA level was reported at 0.1 ug/L and all blood lipid levels were within reference ranges. At two years there was no detectable disease recurrence and androgen deprivation therapy (ADT) was not required. Personalized dietary recommendations could be a clinically beneficial addition to the multidisciplinary management of prostate cancer patients.

Radiomics for the identification of extraprostatic extension with prostate MRI: a systematic review and meta-analysis

ObjectivesExtraprostatic extension (EPE) of prostate cancer (PCa) is predicted using clinical nomograms. Incorporating MRI could represent a leap forward, although poor sensitivity and standardization represent unsolved issues. MRI radiomics has been proposed for EPE prediction. The aim of the study was to systematically review the literature and perform a meta-analysis of MRI-based radiomics approaches for EPE prediction.Materials and methodsMultiple databases were systematically searched for radiomics studies on EPE detection up to June 2022. Methodological quality was appraised according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and radiomics quality score (RQS). The area under the receiver operating characteristic curves (AUC) was pooled to estimate predictive accuracy. A random-effects model estimated overall effect size. Statistical heterogeneity was assessed with I2 value. Publication bias was evaluated with a funnel plot. Subgroup analyses were performed to explore heterogeneity.ResultsThirteen studies were included, showing limitations in study design and methodological quality (median RQS 10/36), with high statistical heterogeneity. Pooled AUC for EPE identification was 0.80. In subgroup analysis, test-set and cross-validation-based studies had pooled AUC of 0.85 and 0.89 respectively. Pooled AUC was 0.72 for deep learning (DL)–based and 0.82 for handcrafted radiomics studies and 0.79 and 0.83 for studies with multiple and single scanner data, respectively. Finally, models with the best predictive performance obtained using radiomics features showed pooled AUC of 0.82, while those including clinical data of 0.76.ConclusionMRI radiomics–powered models to identify EPE in PCa showed a promising predictive performance overall. However, methodologically robust, clinically driven research evaluating their diagnostic and therapeutic impact is still needed.Clinical relevance statementRadiomics might improve the management of prostate cancer patients increasing the value of MRI in the assessment of extraprostatic extension. However, it is imperative that forthcoming research prioritizes confirmation studies and a stronger clinical orientation to solidify these advancements.Key Points• MRI radiomics deserves attention as a tool to overcome the limitations of MRI in prostate cancer local staging.• Pooled AUC was 0.80 for the 13 included studies, with high heterogeneity (84.7%, p < .001), methodological issues, and poor clinical orientation.• Methodologically robust radiomics research needs to focus on increasing MRI sensitivity and bringing added value to clinical nomograms at patient level.

Genetic testing and management of prostate cancer patients with pathogenic germline variants

SummaryProstate cancer (PCa) is an androgen-receptor signaling-dependent disease with a subset of patients harboring pathogenic germline variants (PGVs) in genes essential for DNA repair. In the last decade, several guidelines and recommendations have been developed to define which PCa patients should receive genetic testing to identify individuals at higher risk due to inherited alterations and to facilitate personalized treatment strategies. Notably, the presence of specific germline alterations in carriers undergoing PCa screening has implications for screening strategies, and PGV carriers with advanced disease are eligible to receive targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi) or immune checkpoint inhibitors (CKI) depending on the alterations encountered. Although less information is available on carriers with localized disease, several trials are addressing this specific patient population and will help to collect data and improve clinical management of PCa patients with PGVs.

P097 - How does PSMA PET/CT influence the management of prostate cancer patients?

P097 - How does PSMA PET/CT influence the management of prostate cancer patients?

Perspectives on prostate cancer: advances and pending challenges for a multidisciplinary oncological approach in South America.

Prostate cancer is one of the tumors with the highest incidence and mortality among men worldwide, and this situation is no different in South America. However, epidemiological data are highly variable for each country and even more so than in North America. These data may be influenced by the very low rate of early detection of disease, availability of diagnostic methods, proper data collection, and limited access to specialized multidisciplinary treatment. For many South American countries, academic referral centers can only offer state-of-the-art diagnostics and multidisciplinary cancer treatment for patients who live in or can travel to large cities, so most patients are cared for by non-expert urologists with limited resources, which can have a negative impact on their prognosis and worsen oncologic outcomes. We aimed to show the clinical management of prostate cancer patients, the current advances in management, limitations present in South America, and how a multidisciplinary approach in referral cancer centers conformed of specialized urologists, medical oncologists, and mental health professionals can maximize patient outcomes.

Omics sciences and precision medicine in prostate cancer.

In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.

Clinical Audit of the Use of Choline/PSMA-PET-CT in Prostate Cancer Patients at Weston Park Cancer Centre, January 2019–December 2021

Purpose: Positron emission tomography (PET)-CT is increasingly utilised in the management of prostate cancer patients. There is variability in the integration of PET-CT into clinical management. This project reviewed available literature to define standards, against which local use of PET-CT was audited.

How the Analysis of the Pathogenetic Variants of DDR Genes Will Change the Management of Prostate Cancer Patients.

Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate cancer (PC) patients. The incidence of PVs in homologous recombination repair (HRR) genes among men with metastatic PC varied between 11% and 33%, which was significantly higher than that in non-metastatic PC, and BRCA2 mutations were more frequent when compared to other DDR genes. The determination of the somatic or germline PVs of BRCA2 was able to define a tailored therapy using PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) progression after first-line therapy, with significant improvements in the radiologic progression-free survival (rPFS) and overall survival (OS) rates. We propose testing all metastatic PC patients for somatic and germline HRR mutations. Somatic determination on the primary site or on historic paraffin preparations with a temporal distance of no longer than 5 years should be preferred over metastatic site biopsies. The prognostic use of DDR PVs will also be used in selected high-risk cases with non-metastatic stages to better arrange controls and therapeutic primary options. We anticipate that the use of poly-ADP-ribose polymerase (PARP) inhibitors in hormone-sensitive prostate cancer (HSPC) and in combination with androgen receptor signaling inhibitors (ARSI) will be new strategies.

Prostatic high-resolution micro-ultrasound: an attractive step-forward in the management of prostate cancer patients.

Prostatic high-resolution micro-ultrasound: an attractive step-forward in the management of prostate cancer patients.

Development and pilot-testing of the expanded prostate index composite - Filipino version (EPIC-F).

Quality-of-life (QOL) is paramount in clinical decision-making in the management of prostate cancer patients. The expanded prostate index composite (EPIC) is a widely used and well-validated QOL tool that allows for the evaluation of bowel, urinary, sexual, and hormonal domains. A Filipino translation was previously lacking. We describe the development and pilot testing of the Filipino translation of the EPIC (EPIC-F). The EPIC-32 was translated into Filipino using iterative forward and backward procedures with checks for semantic congruency. The translation was then evaluated by an expert panel consisting of a prostate cancer survivor and pertinent health professionals. A focused group discussion (FGD) was conducted to explore sources of difficulty of use to guide improvement. The linguistically validated translation was evaluated to have cultural relevancy, adequacy, and representativeness by the expert panel, and to have good understandability and answerability by a representative pilot cohort of prostate cancer patients. Seven unsatisfactory items were identified, all pertaining to the sexual domain, and required minimal revision on review during the FGD. The EPIC-F is a linguistically and culturally validated version of the EPIC 32, with good understandability and answerability, permitting clinical use. Its psychometric properties need to be determined to define its utility in clinical research.

A Novel Angiogenesis-Related Gene Signature to Predict Biochemical Recurrence of Patients with Prostate Cancer following Radical Therapy

Background Prostate cancer (PCa) is one of the most common malignancies in males; we aim to establish a novel angiogenesis-related gene signature for biochemical recurrence (BCR) prediction in PCa patients following radical therapy. Methods Gene expression profiles and corresponding clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We quantified the levels of various cancer hallmarks and identified angiogenesis as the primary risk factor for BCR. Then machine learning methods combined with Cox regression analysis were used to screen prognostic genes and construct an angiogenesis-related gene signature, which was further verified in external cohorts. Furthermore, estimation of immune cell abundance and prediction of drug responses were also conducted to detect potential mechanisms. Results Angiogenesis was regarded as the leading risk factor for BCR in PCa patients (HR = 1.58, 95% CI: 1.38–1.81), and a novel prognostic signature based on three genes (NRP1, JAG2, and VCAN) was developed in the training cohort and successfully validated in another three independent cohorts. In all datasets, this signature was identified as a prognostic factor with promising and robust predictive values. Moreover, it also predicted higher infiltration of regulatory T cells and M2-polarized macrophages and increased drug sensitivity of angiogenesis inhibitors in high-risk patients. Conclusions The angiogenesis-related three-gene signature may serve as an independent prognostic factor for BCR, which would contribute to risk stratification and personalized management of PCa patients after radical therapy in clinical practice.

Abstract LB150: Clinical outcome prediction of prostate cancer using machine learning based on fusion gene detection

Abstract Prediction of the clinical outcomes of prostate cancer remains a challenge. Recently, we discovered a panel of 8 fusion genes that occurred in aggressive prostate cancer. In order to make the fusion gene test clinically ready as a predictor, we have modified to test into a semi-quantitative Taqman QRT-PCR. In the funding period, Two hundred seventy-one prostate cancer samples with clinical follow-up were collected from University of Pittsburgh Medical Center. In addition, 194 prostate cancer samples from University of Wisconsin, Madison and 108 prostate cancer samples from Stanford University were collected. Taqman QRT-PCRs were performed on these samples. Significant numbers of samples were found positive for some of these fusion genes. The expression of MAN2A1-FER, SLC45A2-AMACR, MTOR-TP53BP1 fusions are associated with prostate cancer recurrence in the UPMC cohort. Cross-validation showed that fusion gene model predicts up to 91% clinical outcomes of prostate cancer accurately. When cohorts of UPMC, Stanford and Wisconsin were combined, the accuracy is 74%. The combination of fusion with Gleason appeared to improve the overall accuracy from 77% (Gleason) to 92% (Gleason+fusion) in the UPMC cohort, and from 71% (Gleason) to 82% (Gleason+fusion) when all three cohorts are combined. When fusion combined with both pathology stage and Gleason, the accuracy was improved a little further: 93% accuracy in the UPMC cohort and 83% when all three cohorts are combined. In summary, fusion transcript prediction model may have a role in prostate cancer prognosis prediction and guiding the management of prostate cancer patients. Citation Format: Jian-Hua Luo, Silvia Liu, Yan-Ping Yu. Clinical outcome prediction of prostate cancer using machine learning based on fusion gene detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB150.

Advances in PSMA theranostics

The validation of prostate specific membrane antigen (PSMA) as a molecular target in metastatic castration-resistant prostate cancer has stimulated the development of multiple classes of theranostic ligands that specifically target PSMA. Theranostic ligands are used to image disease or selectively deliver cytotoxic radioactivity to cells expressing PSMA according to the radioisotope conjugated to the ligand. PSMA theranostics is a rapidly advancing field that is now integrating into clinical management of prostate cancer patients. In this review we summarize published research describing the biological role(s) and activity of PSMA, highlight the most clinically advanced PSMA targeting molecules and biomacromolecules, and identify next generation PSMA ligands that aim to further improve treatment efficacy. The goal of this review is to provide a comprehensive assessment of the current state-of-play and a roadmap to achieving further advances in PSMA theranostics.

The role of prostate-specific membrane antigen PET/computed tomography in the management of prostate cancer patients: could we ask for more?

Thanks to the development of novel PSMA-based peptides, molecular imaging, such as PET/CT paired with theranostic-based approaches have recently been proposed for treatment of prostate cancer. Patient selection, however, remains challenging because of the absence of strong prospective data to interpret and translate imaging scans into effective and well tolerated treatment regimens. In this review, we discuss the latest findings in PSMA imaging in prostate cancer patients. Particularly, we go into detail into the impact of PSMA imaging on the treatment management in primary staging, biochemical recurrence and in advanced prostate cancer. For primary prostate cancer staging, PSMA PET/CT seems crucial for primary therapy assessment, being able in some cases to detect lesions outside the surgical template, thus permitting a change in management. Moreover, N+ condition at PSMA has been correlated with a worse biochemical recurrence-free and therapy-free survival. The early detection of PSMA-positive findings in recurrent prostate cancer is associated with a better time to relapse survival. Similarly, for advanced prostate cancer patients, accurate restaging with PSMA imaging is gaining importance for early prediction of response to systemic therapies and to assure the best outcome possible. With regards to theranostics, appropriate selection of patients eligible for 177Lu-PSMA requires PSMA imaging, whereas the role of added FDG-PET for discriminating those with PSMA/FDG discordance needs to be further evaluated.

Fusion gene transcripts to predict prostate cancer clinical outcome

Prediction of the clinical outcomes of prostate cancer remains a challenge. Recently, we discovered a panel of 8 fusion genes that occurred in aggressive prostate cancer. In order to make the fusion gene test clinically ready as a predictor, we have modified to test into a semi‐quantitative Taqman QRT‐PCR. In the funding period, Two hundred seventy‐one prostate cancer samples with clinical follow‐up were collected from University of Pittsburgh Medical Center. In addition, 194 prostate cancer samples from University of Wisconsin, Madison and 108 prostate cancer samples from Stanford University were collected. Taqman QRT‐PCRs were performed on these samples. Significant numbers of samples were found positive for some of these fusion genes. The expression of MAN2A1‐FER, SLC45A2‐AMACR, MTOR‐TP53BP1 fusions are associated with prostate cancer recurrence in the UPMC cohort. Cross‐validation showed that fusion gene model predicts up to 91% clinical outcomes of prostate cancer accurately. When cohorts of UPMC, Stanford and Wisconsin were combined, the accuracy is 74%. The combination of fusion with Gleason appeared to improve the overall accuracy from 77% (Gleason) to 92% (Gleason+fusion) in the UPMC cohort, and from 71% (Gleason) to 82% (Gleason+fusion) when all three cohorts are combined. When fusion combined with both pathology stage and Gleason, the accuracy was improved a little further: 93% accuracy in the UPMC cohort and 83% when all three cohorts are combined. In summary, fusion transcript prediction model may have a role in prostate cancer prognosis prediction and guiding the management of prostate cancer patients.