Localized Prostate Research Articles

Hospital-Level Variability in the Adoption of Image-Guided Focal Therapy for Localized Prostate and Kidney Cancer

BackgroundFocal therapy, a minimally invasive procedure, offers targeted treatment for kidney and prostate cancer using image guidance. However, the current institutional landscape of its adoption in localized prostate and kidney cancer remains less understood. This analysis compares its usage between the 2 cancers to discern health system determinants affecting the adoption of these treatments. MethodsThe study used data from adult patients with localized prostate and kidney cancer from the National Cancer Database. We calculated adjusted probabilities of focal therapy usage per facility via multivariable mixed-effects logistic regression model with hospital-level random effects. We analyzed interhospital variability through ranked caterpillar plots and Spearman correlation coefficient. ResultsAmong 1,559,334 prostate and 425,753 kidney cancer patients, 1.6% and 6.3% received focal therapy, respectively. The interhospital variation ranged from 0.13% to 32.17% for prostate cancer and 1.16% to 30.48% for kidney cancer. The hospital-level odds of focal therapy for prostate and kidney cancer were weakly correlated (Spearman's ρ = 0.21; P < .001). ConclusionsOur analysis revealed a substantial hospital-level discrepancy in the utilization of focal therapy. Despite this, there was a limited correlation between the use of focal therapy for these two types of cancer within the same hospital. Our findings emphasize the presence of multifaceted factors influencing the adoption of focal therapy, both at facility and healthcare system levels.

Comparative analysis of treatment decision-making in patients with localized prostate and cervical cancer: what influences receiving surgery or radiotherapy?

PurposeThis study focused on identifying the factors influencing the decision-making process in patients with localized prostate and cervical cancer in Japan and specifically examining the choice between surgery and radiotherapy.MethodsPatients with specific cancer stages registered with a healthcare research company for whom radical surgery or radiotherapy was equally effective and recommended participated in this cross-sectional online survey.ResultsThe responses of 206 and 231 patients with prostate and cervical cancer, respectively, revealed that both groups relied heavily on the physicians’ recommendations (prostate: odds ratio (OR) = 40.3, p < 0.001; cervical: OR = 5.59, p < 0.001) and their impression of radiotherapy (prostate: OR = 9.22, p < 0.001; cervical: OR = 2.31, p < 0.001). Factors such as hypertension (OR = 6.48, p < 0.05), diabetes mellitus (OR = 9.68, p < 0.05), employment status (OR = 0.08, p < 0.01), and impressions of surgery (OR = 0.14, p < 0.01) also played a significant role in patients with prostate cancer. In contrast, the specialty of the physician (OR = 4.55, p < 0.05) proposing the treatment influenced the decision-making process of patients with cervical cancer. Information sources varied between the two groups: patients with prostate cancer were more inclined towards printed materials, whereas patients with cervical cancer were more inclined towards interpersonal relationships.ConclusionAlthough several limitations, such as the sample and recall bias, were noted, this study emphasizes the role of psychosocial factors in the decision-making process and the requirement for tailored information sources.

An open-source nnU-net algorithm for automatic segmentation of MRI scans in the male pelvis for adaptive radiotherapy.

Adaptive MRI-guided radiotherapy (MRIgRT) requires accurate and efficient segmentation of organs and targets on MRI scans. Manual segmentation is time-consuming and variable, while deformable image registration (DIR)-based contour propagation may not account for large anatomical changes. Therefore, we developed and evaluated an automatic segmentation method using the nnU-net framework. The network was trained on 38 patients (76 scans) with localized prostate cancer and tested on 30 patients (60 scans) with localized prostate, metastatic prostate, or bladder cancer treated at a 1.5 T MRI-linac at our institution. The performance of the network was compared with the current clinical workflow based on DIR. The segmentation accuracy was evaluated using the Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) metrics. The trained network successfully segmented all 600 structures in the test set. High similarity was obtained for most structures, with 90% of the contours having a DSC above 0.9 and 86% having an MSD below 1mm. The largest discrepancies were found in the sigmoid and colon structures. Stratified analysis on cancer type showed that the best performance was seen in the same type of patients that the model was trained on (localized prostate). Especially in patients with bladder cancer, the performance was lower for the bladder and the surrounding organs. A complete automatic delineation workflow took approximately 1 minute. Compared with contour transfer based on the clinically used DIR algorithm, the nnU-net performed statistically better across all organs, with the most significant gain in using the nnU-net seen for organs subject to more considerable volumetric changes due to variation in the filling of the rectum, bladder, bowel, and sigmoid. We successfully trained and tested a network for automatically segmenting organs and targets for MRIgRT in the male pelvis region. Good test results were seen for the trained nnU-net, with test results outperforming the current clinical practice using DIR-based contour propagation at the 1.5 T MRI-linac. The trained network is sufficiently fast and accurate for clinical use in an online setting for MRIgRT. The model is provided as open-source.

Elevated periprostatic venous testosterone correlates with prostate cancer progression after radical prostatectomy.

BACKGROUNDGenerally, clinical assessment of gonadal testosterone (T) in human physiology is determined using concentrations measured in peripheral blood. Prostatic T exposure is similarly thought to be determined from peripheral T exposure. Despite the fact that androgens drive prostate cancer, peripheral T has had no role in the clinical evaluation or treatment of men with localized prostate cancer.METHODSTo assess the role of local androgen delivery in prostate cancer, we obtained blood from the (periprostatic) prostatic dorsal venous complex in 266 men undergoing radical prostatectomy from July 2014 to August 2021 and compared dorsal T (DT) levels with those in circulating peripheral blood (PT) and prostatic tissue. Comprehensive targeted steroid analysis and unbiased metabolomics analyses were performed. The association between the DT/PT ratio and progression-free survival after prostatectomy was assessed.RESULTSSurprisingly, in some men, DT levels were enriched several-fold compared with PT levels. For example, 20% of men had local T concentrations that were at least 2-fold higher than peripheral T concentrations. Isocaproic acid, a byproduct of androgen biosynthesis, and 17-OH-progesterone, a marker of intratesticular T, were also enriched in the dorsal vein of these men, consistent with testicular shunting. Men with enriched DT had higher rates of prostate cancer recurrence. DT/PT concentration ratios predicted worse outcomes even when accounting for known clinical predictors.CONCLUSIONSThese data suggest that a large proportion of men have a previously unappreciated exposure to an undiluted and highly concentrated T supply. Elevated periprostatic T exposure was associated with worse clinical outcomes after radical prostatectomy.FUNDINGNational Cancer Institute (NCI), NIH grants R01CA172382, R01CA236780, R01CA261995, R01CA249279, and R50CA251961; US Army Medical Research and Development Command grants W81XWH2010137 and W81XWH-22-1-0082.

PD20-07 ASSOCIATIONS BETWEEN PATIENT SOCIODEMOGRAPHIC FACTORS AND RISK-APPROPRIATE PROSTATE CANCER MANAGEMENT

You have accessJournal of UrologyCME1 Apr 2023PD20-07 ASSOCIATIONS BETWEEN PATIENT SOCIODEMOGRAPHIC FACTORS AND RISK-APPROPRIATE PROSTATE CANCER MANAGEMENT Madison Novosel, Shayan Smani, Victoria Marks, Farah Jeong, Preston Sprenkle, and Michael Leapman Madison NovoselMadison Novosel More articles by this author , Shayan SmaniShayan Smani More articles by this author , Victoria MarksVictoria Marks More articles by this author , Farah JeongFarah Jeong More articles by this author , Preston SprenklePreston Sprenkle More articles by this author , and Michael LeapmanMichael Leapman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003286.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although definitive treatment is associated with improved survival for aggressive prostate cancer, a significant number of patients do not receive treatment. To identify gaps in practice, we sought to evaluate sociodemographic factors associated with non-treatment by clinical risk strata in the contemporary era. METHODS: We performed a retrospective study of patients with prostate cancer using the National Cancer Database. A total of 954,591 patients diagnosed with localized prostate (cT1-4N0M0) cancer from 2010 to 2020 were included in the analysis. We used descriptive statistics and multivariable logistic regression to evaluate factors associated with non-treatment, stratifying analyses by D’Amico clinical risk criteria. RESULTS: The mean patient age at diagnosis was 65 years. Overall, 26.0% were diagnosed with low, 43.4% with intermediate, and 30.6% with high-risk prostate cancer. There were 131,122 (13.7%) who did not undergo initial treatment, including 82,318 (62.8%) with low, 35,499 (27.1%) with intermediate, and 13,305 (10.2%) with high-risk disease. The proportion of patients not receiving treatment increased over time in all risk groups between 2010 and 2010, including among low (11.7% versus 59.5%), intermediate (4.5% versus 12.5%) and high risk (3.6% versus 5.1%) disease. Compared with White patients, Black patients had lower odds of definitive treatment. This effect was more pronounced for patients with high (OR 0.61, 95% CI 0.58-0.64) rather than intermediate (OR 0.76, 95% CI 0.73-0.78) risk prostate cancer. Asian patients had lower odds of treatment compared with White patients across all disease risk strata (OR 0.84, 95% CI 0.80-0.88) but not high-risk disease (OR 0.90, 95% CI 0.80-1.00). There were lower odds of treatment among American Native/Alaskan Native versus White patients but not for high-risk disease (OR 0.79, 95% CI 0.57-1.10) Uninsured (OR 0.45, 95% CI 0.42-0.47, p<0.001), and Medicaid-insured (OR 0.68, 95% CI 0.66-0.71, p<0.001) patients were less likely to be treated overall. Patients residing in higher income areas had lower odds of over-treatment for low-risk prostate cancer (OR 0.84, 95% CI 0.81-0.87) and higher odds of treatment for high-risk prostate cancer (OR 1.34, 95% CI 1.25-1.44). CONCLUSIONS: Among patients diagnosed with prostate cancer in the contemporary era race and insurance are significantly associated with non-treatment for aggressive prostate cancer. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e586 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Madison Novosel More articles by this author Shayan Smani More articles by this author Victoria Marks More articles by this author Farah Jeong More articles by this author Preston Sprenkle More articles by this author Michael Leapman More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract 1438: Organic anion transporter(SLCO)genotype and prostate cancer progression: Prospective cohort study and meta-analysis

Abstract Background: Organic anion-transporting polypeptides, encoded by SLCO genes, have multiple substrates, including androgens. Genotype and protein levels moderate the uptake of androgens into prostate cells, a process competitively inhibited in vitro by statin medications. Single-nucleotide polymorphisms (SNPs) in SLCO2B1 influence SLCO1B2 expression and efficacy of androgen uptake in vitro. Methods: Among men of self-reported European ancestry diagnosed with prostate cancer during prospective follow-up of the Health Professionals Follow-up Study (HPFS, diagnosed 1986-2017) and the Physicians’ Health Study (PHS, 1982-2010) combined, we evaluated four SLCO2B1 SNPs identified in prior studies and time from diagnosis to lethal disease (metastases/prostate cancer-specific death), adjusting for age, calendar year of diagnosis, and principal components of genetic variation to account for local ancestry. We also conducted a systematic review and harmonized allele coding in prior studies for a two-stage dose-response meta-analysis with additive allele coding. Results: Of the 3208 men in the prospective cohort study, 96% were diagnosed with clinically localized (T1/T2) prostate cancer. Most were treated with radical prostatectomy (47%) or radiation (36%); 33% ever received androgen deprivation therapy (ADT). Over up to 32 years of follow-up (median, 14.4 years), 382 lethal events occurred. The intronic SNP rs1077858 had the strongest association with lethal disease (hazard ratio [HR] per minor allele 1.14, 95% confidence interval [CI] 0.98-1.33). Data were suggestive of potential differences for the four SNPs by use of statins and ADT but were not conclusive. The systematic review identified 2 additional population-based studies of primary disease and 4 hospital-based studies of advanced disease, none of which studied effect modification by statins or ADT. Among these 2377 men, 1088 events of recurrence, metastasis, or prostate cancer death occurred. In a meta-analysis of all 7 studies, the genotype of the exonic SNP rs12422149 (minor allele frequency 15%) that results in lower androgen uptake was associated with better outcomes (HR per minor allele 0.80, 95% CI 0.69-0.93), with little between-study heterogeneity (I2 0.27). For the intronic SNP rs1077858, the genotype with higher SLCO2B1 mRNA expression was associated with worse outcomes (HR per minor allele 1.14, 95% CI 0.99-1.31, 3 studies with I2 0.68). Conclusion: These results are compatible with the hypothesis that inherited genetic variation in SLCO2B1 influences androgen uptake and prostate cancer prognosis. These and other genetic variants, together with clinical features, may have potential utility as predictive biomarkers for identifying men with prostate cancer who might benefit from early therapy beyond ADT. Whether adjuvant statin therapy could mitigate the inherited risk requires further study. Citation Format: Konrad H. Stopsack, Harisha Rajanala, Anna Plym, Jane B. Vaselkiv, Konstantina Matsoukas, Ericka M. Ebot, Sarah C. Markt, Kathryn L. Penney, Gwo-Shu M. Lee, Lorelei A. Mucci, Philip W. Kantoff. Organic anion transporter(SLCO)genotype and prostate cancer progression: Prospective cohort study and meta-analysis [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 1438.

Abstract 20: Cancer incidence in the U.S. military: An updated analysis

Abstract Background: Active duty military service members and the general US population differ in several ways related to cancer occurrence. This study aimed to update and expand our previous study which compared incidence of six cancers between the U.S. military and general populations. Methods: Cancers included in this study were pathologically confirmed malignant lung, colorectal, testicular, prostate, cervical and breast tumors diagnosed 1990-2013. The study populations were men and women aged 20-59 in the US active duty military and the population in nine areas covered by the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registry program. Military data were from the Department of Defense’s Automated Central Tumor Registry (ACTUR) and Defense Manpower Data Center. Age adjusted rates in ACTUR and SEER and incidence rate ratios (IRR) and 95% confidence intervals (95% CI) comparing ACTUR to SEER were calculated. Comparisons were made by sex, race, and cancer stage. Results: Age adjusted incidence rates of colorectal cancer were significantly lower in ACTUR than SEER among White (IRR 0.78; 95% CI 0.72-0.84) and Black men (IRR 0.86; 95% CI 0.74-1.00), respectively. Lung cancer incidence was lower in ACTUR than SEER among White (IRR 0.55; 95% CI 0.49-0.62) and Black men (IRR 0.34; 95% CI 0.26-0.42) and White women (IRR 0.74; 95% CI 0.53-0.98). Whites in ACTUR had significantly lower incidence of testicular cancer (IRR 0.92; 95% CI 0.88-0.96). Lower incidence of cervical cancer in ACTUR was observed among both Whites (IRR 0.82; 95% CI 0.69-0.97) and Blacks (IRR 0.39; 95% CI 0.27-0.54). Incidence of prostate cancer was higher in ACTUR than SEER among both Whites (IRR 2.31; 95% CI 2.18-2.45) and Blacks (IRR 2.35; 95% CI 2.13-2.58). Results by tumor stage showed similar results between the ACTUR and SEER populations for regional and distant tumors, while no differences between the two were observed for localized tumors, except in the case of prostate cancer. Incidence of localized and regional prostate tumors was higher in ACTUR than SEER, while there was no significant difference in distant tumors. Conclusion: Active duty service members had lower age adjusted incidence rates of colorectal, lung, testicular, and cervical cancers, but higher rates of prostate cancer than the general US population. While these findings may result from the combined effects of many factors, the lower incidence in the military may be associated with healthier status of service members. In addition, universal health care for active duty military may lead to earlier diagnosis of some tumors, such as prostate cancer, in the military. Disclaimer: The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of USUHS, HJF, the DoD or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products or organizations does not imply endorsement by the US Government. Citation Format: Julie A. Bytnar, Katherine A. McGlynn, Craig D. Shriver, Kangmin Zhu. Cancer incidence in the U.S. military: An updated analysis [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 20.

Abstract 5860: Five-year survival of patients with late stage prostate cancer: Comparison of the military health system with the US general population

Abstract While the five-year survival for local and regional prostate cancer is nearly 100%, it decreases dramatically for advanced (stages III and IV) prostate cancer. Access to health care is an important factor that affects cancer prognosis. The Military Health System (MHS) provides universal health care to beneficiaries. However, it is unclear whether the universal care translates into improved survival among patients with advanced prostate cancer. We compared survival of patients with advanced prostate cancer between the MHS and the U.S. general population. The MHS patients (N= 5,379) were identified from the Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR). Patients in the U.S. general population (N=21,516) were identified from the Surveillance, Epidemiology, and End Results (SEER) program. All patients were diagnosed between January 1, 1987 and December 31, 2013. The two populations were matched on age (within 5 years), race, and diagnosis year. Multivariable Cox regression hazard model was used to estimate hazard ratios (HRs) for ACTUR compared to SEER. ACTUR patients exhibited longer 5-year survival than matched SEER patients (HR=0.74, 95% CI=0.67-0.83), after adjustment for the potential confounders. In stratified analysis, the improved survival was observed for ages 50 years or older, both white and black races, all tumor stages, and grades. In stratified analysis by treatment receipt, the improved survival of ACTUR patients compared to SEER patients remained regardless of the receipt of surgery or radiation treatment. Our results suggested that MHS beneficiaries with advanced prostate cancer had longer survival than their counterparts in the U.S. general population. Universal health care in the MHS might translate into improved survival for advanced prostate cancer. Disclaimers: The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions, or policies of the USUHS, HJF, the DoD or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Jie Lin, Darryl Nousome, Jiji Jiang, Gregory Chesnut, Craig Shriver, Kangmin Zhu. Five-year survival of patients with late stage prostate cancer: Comparison of the military health system with the US general population [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 5860.

Cohort study of patients with oligorecurrent prostate cancer: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.

5009 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligo-recurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions from PCa metastases could be removed in 343 (94.2%) patients. Within three months from surgery, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 225 patients experienced BCR and 121 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 10.8 months and 10.3 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.5) and 35.5 months (25.9-45.9 months). At two years of follow-up, BFS rate was 31.9% and TFS rate was 58.0%. In multivariable analyses, higher preoperative PSA (HR: 1.1), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.9), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligo-recurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligo-recurrent PCa.

The evolving landscape of practice pattern and survival outcomes in the management of localized low-risk prostate cancer.

e17057 Background: The majority of patients with low-risk prostate cancer (LRPC) are candidates for active surveillance (AS) or definitive local treatment, which may include radical prostatectomy (RP), external beam radiotherapy (EBRT), or prostate seed implant (PSI). In the recent edition of the National Comprehensive Cancer Network (NCCN) guidelines, the “preferred” status was removed for AS, which rekindled a debate and interest in the management of LRPC. In this study, we analyzed the treatment pattern and impact of various treatment modalities on the survival of patients with LRPC using a large patient population provided by the National Cancer DataBase (NCDB). Methods: Patients with LRPC, as defined by the NCCN criteria, between 2004 and 2015 from NCDB were analyzed. Patients are categorized by treatment modalities, including RP, EBRT, PSI, and those who received no local therapy (NLT). Only patients with low Charlson-Deyo comorbidity score, 0 or 1 were included to ensure comparability between treatment groups. A multivariable Cox regression model was developed to determine the adjusted odds of patients' survival. The Kaplan Meier survival plots stratified by treatment were generated to establish the median overall survival (OS). The log-rank test was used to determine significance between treatment groups. Cox regression models were used to produce parameter estimates and hazard ratio (HR) for each age group. Results: A total of 195,452 patients with LRPC were identified from 2004 to 2015. There was a significant practice pattern change with increased utilization of NLT over time, from 11.3% in 2004 to 53.5% in 2015, with a turning point in 2009. The utilization was peaked for RP at 41.6% in 2008, EBRT at 24.3% in 2006, and PSI at 35.3% in 2004, but dropped to 17.6%, 18.1%, and 10.8%, respectively, in 2015. Of different treatment modalities, compared to NLT, RP provided a superior OS with a HR of 0.662, p &lt; .0001; PSI also improved OS with an HR of 0.795, p &lt; .0001. However, EBRT did not improve OS and was potentially detrimental, HR = 1.049, p = 0.01. With age-matched subgroup analysis, the survival advantage based on HR of RP relative to NLT favors RP until the age of 74 but diminishes as age increases. In patients younger than 70, NLT provided comparable survival to EBRT or PSI. The survival advantage of EBRT or PSI is only seen in older patients, at age of 75 or older for EBRT and 70 or older for PSI. Conclusions: There has been a significant treatment pattern change between 2004 and 2015. AS, as represented by the NLT in this study, has become the dominant choice of treatment for LRPC. However, of different treatment modalities, both RP and PSI improve OS. The patients managed with AS had comparable OS to those who received EBRT. The survival benefit of RP is mostly seen in younger patients. Only older patients benefit from PSI or EBRT. This study is limited by its retrospective nature and inherent bias in NCDB.

PO-1817 HDR brachytherapy effectiveness in local relapse prostate cancer: 10-year experience

PO-1817 HDR brachytherapy effectiveness in local relapse prostate cancer: 10-year experience

The retinoblastoma tumor suppressor plays different roles in localized and castration-resistant prostate cancer

The retinoblastoma tumor suppressor plays different roles in localized and castration-resistant prostate cancer

Neoadjuvant Systemic Therapy Prior to Radical Prostatectomy for Clinically Localized High-Risk Prostate Cancer

Radical prostatectomy (RP) remains a standard treatment option for clinically localized high-risk prostate cancer. While RP provides excellent local control, patients with high-risk disease remain at considerable risk for recurrence after surgery. Disease relapse may be the result of occult distant metastases or regional micrometastatic disease at the time of surgery. Accordingly, the role of systemic (neoadjuvant) therapy prior to RP has been investigated. Proposed neoadjuvant regimens: include monotherapy or combinations of chemotherapy, hormonal deprivation, and immunologic agents. Randomized trials using androgen deprivation have demonstrated improved pathologic outcomes, including pathologic downstaging and decreased risk of positive surgical margins, extracapsular extension, and seminal vesical invasion. However, these, albeit early, trials did not reliably demonstrate improved post-prostatectomy oncologic outcomes. More recent trials have evaluated novel combinations of chemo-hormonal therapy and immunologic based therapies. These studies are currently maturing and offer the promise, pending findings, of potentially informing future practice. In this review, we highlight the pathophysiologic basis and contemporary evidence for neoadjuvant therapy prior to RP for clinically localized high-risk prostate cancer.

Uncovering interpretable potential confounders in electronic medical records

Randomized clinical trials (RCT) are the gold standard for informing treatment decisions. Observational studies are often plagued by selection bias, and expert-selected covariates may insufficiently adjust for confounding. We explore how unstructured clinical text can be used to reduce selection bias and improve medical practice. We develop a framework based on natural language processing to uncover interpretable potential confounders from text. We validate our method by comparing the estimated hazard ratio (HR) with and without the confounders against established RCTs. We apply our method to four cohorts built from localized prostate and lung cancer datasets from the Stanford Cancer Institute and show that our method shifts the HR estimate towards the RCT results. The uncovered terms can also be interpreted by oncologists for clinical insights. We present this proof-of-concept study to enable more credible causal inference using observational data, uncover meaningful insights from clinical text, and inform high-stakes medical decisions.

Association between health-care system and prostate cancer mortality for African American men with localized and metastatic prostate cancer.

27 Background: African American (AA) men with prostate cancer (PC) present with more advanced disease and have worse survival than comparable non-Hispanic White (White) men. Recent studies suggest that receiving care within an equal access setting may attenuate these disparities. We hypothesize that AA men receiving care within the Veterans Health Administration (VHA) will have improved outcomes compared to AA men receiving care in the general population as assessed by the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We identified AA men diagnosed with PC between 2004 and 2015 in the VHA and SEER. For comparisons of covariate distributions across subgroups, we used the chi-squared test with continuity correction. We analyzed the cumulative incidence (with 95% confidence intervals (CIs)) of PC specific mortality (PCSM) in the VHA and SEER. Additionally, multivariable Cox proportional hazards models controlling for demographic information were performed. Results: The cohort included 85,409 AA men (VHA: 27,415, SEER: 57,994). Median follow-up was 4.79 years in the VHA and 5.16 years in SEER. In the VHA, AA men were more likely to present with localized disease (VHA 94.7% vs SEER 86.4%, p &lt; 0.001) and less likely to have metastatic disease (3.2% vs 4.3%, p &lt; 0.001). The 5-year cumulative incidence of PCSM was lower for patients in the VHA (VHA: 3.8% [CI: 3.5-4.1%] vs. SEER: 5.0% [CI: 4.8-5.2%], p &lt; 0.001). The PCSM difference was largest in men with metastatic disease. In metastatic patients, cumulative incidence of PCSM at five years was significantly lower in the VHA (VHA 52.5% [CI: 48.0-56.5%] vs. SEER 64.8% [CI: 62.3-67.1%], p &lt; 0.001). In contrast, AA men with localized disease had similar PCSM in the VHA and SEER (VHA 2.4% [CI: 2.2-2.6%] vs. SEER 2.6% [CI: 2.4-2.7%], p = 0.09 at five years). On multivariable analysis, VHA system was associated with lower PCSM [Hazard Ratio (HR): 0.91, p &lt; 0.001]. There was a significant interaction between VHA system and distant metastases at diagnosis [p &lt; 0.001] indicating larger differences in PCSM by healthcare system in metastatic patients as compared to localized patients. VHA system was associated with reduced PCSM in metastatic patients [HR 0.84, p &lt; 0.001] but not in localized patients [HR 0.96, p = 0.13]. Conclusions: AA men in the VHA had a significantly lower incidence of PCSM than those in the SEER database, especially for those who presented with distant metastases at diagnosis. Future work should examine how cost and access to care affect disparities in outcomes for AA men.

Cohort study of oligorecurrent prostate cancer patients: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.

106 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligorecurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions were removed in 356 (94.4%) patients. Within three months from surgery, 25 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 235 patients experienced BCR and 129 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 11.1 months and 10.5 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.9) and 34.9 (24.7-43.5) months. At two years of follow-up, BFS rate was 31.9% and TFS rate was 56.6%. In multivariable analyses, higher preoperative PSA (HR: 1.06), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.7), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligorecurrent PCa.

Oncologic Impact and Safety of Pre-Operative Radiotherapy in Localized Prostate and Bladder Cancer: A Comprehensive Review from the Cancerology Committee of the Association Française d'Urologie.

Simple SummaryRadiotherapy may have an interesting role of reinforcing the loco-regional control of cancer, in addition to surgery, when used as a preoperative treatment. This sequence has demonstrated its efficacy and safety in various malignancies, but no strong data exist in the era of uro-oncology. In this review article, we aim to highlight the potential usefulness of preoperative radiotherapy in prostate and muscle-invasive bladder cancer, aiming to enhance pathological response and local control and to prevent intraoperative tumor seeding. We also emphasize the need for further clinical studies assessing the functional safety of subsequent surgical procedures in a competitive context of new systemic agents that have proven to demonstrate a survival benefit in locally advanced urologic cancers.Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.

Prostate Cancer

Prostate cancer is the most commonly diagnosed noncutaneous malignancy in men in the United States. This chapter discusses the epidemiology, pathogenesis, and diagnosis of prostate cancer, as well as risk factors, the use of digital rectal examination and prostate-specific antigen measurement for screening, and staging for the disease. Also reviewed are the natural history of untreated prostate cancer; the treatment of localized and advanced prostate cancer, including prostatectomy, radiation therapy, and androgen deprivation therapy; and the prevention of prostate cancer. Figures illustrate the incidence rates of prostate cancer by race, age-adjusted and/or age-specific cancer of the prostate, the risk of a diagnosis in 20 years (based on being cancer free at certain ages), the 5-year survival rate, and the overall survival in patients with early prostate cancer treated with observation or radical prostatectomy. Tables in this chapter review the clinical staging definitions and the combined-modality staging approach to prostate cancer. This chapter contains 6 figures, 8 tables and 104 references Keywords: Prostate cancer, digital rectal exam, PSA, prostatectomy, men's health, prostate cancer screening

1304Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the EPIC study

Abstract Background Metabolomics studies in cancer epidemiology have mostly focused on single metabolite-cancer site associations. Pan-cancer analyses may have larger statistical power when identifying metabolites showing consistent associations across cancer sites, while allowing the identification of site-specific associations. Methods Data from seven cancer-specific case-control studies nested within the European Prospective Investigation into Cancer and Nutrition Cohort (EPIC) were pooled, resulting in a total sample of 7,957 case-control pairs from eight cancer types (breast, colorectal, endometrial, gallbladder, kidney, localized prostate and advanced prostate cancer, and hepatocellular carcinoma). A total of 117 pre-diagnostic blood metabolites were measured. After clustering the most highly correlated ones together, we studied the association between 50 features (metabolites or clusters of metabolites) and cancer risk in multivariate penalized conditional logistic regression models controlled for body mass index using the data shared lasso. Results We identified: (i) 8 features with consistent associations across cancer sites: e.g., glutamine and C4-acylcarnitine, one cluster of lysophosphatidylcholines and one of phosphatidylcholines were inversely associated with cancer, while C10-acylcarnitine, valine and proline showed positive associations; (ii) 11 features with heterogeneous associations across cancer sites: e.g., arginine was positively associated with colorectal cancer only, while one cluster of sphingomyelins was associated inversely with hepatocellular carcinoma and positively with endometrial cancer. Conclusions Our pan-cancer analysis notably identified metabolites showing consistent associations with cancer risk across different cancer-types. Key messages Our results could lead to the identification of common pathways shared across different cancer types.

Comparison of EBRT and I-125 seed brachytherapy concerning outcome in intermediate-risk prostate cancer

PurposeThis study’s objective was the comparison of external beam radiotherapy (EBRT) and I‑125 seed brachytherapy regarding clinical outcome and development of side effects.Patients and methodsIn all, 462 localized intermediate-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seed brachytherapy or EBRT with a dose of 74 or 78 Gy were included: 297 patients were treated with EBRT and 165 with seeds. Biochemical no evidence of disease (bNED) rates according to Phoenix definition as well as late gastrointestinal and urogenital side effects (EORTC/RTOG) were assessed.ResultsPatients were followed up yearly with a median follow-up of 54 (3–192) months. Observed bNED rates for 74 Gy, 78 Gy and seeds were 87, 92, and 88% after 5 years and 71, 85, and 76% after 9 years, respectively. No significant differences were found comparing seeds with 74 Gy (p = 0.81) and 78 Gy (p = 0.19), as well as between 74 and 78 Gy (p = 0.32). Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥ 2 toxicity compared to seeds, but at no point of the follow-up more than 10% of all patients. However, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 33% RTOG grade ≥ 2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time.ConclusionFavorable intermediate-risk prostate cancer patients can be treated either by external beam radiotherapy (74/78 Gy) or permanent interstitial seed brachytherapy.