Prognostic Importance of Lymphovascular Invasion for Specific Subgroup of Patients with Prostate Cancer After Robot-Assisted Radical Prostatectomy (The MSUG94 Group).

OBJECTIVE: This study aimed to investigate whether lymphovascular invasion (LVI) was associated with oncological outcomes in patients with prostate cancer (PCa) undergoing robotic-assisted radical prostatectomy (RARP). METHODS: This retrospective multicenter cohort study was conducted on 3195 patients with PCa who underwent RARP in nine institutions in Japan. The primary endpoints were the associations between biochemical recurrence (BCR) and LVI and between BCR and clinicopathological covariates, while the secondary endpoints were the association between LVI and the site of clinical recurrence and metastasis-free survival (MFS). RESULTS: In total, 2608 patients met the inclusion criteria. At the end of the follow-up period, 311 patients (11.9%) were diagnosed with BCR and none died of PCa. In patients with pathological stage T2 (pT2) + negative resection margins (RM-), and pT3+ positive RM (RM+), LVI significantly worsened BCR-free survival (BRFS). For patients with PCa who had pT3 and RM+, the 2-year BRFS rate in those with LVI was significantly worse than in those without LVI. Patients with LVI had significantly worse MFS than those without LVI with respect to pT3, RM+, and pathological Gleason grade (pGG). In multivariate analysis, LVI was significantly associated with BRFS in patients with pT3 PCa, and with worse MFS in PCa patients with pT3, RM+, and pGG ≥ 4. CONCLUSIONS: LVI was an independent prognostic factor for recurrence and metastasis after RARP, particularly in patients with pT3 and RM+ PCa. Locally advanced PCa with positive LVI and RM+ requires careful follow-up because of the high likelihood of recurrence.

Nomogram Predicting Locally Advanced Prostate Cancer in Patients with Clinically Organ-Confined Disease Who Underwent Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (The MSUG94 Group).

PURPOSE: We created a clinically applicable nomogram to predict locally advanced prostate cancer using preoperative parameters and performed external validation using an external independent validation cohort. PATIENTS AND METHODS: From a retrospective multicenter cohort study of 3622 Japanese patients with prostate cancer who underwent robot-assisted radical prostatectomy at ten institutions, the patients were divided into two groups (MSUG cohort and validation cohort). Locally advanced prostate cancer was defined as pathological T stage ≥ 3a. A multivariable logistic regression model was used to identify factors strongly associated with locally advanced prostate cancer. Bootstrap area under the curve was calculated to assess the internal validity of the prediction model. A nomogram was created as a practical application of the prediction model, and a web application was released to predict the probability of locally advanced prostate cancer. RESULTS: A total of 2530 and 427 patients in the MSUG and validation cohorts, respectively, met the criteria for this study. On multivariable analysis, initial prostate-specific antigen, prostate volume, number of cancer-positive and cancer-negative biopsy cores, biopsy grade group, and clinical T stage were independent predictors of locally advanced prostate cancer. The nomogram predicting locally advanced prostate cancer was demonstrated (area under the curve 0.72). Using a nomogram cutoff of 0.26, 464 of 1162 patients (39.9%) could be correctly diagnosed with pT3, and 2311 of 2524 patients (91.6%) could avoid underdiagnosis. CONCLUSIONS: We developed a clinically applicable nomogram with external validation to predict the probability of locally advanced prostate cancer in patients undergoing robot-assisted radical prostatectomy.

The prognostic significance of the clinical T stage and Grade Group in patients with locally advanced prostate cancer treated via high-dose-rate brachytherapy and external beam radiation.

BACKGROUND: Although the optimal management of locally advanced prostate cancer (PCa) remains unclear, local definitive therapy, thus combined radiotherapy and androgen deprivation, is one option. We evaluated the long-term outcomes of patients with locally advanced PCa who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT). METHODS: We retrospectively analyzed 173 patients with locally advanced PCa (cT3a-4N0-1M0) who underwent HDR-BT and EBRT. We employed Cox's proportional hazards models to identify pre-treatment predictors of oncological outcomes. Treatment outcomes (biochemical recurrence-free survival [BCRFS], clinical progression-free survival [CPFS], and castration-resistant prostate cancer-free survival [CRPCFS] were compared according to the combination of the pre-treatment predictors. RESULTS: The 5-year BCRFS, CPFS, and CRPCFS rates were 78.5, 91.7, and 94.4% respectively; there were two PCa deaths. Multivariate analysis revealed that the clinical T stage (cT3b and cT4) and Grade Group (GG) 5 status were independent risk factors for poor BCRFS, CPFS, and CRPCFS. In the GG ≤ 4 group, the Kaplan-Meier curves for BCRFS, CPFS, and CRPCFS revealed excellent outcomes. However, in the GG5 group, patients with cT3b and cT4 PCa evidenced significantly poorer oncological outcomes than those with cT3a PCa. CONCLUSION: The clinical T stage and GG status were significantly prognostic of oncological outcomes in patients with locally advanced PCa. In patients of GG ≤ 4 PCa, HDR-BT was effective even in patients with cT3b or cT4 PCa. However, in patients with GG5 PCa, careful monitoring is essential, particularly of patients with cT3b or cT4 PCa.

Epigenome-wide DNA methylation and transcriptome profiling of localized and locally advanced prostate cancer: Uncovering new molecular markers.

BACKGROUND: It has become increasingly important to identify molecular markers for accurately diagnosing prostate cancer (PCa) stages between localized PCa (LPC) and locally advanced PCa (LAPC). However, there is a lack of profiling both epigenome-wide DNA methylation and transcriptome for the same patients with PCa at different stages. This study aims to identify epitranscriptomic biomarkers screened in the peri-prostatic (PP) adipose tissue for predicting LPC and LAPC. METHODS: We profiled gene expression and DNA methylation of 10 PCa patients' PP adipose tissue (4 LPC and 6 LAPC). Differential analysis was used to identify differentially methylated CpG sites and expressed genes. An integrative analysis of the microarray gene expression profiles and DNA methylation profiles was conducted using LASSO (least absolute shrinkage and selection operator) between each studied gene and the CpG sites in their promoter region. This epitranscriptomic signature was constructed by combining the association and differential analyses. The signature was then refined using the genetic mutation data of >1500 primary PCa and metastasis PCa samples from 4 different studies. We determined genes that were the most significantly affected by mutations. Machine learning models were built to evaluate the classification ability of the identified signature using the gene expression profiles from three external cohorts. RESULTS: From the LASSO-based association analysis, we identified 56 genes presenting significant anti-correlation between the expression level and the methylation level of at least one CpG site in the promoter region (p-value<5 × 10-8). From the differential analysis, we detected 16,405 downregulated genes and 9485 genes containing at least one hypermethylated CpG site. We identified 30 genes that showed anti-correlation, down-regulation and hyper-methylation simultaneously. Using genetic mutation data, we determined that 6 of the 30 genes showed significant differences (adjusted p-value<0.05) in mutation frequencies between the primary PCa and metastasis PCa samples. The identified 30 genes performed well in distinguishing PCa patients with metastasis from PCa patient without metastasis (area under the receiver operating characteristic curve (AUC) = 0.81). The gene signature also performed well in distinguishing PCa patients with high risk of progression from PCa patients with low risk of progression (AUC = 0.88). CONCLUSIONS: We established an integrative framework to identify differentially expressed genes with an aberrant methylation pattern on PP adipose tissue that may represent novel candidate molecular markers for distinguishing between LPC and LAPC.

Comparative Outcomes of Robotic Radical Prostatectomy in Patients with Locally Advanced Prostate Cancer.

The effectiveness of radical prostatectomy alone for locally advanced prostate cancer is controversial owing to an increased complication rate and treatment-related morbidity. With technical advances and refinements in surgical techniques, robotic-assisted radical prostatectomy (RARP) has improved the outcomes of patients with locally advanced prostate cancer. RARP therefore plays a role in the treatment of locally advanced prostate cancer. In this study, we enrolled a total of 76 patients with pathologic stage pT3a, pT3b, pT4, or pN1. All patients were followed from surgery to June 2022, and their characteristics, perioperative outcomes, complications, adjuvant therapies and outcomes were analyzed. The median age of the patients was 69 years, and the initial PSA level was 20.5 (IQR 10.8-31.6) ng/mL. The median operative time was 205 (IQR 182-241) minutes. Sixty-six patients (86.8%) regained continence within 1 year, and the continence rate within 3 years of follow-up was 90.8% (69 patients). The overall survival rate was 100%. Twenty-two patients had BCR, of whom 13 received salvage androgen deprivation therapy (ADT), 2 received salvage external beam radiation therapy (EBRT) alone, and 7 received combined ADT and EBRT. No patient had disease progression to castration-resistant prostate cancer during a median 36 months of follow-up after salvage therapy. Our results suggest that RARP can also decrease tumor burden and allow for accurate and precise pathological staging with the need for subsequent treatment. Therefore, we recommend that RARP represents a well-standardized, safe, and oncologically effective option for patients with locally advanced prostate cancer.

Neoadjuvant treatment with androgen receptor signaling inhibitors prior to radical prostatectomy: a systematic review.

CONTEXT: There is an urgent need to develop novel treatment strategies in patients with unfavorable intermediate- and high-risk localized prostate cancer (PCa) to optimize the outcome of these patients. Androgen receptor signaling inhibitors (ARSI) have demonstrated a survival benefit in metastatic hormonesensitive and castration-resistant PCa. A similar benefit might be expected in the localized setting. OBJECTIVE: To perform a systematic review about the role of neoadjuvant ARSI in unfavorable intermediate and high-risk localized PCa. EVIDENCE ACQUISITION: We performed a systematic review of the following databases: MEDLINE (PubMed), EMBASE, Cochrane Library and Web of Science. Publications of ASCO were consulted to identify meeting abstract with early results of ongoing trials. This systematic review was performed and reported in accordance with the PRISMA guidelines. EVIDENCE SYNTHESIS: Pathological complete response (pCR) following neoadjuvant ARSI treatment was observed in 4%-13% of the patients. Minimal residual disease response ranged from 36% to 73.9% when defined as residual cancer burden < 0.25 cm3 at final pathology and from 8% to 20% when defined as the diameter of the remaining tumor < 5 mm. Despite intense neoadjuvant ARSI treatment, residual pT3 disease was observed in 48%-76% of the patients. In contrast, positive surgical margins (PSM) were present in only 5%-22%. Only one trial reported BCR following neoadjuvant ARSI therapy (44% BCR at a median follow-up of 4 years). CONCLUSION: Despite intense neoadjuvant ARSI therapy, pCR is rarely attained and high proportions of pT3 disease are still observed at final pathology. In contrast, promising results are obtained in terms of PSMs. Long-term survival outcomes are eagerly awaited.

Changes in treatment and mortality in men with locally advanced prostate cancer between 2000 and 2016: a nationwide, population-based study in Sweden.

OBJECTIVE: To evaluate whether the effects of radical treatment in men with locally advanced prostate cancer (PCa) on PCa mortality observed in randomised clinical trials are applicable on a population basis. PATIENTS AND METHODS: We conducted a population-based cohort study using the Prostate Cancer data Base Sweden of 20 350 men diagnosed between 2000 and 2016 with locally advanced PCa, defined as clinical local stage T3/T4, M0, Mx and a prostate-specific antigen level of <100 ng/mL. Cumulative PCa mortality was examined using competing risk analysis of all men with locally advanced PCa, and also including men who did not undergo radical treatment. Multivariate regression analysis, including prognostic factors, was used to calculate hazard ratios (HRs) for all-cause and PCa-specific death. RESULTS: The proportion of men treated with primary radical radiotherapy (n = 4174) or prostatectomy (n = 1210) increased from 15% in 2000-2003, 25% in 2004-2007, 33% in 2008-2011 to 43% in 2012-2016. The corresponding 5-year PCa mortality decreased from 19%, 18%, 17%, to 15% for all men, with the steepest decrease in men aged 65-74 years, from 16% to 8%. The risk of PCa mortality in men aged <80 years was lower in the last period compared to the first period, with a HR of 0.65 (95% confidence interval 0.56-0.76) in multivariate analysis. CONCLUSIONS: The threefold increase in use of radical treatment was accompanied by a modest decrease in PCa mortality in all men with newly diagnosed locally advanced PCa. For men aged 65-74 years, there was a 50% decrease in the relative risk of PCa death. This indicates that the benefits previously observed in randomised trials can also be achieved in a real-life setting.

Quality of life among patients after cystoprostatectomy as the treatment for locally advanced prostate cancer with bladder invasion.

PURPOSE: This study aimed to evaluate the changes of patients' quality of life (QoL) after cystoprostatectomy as a treatment for locally advanced prostate cancer (LAPC) with the bladder invasion and to determine risk factors for postoperative poor QoL. MATERIALS AND METHODS: Between Jan 2012 and December 2015, 27 patients who received cystoprostatectomy for LAPC with the bladder invasion were retrospectively included. QoL was assessed with the functional assessment of cancer therapy-prostate (FACT-P) questionnaire scores. Determinants for postoperative poor QoL were investigated using univariate and multivariate regression analysis. RESULTS: Three-year overall survival, biochemical progression-free survival, and clinical progress-free survival were 88.89%, 62.96% and 77.78%, respectively. Preoperative symptoms of hematuria, urinary frequency, and dysuria were well alleviated after cystoprostatectomy. Moreover, FACT-P questionnaire scores at 6 months and 1 year after cystoprostatectomy were significantly higher than preoperative scores. Univariate and multivariable analysis (p < .05) showed that postoperative complication was the independent risk factor for the loss of postoperative QoL. CONCLUSIONS: Patients' QoL can be improved after cystoprostatectomy as the treatment for LAPC with the bladder invasion, which is associated with ameliorative urinary symptoms after the surgery. Besides, surgical complication is identified to be a risk factor for postoperative poor QoL.

The role of cystoprostatectomy in management of locally advanced prostate cancer: a systematic review.

BACKGROUND: The role of cystoprostatectomy for the treatment of locally advanced prostate cancer (LAPC) was evaluated by a comprehensive review of contemporary literatures. METHODS: A systematic search of English language literatures using PubMed, EMBASE, Web of Science, and Cochrane library, from 1990 to 2018, was performed. Two independent authors reviewed abstracts as well as full-text articles and extracted data from the selected manuscripts. RESULTS: After the literature research, seven articles with a total of 211 patients were identified. Both 120 cases who received cystoprostatectomy for the primary treatment of LAPC and 91 cases for the salvage surgery after local recurrence were finally included. Overall incidence of positive surgical margins ranged from 25 to 78%. The incidence of major complications caused by the surgery during the follow-up time was limited. It had been reported that among LAPC patients who received cystoprostatectomy combined with adjuvant therapies, 5-year cancer-specific survival rate and 5-year biochemical progression-free survival was up to 87.1% and 62.2%. Moreover, symptoms such as hematuria and other urination dysfunctions, as well as patients' quality of life were significantly improved after cystoprostatectomy in LAPC patients with the bladder invasion. CONCLUSIONS: Cystoprostatectomy can serve as an alternative to the surgical step of multimodal therapy for highly selected LAPC patients with the bladder invasion, which may improve patients' symptoms and related quality of life. Therefore, cystoprostatectomy as an option for the treatment of LAPC with the bladder invasion may be feasible and safe with considerable survival outcomes.

Vasa nervorum angiogenesis in prostate cancer with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is generally accepted as a major route of cancer dissemination in malignancies associated with highly enervated organs. However, the effect of cancer cells on vasa nervorum remains unknown. We studied this effect in locally advanced prostate cancer, a high-risk feature associated with approximately 20% of prostate cancer specific mortality. METHODS: We used immunohistochemistry for CD34, fibroblast growth factor-2 (FGF-2), FSHR, podoplanin, vascular endothelial growth factor (VEGF), and VEGFR-2 as well as histochemical methods to examine the vasa nervorum of nerves invaded by cancer cells in tissue samples from 85 patients. RESULTS: The percentage of the nerve area occupied by CD34-positive vasa nervorum endothelial cells in nerves with PNI was much higher than in nerves without PNI (7.3 ± 1.2 vs 1.9 ± 0.4; P < 0.001 and 5.8 ± 0.6 vs 1.23 ± 0.8; P < 0.001 in pT3a and pT3b prostate cancer specimens, respectively). In 19/85 of the patients the CD34-positive vasa nervorum microvessels have a thick basement membrane, similar to the vessels in diabetic microangiopathy. This subendothelial layer contains collagen fibers. Vasa nervorum endothelia and Schwann cells express FGF-2 (nuclear localization) and FSHR (plasma membrane and cytoplasmic staining). Prostate cancer cells invading nerves express VEGF, a critical cytokine in tumor angiogenesis. The vasa nervorum of prostatic nerves with PNI did not express detectable levels of VEGFR-2. No podoplanin-positive lymphatic vessels were seen in nerves. CONCLUSION: In locally advanced prostate cancer, PNI of cancer cells is associated with formation of new endoneurial capillaries and changes of vasa nervorum morphology.

Elderly patients aged ≥ 75 years with locally advanced prostate cancer may benefit from local treatment: a population-based propensity score-adjusted analysis.

OBJECTIVE: To evaluate whether elderly patients aged ≥ 75 years with locally advanced prostate cancer (LAPC) may benefit from local treatment (LT). METHODS: Elderly patients aged ≥ 75 years with non-metastatic cT3-4 LAPC who were treated with LT [radical prostatectomy (RP), radiation therapy (RT)] or non-LT (NLT) were identified. After propensity score matching (PSM), cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were assessed. In the assessment of LT vs. NLT and RP vs. RT, multivariable competing risk regression (MVA CRR) analysis was used. RESULTS: 368 and 482 paired patients were matched for LT vs. NLT and RP vs. RT, respectively. 5 and 10 years CSM rates were 9.4 vs. 18.5% in LT and 24.9 vs. 29.3% in NLT-treated patients, respectively (P < 0.0001). 5 and 10 years CSM rates were 3.4% vs. 8.6% in RP and 6.7% vs. 15.1% in RT-treated patients, respectively (P = 0.10). In the MVA CRR model, after PSM, NLT resulted in higher CSM rates in Gleason score 8-10 [subhazard ratio (sHR) = 2.83, P < 0.001], cT3b/4 (sHR = 3.97/2.56, P = 0.003/0.002), cN0 (sHR = 2.52, P < 0.001) or PSA > 10 ng/ml [sHR (PSA = 10.1-20 ng/ml) = 4.59, P = 0.03; sHR (PSA > 20 ng/ml) = 2.77, P = 0.001] patients compared with LT. However, no statistically significant difference in CSM was observed between RP and RT, except for cT3a patients in whom higher CSM rates were noted for RT compared with RP (sHR = 3.91, P = 0.02). CONCLUSION: LAPC patients may benefit from local treatment despite advanced age. However, this benefit was only seen in patients with cT3b/4, Gleason score 8-10, cN0 or PSA > 10 ng/ml.

[Use of multiparametric magnetic resonance imaging in t-staging of prostate cancer: a multicenter study].

AIM: The study aimed to analyze the diagnostic performance of preoperative multiparametric magnetic resonance imaging (mp-MRI) in the staging of prostate cancer (PCa) versus postoperative histological examination and determine the most sensitive pulse sequence from the mp-MRI protocol in estimating the local extent of PCa. MATERIALS AND METHODS: The study comprised 112 men aged 52 to 84 years with a morphologically verified diagnosis of prostate cancer. All patients underwent pelvic mp-MRI before radical prostatectomy (RPE) no earlier than six weeks after the prostate biopsy. Radical prostatectomy was performed within two weeks after mp-MRI. MP-MRI findings and the results of postoperative histology were compared using a binary logistic regression model. RESULTS: The sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative (NPV) predictive values for predicting extracapsular extension were 87.5, 92.6, 91, 84 and 94.3%, respectively; for predicting seminal vesicles invasion, they were 85, 95, 90, 80.9 and 96.7%, respectively. When stratified by the presence or absence of the pseudocapsule invasion, the reliability of detecting the tumor spread for different types of images decreases in the following order: DWI - T2 + DWI - T2 VI - DCE-MRI. CONCLUSION: mp-MRI has high sensitivity, specificity, general diagnostic accuracy, high NPV, and PPV values in detecting an extracapsular extension of prostate cancer. According to the binary logistic regression model, the greatest contribution to the decision on the presence or absence of extracapsular extension is also made by the DWI.

Outcome predictors of radical cystectomy in patients with cT4 prostate cancer: a multi-institutional study of 62 patients.

OBJECTIVES: To identify which patients with macroscopic bladder-infiltrating T4 prostate cancer (PCa) might have favourable outcomes when treated with radical cystectomy (RC). MATERIALS AND METHODS: We evaluated 62 patients with cT4cN0-1 cM0 PCa treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan-Meier method and log-rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression-free, PCa-specific and overall survival. RESULTS: Of the 62 patients, 19 (30.6%) did not have clinical progression during follow-up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PCa and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis-free at last follow-up was 86 (1-314) months, 8/19 patients had a follow-up of >5 years, and five patients survived metastasis-free for >15 years. Patients without seminal vesicle invasion (SVI) had the best outcomes, with an estimated 10-year PCa-specific survival of 75% compared with 24% for patients with SVI. CONCLUSION: For cT4 PCa RC can be an appropriate treatment for local control and part of a multimodality-treatment approach. Although recurrences are probable, these do not necessarily translate into cancer-specific death. Men without SVI had a 75% 10-year PCa-specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment.

Long-term outcomes of intensity-modulated radiation therapy combined with neoadjuvant androgen deprivation therapy under an early salvage policy for patients with T3-T4N0M0 prostate cancer.

BACKGROUND: Long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) androgen deprivation therapy (ADT) under an early salvage policy in patients with locally advanced prostate cancer (LAPC) were evaluated. METHODS: Data from 120 patients with T3-T4N0M0 adenocarcinoma of the prostate treated with IMRT were analyzed. NA-ADT with a median duration of 6 months was provided in all cases. Seventy-eight Gy, at 2 Gy per fraction, was delivered to the prostate and seminal vesicles. Adjuvant ADT (A-ADT) was not provided for any patient following the completion of IMRT. Salvage ADT (S-ADT) commenced when PSA values >4 ng/ml. RESULTS: The median follow-up period was 97 months. S-ADT was initiated in 39 patients. The median PSA value at the initiation of S-ADT was 5.7 ng/ml. The 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival and S-ADT-free rates were 53.2 % [95 % confidence interval (CI) 43.4, 62.1], 96.6 % (95 % CI 91.2, 98.7), 89.1 % (95 % CI 81.5, 93.7) and 66.6 % (95 % CI 60, 74.6), respectively. The estimated 8-year cumulative incidence rates of grade 2-3 late gastrointestinal, and grade 2-3 genitourinary toxicity were 7.6 and 10.7 %, respectively. No grade 4 toxicity was observed. CONCLUSIONS: High-dose IMRT, combined with NA-ADT for LAPC, was associated with favorable long-term disease-specific and overall survival outcomes, despite non-provision of A-ADT under the early S-ADT provision policy. This approach may represent a viable alternative to uniform provision of long-term A-ADT, because two-thirds of the patients maintained ADT-free status over an 8-year period after IMRT. Prospective trials will be required.

Radiation Therapy for Locally Advanced Prostate Cancer: How Do We Treat Patients with cN1 Disease?

Radiotherapy (RT) for high-risk localized prostate cancer (HRLPC) can be controversial in the context of increasing detection of suspicious lymph nodes via advanced imaging techniques. The EORTC 22683 trial initially established RT with androgen deprivation therapy (ADT) as the standard of care for HRLPC, but many patients remain uncured. GETUG-AFU-12 showed that addition of docetaxel and estramustine to ADT improved relapse-free survival but not overall survival. STAMPEDE later demonstrated that abiraterone acetate with ADT and RT significantly improved failure-free survival and overall survival. Ongoing trials such as ENZARAD, ATLAS, DASL-HiCap, and GETUG-P17 ALADDIN are investigating the efficacy of new androgen receptor pathway inhibitors combined with RT and ADT. These studies aim to refine treatment strategies for HRLPC, particularly in the context of advanced imaging and patient upstaging. PATIENT SUMMARY: Addition of newer medications to standard radiation therapy has shown promise in improving survival for men with high-risk prostate cancer. Ongoing studies are testing these options to find the best combination. The aim is to increase the chances of curing prostate cancer, especially as advanced scan techniques are detecting more cases.

Multivariate logistic regression analysis of the clinical factors influencing locally advanced prostate cancer.

Background: Locally advanced prostate cancer (PCa) carries a high risk of recurrence and metastasis after surgery, and the prognosis is poor. We explored the risk factors for locally advanced PCa among clinical factors (neutrophil: lymphocyte ratio, lymphocyte: monocyte ratio) and indicators of systemic inflammation [prostate-specific antigen (PSA) level, Gleason score, body mass index (BMI)] through retrospective evaluation of patients with PCa diagnosed at our center. The pathologic T stage was a key indicator of locally advanced PCa. Methods: Data from patients with pathologically confirmed PCa at our center from 1 January 2015 to 1 May 2020 were collected in strict accordance with inclusion and exclusion criteria. Clinical data were collected and the relationship between the indicators and the pathologic T stage was explored. First, Spearman rank correlation analysis was used to find the correlates of the pathologic T stage. Then, logistic ordered multiple regression analysis was used to identify independent risk factors. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy for the T stage of PCa. Results: After rigorous screening, the data of 177 patients were obtained. Spearman correlation analysis showed that BMI, the PSA level, Gleason score, hypertension, N stage, and M stage were significantly correlated with the T stage (P<0.05), suggesting that these factors may be involved in locally advanced PCa. Analyses of ROC curves showed that the PSA level [area under the ROC curve (AUC) =0.802] had greater value than BMI (0.675) for the diagnosis of the pathologic T stage PCa, and that a combination of BMI and PSA (combined AUC =0.822) could improve locally advanced PCa diagnosis. Conclusions: BMI and PSA are independent risk factors for locally advanced PCa. They may play a key part in locally advanced PCa.

Perception of cure in prostate cancer: human-led and artificial intelligence-assisted landscape review and linguistic analysis of literature, social media and policy documents.

BACKGROUND: Understanding stakeholders' perception of cure in prostate cancer (PC) is essential to preparing for effective communication about emerging treatments with curative intent. This study used artificial intelligence (AI) for landscape review and linguistic analysis of definition, context and value of cure among stakeholders in PC. MATERIALS AND METHODS: Subject-matter experts (SMEs) selected cure-related key words using Elicit, a semantic literature search engine, and extracted hits containing the key words from Medline, Sermo and Overton, representing academic researchers, health care providers (HCPs) and policymakers, respectively. NetBase Quid, a social media analytics and natural language processing tool, was used to carry out key word searches in social media (representing the general public). NetBase Quid analysed linguistics of key word-specific hit sets for key word count, geolocation and sentiments. SMEs qualitatively summarised key word-specific insights. Contextual terms frequently occurring with key words were identified and quantified. RESULTS: SMEs identified seven key words applicable to PC (number of acquired hits) across four platforms: Cure (12429), Survivor (6063), Remission (1904), Survivorship (1179), Curative intent (432), No evidence of disease (381) and Complete remission (83). Most commonly used key words were Cure by the general public and HCPs (11815 and 224 hits), Survivorship by academic researchers and Survivor by policymakers (378 hits each). All stakeholders discussed Cure and cure-related key words primarily in early-stage PC and associated them with positive sentiments. All stakeholders defined cure differently but communicated about it in relation to disease measurements (e.g. prostate-specific antigen) or surgery. Stakeholders preferred different terms when discussing cure in PC: Cure (academic researchers), Cure rates (HCPs), Potential cure and Survivor/Survivorship (policymakers) and Cure and Survivor (general public). CONCLUSION: This human-led, AI-assisted large-scale qualitative language-based research revealed that cure was commonly discussed by academic researchers, HCPs, policymakers and the general public, especially in early-stage PC. Stakeholders defined and contextualised cure in their communications differently and associated it with positive value.

Influential Factors Impacting Treatment Decision-making and Decision Regret in Patients with Localized or Locally Advanced Prostate Cancer: A Systematic Literature Review.

CONTEXT: Treatment decision-making (TDM) for patients with localized (LPC) or locally advanced (LAPC) prostate cancer is complex, and post-treatment decision regret (DR) is common. The factors driving TDM or predicting DR remain understudied. OBJECTIVE: Two systematic literature reviews were conducted to explore the factors associated with TDM and DR. EVIDENCE ACQUISITION: Three online databases, select congress proceedings, and gray literature were searched (September 2022). Publications on TDM and DR in LPC/LAPC were prioritized based on the following: 2012 onward, ≥100 patients, journal article, and quantitative data. The Preferred Reporting Items Reviews and Meta-analyses guidelines were followed. Influential factors were those with p < 0.05; for TDM, factors described as "a decision driver", "associated", "influential", or "significant" were also included. The key factors were determined by number of studies, consistency of evidence, and study quality. EVIDENCE SYNTHESIS: Seventy-five publications (68 studies) reported TDM. Patient participation in TDM was reported in 34 publications; overall, patients preferred an active/shared role. Of 39 influential TDM factors, age, ethnicity, external factors (physician recommendation most common), and treatment characteristics/toxicity were key. Forty-nine publications reported DR. The proportion of patients experiencing DR varied by treatment type: 7-43% (active surveillance), 12-57% (radical prostatectomy), 1-49% (radiotherapy), 28-49% (androgen-deprivation therapy), and 21-47% (combination therapy). Of 42 significant DR factors, treatment toxicity (sexual/urinary/bowel dysfunction), patient role in TDM, and treatment type were key. CONCLUSIONS: The key factors impacting TDM were physician recommendation, age, ethnicity, and treatment characteristics. Treatment toxicity and TDM approach were the key factors influencing DR. To help patients navigate factors influencing TDM and to limit DR, a shared, consensual TDM approach between patients, caregivers, and physicians is needed. PATIENT SUMMARY: We looked at factors influencing treatment decision-making (TDM) and decision regret (DR) in patients with localized or locally advanced prostate cancer. The key factors influencing TDM were doctor's recommendation, patient age/ethnicity, and treatment side effects. A shared, consensual TDM approach between patients and doctors was found to limit DR.

Super-Selective Trans-Catheter Arterial Embolization (TAE) of the Vesical Arteries in the Management of Intractable Hematuria Secondary to Advanced Bladder and Prostate Cancers.

This article was previously presented as an abstract at the 18th UAA Congress, Seoul, October 15-17, 2020, and the abstract was published in The International Journal of Urology. It was also presented as an e-poster at the 2021 BAUS Annual Meeting on June 22, 2021. Introduction In frail patients intractable hematuria secondary to advanced pelvic malignancies is a clinical challenge. Super-selective TAE of the vesical arteries is a suitable minimally invasive option. We present our experience in this patient cohort. Patients and methods All patients who underwent TAE from January 2014 to December 2019 were included. Super-selective TAE of the superior and inferior vesical arteries was done using 300-500µ polyvinyl alcohol (PVA) particles. Demographic data, cancer stage, associated urinary system obstruction, pre-embolization palliative treatment, chemotherapy, and radiotherapy were recorded. Technical and clinical success, time to cessation of hematuria, recurrence of hematuria, and complications were recorded. Data are presented as mean ± standard deviation, and statistical significance is set at p<0.05. Results From 2014 to 2019, seven patients underwent eight procedures. The average patient's age was 60.6±10.3 years. All presented with gross hematuria, six due to locally advanced and/or metastatic bladder cancer, and one due to prostate cancer. The average time of hematuria clearance was 60 hours. The average hemoglobin levels at the time of the procedure, one month, and six months post-embolization were 9.6±1.7 g/dL, 10.6±1.5 g/dL (p<0.05), and 9.6±0.9 g/dL, respectively (p>0.05). Packed red blood cell (PRBC) requirements decreased from 7±2 units to 5±3 units after the procedure (p >0.05). The patients were followed up for an average of 13.6 months and four had a recurrence at an average of four months post-embolization. Conclusion Super-selective TAE is an effective palliative method in controlling intractable hematuria. The risks of major surgery and anesthesia are omitted, and the procedure can be repeated as needed. Furthermore, post-embolization complications, using this technique, are minor and manageable.

Impact of prostate radiotherapy on survival outcomes in clinically node-positive prostate cancer: A multicentre retrospective analysis.

PURPOSE: To evaluate clinical outcomes for cN1M0 prostate cancer treated with varied modalities. MATERIALS AND METHODS: Men with radiological stage cN1M0 prostate cancer on conventional imaging, treated from 2011-2019 with various modalities across four centres in the UK were included. Demographics, tumour grade and stage, and treatment details were collected. Biochemical and radiological progression-free survival (bPFS, rPFS) and overall survival (OS) were estimated using Kaplan Meier analyses. Potential factors impacting survival were tested with univariable log-rank test and multivariable Cox-proportional hazards model. RESULTS: Total 337 men with cN1M0 prostate cancer were included, 47% having Gleason grade group 5 disease. Treatment modalities included androgen deprivation therapy (ADT) in 98.9% men, either alone (19%) or in combinations including prostate radiotherapy (70%), pelvic nodal radiotherapy (38%), docetaxel (22%), or surgery (7%). At median follow up of 50 months, 5-year bPFS, rPFS, and OS were 62.7%, 71.0%, and 75.8% respectively. Prostate radiotherapy was associated with significantly higher bPFS (74.1% vs 34.2%), rPFS (80.7% vs 44.3%) and OS (86.7% vs 56.2%) at five years (log rank p < 0.001 each). On multivariable analysis including age, Gleason grade group, tumour stage, ADT duration, docetaxel, and nodal radiotherapy, benefit of prostate radiotherapy persisted for bPFS [HR 0.33 (95% CI 0.18-0.62)], rPFS [HR 0.25 (0.12-0.51)], and OS [HR 0.27 (0.13-0.58)] (p < 0.001 each). Impact of nodal radiotherapy or docetaxel was not established due to small subgroups. CONCLUSION: Addition of prostate radiotherapy to ADT in cN1M0 prostate cancer yielded improved disease control and overall survival independent of other tumour and treatment factors.