Prostate Cancer Outcomes Research Articles

114 Stereotactic Body Radiation Therapy (SBRT) and Hypo-Fractionated Radiation Therapy (HFRT) Outcomes for Low and Intermediate-Risk Prostate Cancer (PRCA): Experience at Two Ontario Centres

114 Stereotactic Body Radiation Therapy (SBRT) and Hypo-Fractionated Radiation Therapy (HFRT) Outcomes for Low and Intermediate-Risk Prostate Cancer (PRCA): Experience at Two Ontario Centres

172 The Impact of Androgen-Deprivation Therapy on Ceramides, a Potential Biomarker of Outcomes of Prostate Cancer for Patients Treated with EBRT and HDR Brachytherapy Boost

172 The Impact of Androgen-Deprivation Therapy on Ceramides, a Potential Biomarker of Outcomes of Prostate Cancer for Patients Treated with EBRT and HDR Brachytherapy Boost

Oral 35 - Sociodemographic Disparities in Prostate Cancer Presentation based on results from the Irish Prostate Cancer Outcomes Research (IPCOR) Study

Oral 35 - Sociodemographic Disparities in Prostate Cancer Presentation based on results from the Irish Prostate Cancer Outcomes Research (IPCOR) Study

Impact of androgen receptor alterations on cell-free DNA genomic profiling on survival outcomes in metastatic castration-resistant prostate cancer.

Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.

Comparing Patient-reported Functional Outcomes After Radical Prostatectomy in Historical and Contemporary Practice.

Modifications to surgical technique, particularly the widespread adoption of robotic surgery, have been proposed to improve functional recovery after prostate cancer surgery. However, rigorous comparison of men in historical vs contemporary practice to evaluate the cumulative effect of these changes on urinary and sexual function after radical prostatectomy is lacking. We compared prospectively collected patient-reported urinary and sexual function from historical (PROSTQA [Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment study], n=235) and contemporary (MUSIC-PRO [Michigan Urological Surgery Improvement Collaborative Patient Reported Outcome] registry, n=1,215) cohorts at the University of Michigan to understand whether modern techniques have resulted in functional improvements for men undergoing prostate cancer surgery. We found significant differences in baseline function, with better urinary (median [IQR]; 100 [93.8-100] vs 93.8 [85.5-100], P < .001) and sexual scores (median [IQR]; 83.3 [66.7-100] vs 74.4 [44.2-87.5], P < .001) prior to treatment in PROSTQA compared to MUSIC-PRO patients, respectively. There was no statistically significant difference in the pattern of urinary incontinence recovery after surgery from 6-24 months between groups (P = .14). However, men in the contemporary MUSIC-PRO group did have significantly better recovery of sexual function compared to men in the historical PROSTQA group (P < .0001). Further, we found that contemporary practice consists of men with more unfavorable demographic and clinical characteristics compared to historical practice. Our results demonstrate that the widespread alterations in prostate cancer surgery over the past 2 decades have yielded improvements in sexual, but not urinary, function recovery.

Developing a Core Outcome Set for Assessing Clinical Safety Outcomes of Prostate Cancer in Clinical Trials of Traditional Chinese Medicine: Protocol for a Mixed Methods Study.

Among the common malignant tumors in men worldwide, the incidence of prostate cancer ranks second to lung cancer. This disease will bring an economic burden to patients and their families and can reduce the quality of life of patients. Researchers have conducted numerous clinical trials on the efficacy and safety of different interventions in the treatment of prostate cancer with traditional Chinese medicine (TCM) combined with standard treatment regimens. However, the currently published clinical trials exhibit inconsistent and irregular reporting of outcome measures. The objective of this paper is to emphasize the need for a core outcome set (COS) to facilitate future prostate cancer research, aiming to improve the quality of trials and generate high-quality evidence. This mixed methods project has three phases, as follows: (1) a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of interventions involving TCM for the treatment of prostate cancer as well as a qualitative component using interviews to obtain the views of patients with prostate cancer, their families, and their caregivers who have a history of TCM treatment; (2) a Delphi survey among stakeholders to prioritize the core outcomes-Participants will include traditional Chinese and Western medicine clinicians in prostate cancer-related directions, nurses, and methodology experts who will participate in 2 rounds of the Delphi method expert consultation to score each outcome in the list of outcome indicators; and (3) a face-to-face consensus meeting to discuss and agree on the final COS for the application of TCM in the treatment of prostate cancer. The protocol has been registered in PROSPERO (CRD42022356184) before the start of the review process, and we will initiate the review on August 1, 2023; results should be expected by September 1, 2023. The Delphi survey among stakeholders is expected to start in October 2023. The development of a core outcome set for assessing clinical safety outcomes of prostate cancer in clinical trials of TCM will provide a significant first step to assist Chinese doctors, researchers, and policy makers. PROSPERO CRD42022356184; https://tinyurl.com/ysakz74r. PRR1-10.2196/46794.

Mid-term oncologic outcomes of radical prostatectomy in lymph node metastatic prostate cancer patients.

Lymph node invasion (LNI) has been reported in 10-15% of pelvic lymph node dissection during radical prostatectomy (RP). The objective of this study was to describe the mid-term oncological outcomes in prostate cancer (PCa) patients with metastatic lymph node. We conducted a retrospective study at two French referral centers including consecutive cN0 PCa patients who underwent RP and extended pelvic lymph node dissection and had lymph node metastases on final pathological analysis (pN1) between January 2000 and May 2020. Follow-up was per institution, which generally included a PSA level measurement every 3 to 12 months for 5 years and annually thereafter. A total of 123 patients were included: two (1.6%) low-risk, 64 (52%) intermediate-risk and 57 (46.4%) high-risk PCa according to the D'Amico risk classification. The median number of nodes removed and metastatic nodes per patient was 15 (IQR 11-22) and 1 (IQR 1-2), respectively. Adverse pathological features, i.e., ≥pT3a stage, ISUP grade ≥3, and positive surgical margins were reported in 113 (91.9%), 103 (83.7%), and 73 (59%) of cases, respectively. Postoperative treatment was administered in 104 patients, including radiotherapy alone (n=6), androgen deprivation therapy alone (n=27) or combination with androgen deprivation therapy and radiotherapy (n=71). The mean follow-up was 42.7 months. The estimated 3-year biochemical-free survival, clinical recurrence-free survival, and cancer-specific survival was 66% and 85% and 98.8%, respectively. In Cox regression analysis, the number of metastatic nodes was associated with clinical recurrence (P=0.04) and a persistently elevated PSA with biochemical recurrence (P<0.001). The management of lymph node metastatic PCa patients is challenging. Risk stratification of node-positive patients, based on postoperative PSA levels and pathologic features being identified, should help physicians determine which patient would best benefit from multimodal treatment.

Integrative analysis of the SOX family-related prognostic signature and immunological infiltration in prostate cancer.

Prostate cancer (PCa) remains a major prevalent cancer worldwide and has a poor prognosis. The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family is a series of transcription factors (TFs) involved in regulating many biological processes (BPs). In tumors, however, SOX genes are frequently deregulated. Tumorigenic deregulation took place at the transcriptional, translational, and posttranslational levels. This leads them to be correlated to tumor progression and poor clinical outcomes in PCa. Nevertheless, the SOX family prognostic role in PCa still needs further investigation. A SOX family-related prognostic signature was developed by performing LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. The construction of a lncRNA-miRNA-mRNA regulatory axis for PCa was performed using a ceRNA network. Upregulation was observed in the expression of SOX4/8/11/12/14, while downregulation was observed for SOX2/5/7/13/15/30 in PCa. Consensus clustering identified four clusters of PCa patients based on these differentially expressed SOX family members. The constructed SOX family-related prognostic signature, which includes five SOX family members (SOX5/8/11/12/30), performed well in predicting PCa-patient prognosis. B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cell immune infiltration levels had a significant association with PCa-patient risk scores. Based on additional analysis, a significant association was also suggested between SOX family expression and tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity. By constructing a ceRNA network, a lncRNA SGMS1-AS1/miR-194-5p/SOX5 regulatory axis was developed for PCa. Herein, a SOX family-related prognostic signature was identified and was found to perform well in predicting PCa-patient prognosis. A lncRNA SGMS1-AS1/miR-194-5p/SOX5 regulatory axis was also identified for PCa progression.

Prostate cancer outcomes following whole-gland and focal high-intensity focused ultrasound.

To report the 5-year failure-free survival (FFS) following high-intensity focused ultrasound (HIFU). This observational cohort study used linked National Cancer Registry data, radiotherapy data, administrative hospital data and mortality records of 1381 men treated with HIFU for clinically localised prostate cancer in England. The primary outcome, FFS, was defined as freedom from local salvage treatment and cancer-specific mortality. Secondary outcomes were freedom from repeat HIFU, prostate cancer-specific survival (CSS) and overall survival (OS). Cox regression was used to determine whether baseline characteristics, including age, treatment year, T stage and International Society of Urological Pathology (ISUP) Grade Group were associated with FFS. The median (interquartile range [IQR]) follow-up was 37 (20-62) months. The median (IQR) age was 65 (59-70) years and 81% had an ISUP Grade Group of 1-2. The FFS was 96.5% (95% confidence interval [CI] 95.4%-97.4%) at 1 year, 86.0% (95% CI 83.7%-87.9%) at 3 years and 77.5% (95% CI 74.4%-80.3%) at 5 years. The 5-year FFS for ISUP Grade Groups 1-5 was 82.9%, 76.6%, 72.2%, 52.3% and 30.8%, respectively (P < 0.001). Freedom from repeat HIFU was 79.1% (95% CI 75.7%-82.1%), CSS was 98.8% (95% CI 97.7%-99.4%) and OS was 95.9% (95% CI 94.2%-97.1%) at 5 years. Four in five men were free from local salvage treatment at 5 years but treatment failure varied significantly according to ISUP Grade Group. Patients should be appropriately informed with respect to salvage radical treatment following HIFU.

Bone marrow sparing in prostate cancer patients treated with Post-operative pelvic nodal radiotherapy – A proton versus photon comparison

PurposeExtending salvage radiotherapy to treat the pelvic lymph nodes (PLNRT) improves oncologic outcomes in prostate cancer (PCa). However, a larger treatment volume increases the extent of bone marrow (BM) exposure, which is associated with hematologic toxicity (HT). Given the potential long-term impact of BM dose in PCa, clinical studies on BM sparing (BMS) are warranted. Herein, we dosimetrically compared photon and proton plans for BMS. Materials and MethodsTreatment plans of 20 post-operative PCa patients treated with volumetric-modulated arc photon therapy (VMAT) PLNRT were retrospectively identified. Contours were added for the whole pelvis BM (WPBM) and BM sub-volumes: lumbar-sacral (LSBM), iliac (ILBM), and lower pelvis (LPBM). Three additional plans were created: VMAT_BMS, intensity-modulated proton therapy (IMPT), and IMPT_BMS. Normal tissue complication probabilities (NTCP) for grade >3 hematologic toxicity (HT3+) were calculated for the WPBM volumes. ResultsCompared to the original VMAT plan, mean doses to all BM sub-volumes were statistically significantly lower for VMAT_BMS, IMPT, and IMPT_BMS resulting in average NTCP percentages of 20.5 ± 5.9, 10.7 ± 4.2, 6.1 ± 2.0, and 2.5 ± 0.6, respectively. IMPT_BMS had significantly lower low dose metrics (V300cGy-V2000cGy) for WPBM and sub-volumes except for LPBM V2000cGy compared to VMAT_BMS and ILBM V20Gy compared to IMPT. In most cases, V4000cGy and V5000cGy within ILBM and LSBM were significantly higher for IMPT plans compared to VMAT plans. ConclusionsBMS plans are achievable with VMAT and IMPT without compromising target coverage or OARs constraints. IMPT plans were overall better at reducing mean and NTCP for HT3+ as well as low dose volumes to BM. However, IMPT had larger high dose volumes within LSBM and ILBM. Further studies are warranted to evaluate the clinical implications of these findings.

Association between greenspace and cancer: evidence from a systematic review and meta-analysis of multiple large cohort studies.

Cancer is a chronic disease that seriously endangers human health, and studies on its association with greenspace have been published. We aimed to systematically review the epidemiological evidence and obtain the best available evidence. PubMed, Web of Science, Embase, and Cochrane Library were used as search databases, the time limit was September 12, 2022, and the cited articles were manually supplemented. Two researchers independently performed literature screening and data extraction. We performed a meta-analysis of data using a normalized difference vegetation index (NDVI) as the greenspace measure, providing hazard ratio (HR) and corresponding 95% CI. After standardization of the data, we used a random effects model for pooling. We also assessed the risk of bias for each study and the quality of each evidence body. We identified 10,108 items and included 14 studies from 11 institutions in eight countries. All studies had a low risk of bias. Quantitative analysis of 13 studies found a beneficial association of greenspace with the mortality of lung cancer (pooled HR [95% CI]=0.965 [0.947, 0.983]) and prostate cancer (HR [95% CI]=0.939 [0.898, 0.980]) based on 0.1-unit NDVI increment and a potential beneficial association with the incidence of prostate, lung, and breast cancer. Greenspace had opposite associations with cancer mortality for urban and rural populations. Indirect comparisons did not find statistically significant differences in the effects of greenspace on different cancer outcomes. The evidence body assessment was considered to be "very low." This review indicated potential beneficial associations between greenspace for lung, prostate, and breast cancer outcomes. However, there was a lack of mediation analysis to explore the underlying mechanism of a causal association. Meanwhile, the interstudy heterogeneity was large. Therefore, future studies should consider more accurate exposure assessment and more comprehensive covariate coverage, while focusing on mediating analysis. PROSPERO: CRD42022361068.

Real-world evidence of outcomes of oligometastatic hormone-sensitive prostate cancer patients treated with metastasis-directed therapy.

To investigate characteristics and outcomes of oligometastatic hormone-sensitive prostate cancer (mHSPC) patients undergoing metastases-directed therapy (MDT) with external beam radiation therapy (EBRT). We relied on an institutional tertiary-care database to identify mHSPC patients who underwent EBRT as MDT between 12/2019 and 12/2022. Main outcomes consisted of progression to metastatic castration-resistant prostate cancer (mCRPC) and overall mortality (OM). Oligometastatic was defined as ≤3 metastases and bone and/or lymph node deposits were treated with conventional doses up to 54 Gy or with hypofractionated stereotactic regimes of median 24 Gy (20-27 Gy). Overall, 37 patients treated with EBRT as MDT were identified. The median follow-up was 13 months. Median age at MDT was 71 years and 84% exhibited ECOG performance status 0. The median baseline PSA at diagnosis was 10 ng/mL. Overall, primary local therapy consisted of radical prostatectomy (65%), followed by external beam radiation therapy to the prostate (11%), focal therapy (8%), and palliative transurethral resection of the prostate (5%). Overall, 32% exhibited de novo oligometastatic mHSPC. Bone metastases were present in 78% versus 19% lymph node metastases versus 3% both. The distribution of targeted oligo-metastases was 62% versus 38% for respectively one metastasis versus more than one metastasis. Androgen deprivation therapy (ADT) was combined with MDT in 84%. Moreover, 19% received combination therapy with apalutamide/enzalutamide and 12% with abiraterone or docetaxel. The median time to mCRPC was 50 months. In incidence analyses, 13% developed mCRPC after 24 months. OM after 24 months was 15% in mHSPC patients receiving MDT. Significant OM differences were observed after stratification into targeted metastatic burden (<0.05). No high-grade adverse events were recorded during MDT. Our real-world data suggest that MDT represents a safe treatment option for well-selected oligometastatic mHSPC patients.

Association of quantifiable prostate MRI parameters with any and large cribriform pattern in prostate cancer patients undergoing radical prostatectomy

PurposeCribriform pattern has recently been recognized as an important independent risk factor for prostate cancer (PCa) outcome. This study aimed to identify the association of quantifiable prostate magnetic resonance imaging (MRI) parameters with any and large cribriform pattern at radical prostatectomy (RP) specimens. MethodsPreoperative prostate MRI’s from 188 men undergoing RP between 2010 and 2018 were retrospectively acquired. RP specimens of the patients were revised for Gleason score (GS), and presence of any and large cribriform pattern. MRI parameters such as MRI visibility, PI-RADS score, lowest apparent diffusion coefficient (ADC) value, lesion size, and radiologic extra-prostatic extension (EPE) were reviewed. The association of prostate MRI parameters for presence of any and large cribriform pattern at RP was analysed using logistic regression. Results116/188 (61.7%) PCa patients had any cribriform and 36/188 (19.1%) large cribriform pattern at RP. 171/188 (91.0%) men had MRI-visible lesions; 111/116 (95.7%) tumours with any and 36/36 (100%) with large cribriform pattern were visible at MRI. PCa with any and large cribriform pattern both had lower ADC values than those without (p < 0.001). In adjusted analysis, lowest ADC value was as an independent predictor for any cribriform (Odds Ratio (OR) 0.2, 95% Confidence Interval (CI) 0.1–0.8; p = 0.01) and large cribriform pattern (OR 0.2, 95% CI 0.1–0.7; p = 0.01), while other parameters were not. ConclusionsThe majority of PCa with cribriform pattern at RP were visible at MRI, and lowest ADC value was an independent predictor for both any and large cribriform pattern.

Are associations between obesity and prostate cancer outcomes following radical prostatectomy the same in smokers and non-smokers? Results from the SEARCH Cohort.

Obesity and smoking have been associated with poor prostate cancer (PC) outcomes. We investigated associations between obesity and biochemical recurrence (BCR), metastasis, castrate resistant-PC (CRPC), PC-specific mortality (PCSM), and all-cause mortality (ACM) and examined if smoking modified these associations. We analyzed SEARCH Cohort data from men undergoing RP between 1990 and 2020. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between body mass index (BMI) as a continuous variable and weight status classifications (normal: 18.5 ≤ 25kg/m2; overweight: 25-29.9kg/m2; obese: ≥ 30kg/m2) and PC outcomes. Among 6,241 men, 1,326 (21%) were normal weight, 2,756 (44%) overweight and 2159 (35%) obese; 1,841 (30%) were never-smokers, 2,768 (44%) former and 1,632 (26%) current-smokers. Among all men, obesity was associated with non-significant increased risk of PCSM, adj-HR = 1.71; 0.98-2.98, P = 0.057, while overweight and obesity were inversely associated with ACM, adj-HR = 0.75; 0.66-0.84, P < 0.001 and adj-HR = 0.86; 0.75-0.99, P = 0.033, respectively. Other associations were null. BCR and ACM were stratified for smoking status given evidence for interactions (P = 0.048 and P = 0.054, respectively). Among current-smokers, overweight was associated with an increase in BCR (adj-HR = 1.30; 1.07-1.60, P = 0.011) and a decrease in ACM (adj-HR = 0.70; 0.58-0.84, P < 0.001). Among never-smokers, BMI (continuous) was associated with an increase in ACM (adj-HR = 1.03; 1.00-1.06, P = 0.033). While our results are consistent with obesity as a risk factor for PCSM, we present evidence of effect modification by smoking for BCR and ACM highlighting the importance of stratifying by smoking status to better understand associations with body weight.

Improving Treatment Intensification for Better Outcomes in Prostate Cancer

Improving Treatment Intensification for Better Outcomes in Prostate Cancer

Androgen-regulated stromal complement component 7 (C7) suppresses prostate cancer growth.

The complement system is a major component of the innate immune system that works through the cytolytic effect of the membrane attack complex (MAC). Complement component 7 (C7) is essential for MAC assembly and its precisely regulated expression level is crucial for the cytolytic activity of MAC. We show that C7 is specifically expressed by the stromal cells in both mouse and human prostates. The expression level of C7 inversely correlates with clinical outcomes in prostate cancer. C7 is positively regulated by androgen signaling in the mouse prostate stromal cells. The androgen receptor directly transcriptionally regulates the mouse and human C7. Increasing C7 expression in the C57Bl/6 syngeneic RM-1 and Pten-Kras allografts suppresses tumor growth in vivo. Conversely, C7 haploinsufficiency promotes tumor growth in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Interestingly, replenishing C7 in androgen-sensitive Pten-Kras tumors during androgen depletion only slightly enhances cellular apoptosis, highlighting the diverse mechanisms employed by tumors to counteract complement activity. Collectively, our research indicates that augmenting complement activity could be a promising therapeutic approach to impede the development of castration resistance in prostate cancer.

High SLC20A1 Expression Indicates Poor Prognosis in Prostate Cancer.

High expression of solute carrier family 20 member 1 (SLC20A1) indicates poor clinical outcomes for patients with breast cancer subtypes treated with endocrine therapy and radiotherapy. However, the association between SLC20A1 expression and clinical outcomes in prostate cancer remains to be determined. Open-source datasets (The Cancer Genome Atlas prostate, Stand Up to Cancer-Prostate Cancer Foundation Dream Team, and The Cancer Genome Atlas PanCancer Atlas) were downloaded and analyzed. SLC20A1 expression was analyzed in prostate cancer and normal prostate tissue. Survival analysis using Kaplan-Meier curves and Cox regression analysis were performed to examine patient prognosis, as well as the effects of endocrine therapy and radiotherapy on high SLC20A1 expression in patients with prostate cancer. SLC20A1 was higher in prostate cancer than in normal prostate tissues. High SLC20A1 expression predicted poor disease-free and progression-free survival. Following endocrine therapy, no significant difference in prognosis was observed between patients with high SLC20A1 and those with low SLC20A1 expression. However, following radiotherapy, high SLC20A1 expression tended to be associated with a poor clinical outcome. SLC20A1 may serve as a prognostic biomarker for prostate cancer, and the recommended treatment for patients with high SLC20A1 expression is endocrine therapy.

Multi-Omic Integration of Blood-Based Tumor-Associated Genomic and Lipidomic Profiles Using Machine Learning Models in Metastatic Prostate Cancer.

To determine prognostic and predictive clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) on the basis of a combination of plasma-derived genomic alterations and lipid features in a longitudinal cohort of patients with advanced prostate cancer. A multifeature classifier was constructed to predict clinical outcomes using plasma-based genomic alterations detected in 120 genes and 772 lipidomic species as informative features in a cohort of 71 patients with mHSPC and 144 patients with mCRPC. Outcomes of interest were collected over 11 years of follow-up. These included in mHSPC state early failure of androgen-deprivation therapy (ADT) and exceptional responders to ADT; early death (poor prognosis) and long-term survivors in mCRPC state. The approach was to build binary classification models that identified discriminative candidates with optimal weights to predict outcomes. To achieve this, we built multi-omic feature-based classifiers using traditional machine learning (ML) methods, including logistic regression with sparse regularization, multi-kernel Gaussian process regression, and support vector machines. The levels of specific ceramides (d18:1/14:0 and d18:1/17:0), and the presence of CHEK2 mutations, AR amplification, and RB1 deletion were identified as the most crucial factors associated with clinical outcomes. Using ML models, the optimal multi-omics feature combination determined resulted in AUC scores of 0.751 for predicting mHSPC survival and 0.638 for predicting ADT failure; and in mCRPC state, 0.687 for prognostication and 0.727 for exceptional survival. The models were observed to be superior than using a limited candidate number of features for developing multi-omic prognostic and predictive signatures. Using a ML approach that incorporates multiple omic features improves the prediction accuracy for metastatic prostate cancer outcomes significantly. Validation of these models will be needed in independent data sets in future.

Trends and variation in prostate cancer diagnosis via transperineal biopsy in Australia and New Zealand.

To describe changes in the use of prostate biopsy techniques among men diagnosed with prostate cancer in Australia and New Zealand and examine factors associated with these changes. We extracted data between 2015 and 2019 from 7 jurisdictions of the Australia and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Distribution and time trend of transrectal (TR) vs. transperineal (TP) biopsy type, differences in the proportion of biopsy type by geographic jurisdiction, diagnosing institute characteristics (public vs. private, metropolitan vs. regional, case volume) and patient characteristics such as socio-economic status (SES), and location of residence were analyzed. We analyzed data from 37,638 patients. The overall proportion of prostate cancer diagnosed by TP increased from 26% to 57% between 2015 and 2019. Patients living in a major city, a more socioeconomically advantaged area or who were diagnosed in a metropolitan or private hospital were more likely to have TP than TR. While all subgroups were observed to increase their use of TP over the study period, uptake grew faster for men from low SES areas and those diagnosed at a regional or low-volume hospital but slower for men living in outer regional/remote areas or treated at a public hospital. In this binational registry, prostate cancer is now more commonly diagnosed by TP than the TR approach. While the gap between uptakes of TP has diminished for patients with low vs. high SES, disparity has widened for patients from outer regional areas vs major cities and public vs. private hospitals.

Prognostic value of a baseline prognostic nutritional index for patients with prostate cancer: a systematic review and meta-analysis.

The prognostic nutritional index (PNI) integrates both nutritional and immune indicators and provides promising prognostic value for various malignancies. However, there is still no specific consensus relating to the precise relationship between the pretreatment PNI and the survival outcome of patients with prostate cancer (PCa). Here, we performed a meta-analysis to determine the prognostic significance of PNI for patients with PCa. We used the PubMed, EMBASE, Web of Science, Cochrane Library (CENTRAL), and CNKI databases to identify and retrieve eligible articles that were published in any language up to the 1st March 2023. Our analysis considered hazard ratios (HRs) and 95% confidence intervals (CIs) published in the included studies. Data synthesis and analysis were conducted using Stata 15.1 software. A total of ten studies featuring 1631 cases were included in our quantitative analysis. Analysis showed that a low PNI at baseline was significantly associated with poor overall survival (OS) (HR: 2.16; 95% CI: 1.40-3.34; p = 0.01), progression-free survival (PFS) (HR: 2.17; 95% CI 1.63-2.89; p < 0.001). Owing to high levels of heterogeneity, we performed subgroup analysis based on disease staging, sample size, and cutoff value; we found that disease staging may have been the source of the heterogeneity. A low pretreatment PNI was associated with poor survival outcomes for both metastatic castration-resistant prostate cancer (mCRPC) patients and nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. A low pretreatment PNI was significantly correlated with a worse OS and PFS in patients with PCa. A low pretreatment PNI may act as a reliable and effective predictor for the prognosis of patients with PCa. Further well-designed studies should be performed to fully evaluate the prognostic performance of this novel indicator for PCa.