bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy lifestyle, Agent Orange exposure, and inherited PCa risk: An analysis of the Million Veteran Program.
Authors: Pagadala Meghana , Lui Asona , Lynch Julie Ann , Karunamuni Roshan , Lee Kyung Min , Plym Anna , Rose Brent S. , Carter Hannah , Kibel Adam S. , DuVall Scott L. , Gaziano J. Michael , Panizzon Matthew , Hauger Richard , Seibert Tyler M
Published: March 2023

210

Background: Prostate cancer (PCa) risk is understood to be mostly unmodifiable and inherited, but there is evidence that environmental and behavioral factors may also contribute. A recent study of health professional cohorts suggests a healthy lifestyle can mitigate a high inherited risk of lethal PCa. It is unknown how modifiable factors affect PCa risk in more diverse populations. Our objective was to determine the effects of healthy lifestyle and Agent Orange exposure on PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population. Methods: The Million Veteran Program (MVP) is a national, population-based cohort study of United States military veterans conducted 2011-2021 with 590,750 male participants available for analysis. Healthy lifestyle was quantified as: A healthy lifestyle score (range 0-3) was calculated with a point assigned for each of the following at MVP enrollment: not a current smoker, body mass index (BMI) 30 and strenuous activity 2 days per week. Agent Orange exposure was obtained from VA records. Genetic risk was assessed via a polygenic hazard score using genotype data. Results: Healthy lifestyle was independently associated with reduced metastatic PCa (HR 0.82, 95% CI 0.77–0.87, p<0.001) and fatal PCa (HR 0.76, 95% CI 0.68–0.86, p<0.01) when accounting for family history, genetic risk, and race/ethnicity. The benefit of healthy lifestyle was also observed in Black participants on subset analysis. Agent Orange exposure was an independent factor for PCa diagnosis (HR 1.06, 95% CI 1.04-1.09). Conclusions: Adherence to a healthy lifestyle is associated with reduced risk of metastatic or fatal PCa, which offsets inherited risk.
Nivolumab plus ipilimumab for the treatment of post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC): Additional results from the randomized phase 2 CheckMate 650 trial.
Authors: Sharma Padmanee , Krainer Michael , Saad Fred , Castellano Daniel , Bedke Jens , Kwiatkowski Mariusz , Patnaik Akash , Procopio Giuseppe , Wiechno Pawel , Kochuparambil Samith Thomas , Thomas Christian , Arranz Arija Jose Angel , McCune Steven L. , Hansen Steinbjorn , Daugaard Gedske , Amin Neha P. , Wang Yumeng , David Justin M. , Pachynski Russell Kent
Published: March 2023

22

Background: In preliminary analyses from the randomized phase 2, open-label CheckMate 650 trial, nivolumab (NIVO) 1 mg/kg (N1) plus ipilimumab (IPI) 3 mg/kg (I3) Q3W × 4 doses showed clinical activity in patients (pts) with post-chemotherapy (post-CT) mCRPC, particularly those with high tumor mutational burden (TMB), but early toxicity contributed to treatment discontinuations. Here, we report results from pts with post-CT mCRPC receiving alternative NIVO+IPI dosing regimens vs IPI alone vs cabazitaxel (CABA) in CheckMate 650. Methods: Newly enrolled pts previously treated with docetaxel for mCRPC were randomized 2:2:1:2 to cohorts D1 (NIVO 3 mg/kg [N3] + IPI 1 mg/kg [I1] Q3W × 4 doses then NIVO 480 mg Q4W), D2 (N1 Q3W × 8 doses + I3 Q6W × 4 doses then NIVO 480 mg Q4W), D3 (I3 Q3W × 4 doses), or D4 (CABA 20 or 25 mg/m2 Q3W + prednisone 10 mg × 10 doses). Crossover from cohorts D3 and D4 to cohort D1 was allowed after radiographic progressive disease. Outcomes included safety, objective response rate (ORR), prostate-specific antigen response rate (PSA-RR; confirmed PSA decline ≥ 50% from baseline), radiographic progression-free survival (rPFS) per blinded independent central review (BICR), and overall survival (OS). Associations between efficacy and TMB were assessed. Results: Overall, 259 pts were randomized (D1, n = 73; D2, n = 74; D3, n = 38; D4, n = 74). Median (range) follow-up for OS was 23.3 (6.0–31.5) months. In the NIVO+IPI cohorts (D1 and D2), median duration of therapy was 2.8 and 2.4 months; the median number of IPI doses received was 4 and 2, and 15% and 26% of pts discontinued due to study drug toxicity, respectively. Two pts died due to study drug toxicity (1 each in cohorts D1 and D2). Key safety and efficacy data are shown. Several pts in cohorts D1 and D2 showed notable reductions (75-100%) in tumor size and PSA. Approximately one-third of pts in cohorts D3 and D4 crossed over to D1. Based on preliminary analyses in small numbers of evaluable pts, there was no clear and consistent association between efficacy and tissue or blood TMB in the NIVO+IPI cohorts (D1 and D2). Conclusions: These results further support the clinical activity of NIVO+IPI in select pts with post-CT mCRPC. Detailed evaluations of the characteristics of responders to NIVO+IPI, including more expansive biomarker analyses, are warranted. Clinical trial information: NCT02985957 . [Table: see text]
A comparative analysis of patients presenting with optic canal metastasis of prostate cancer.
Authors: Kelkar Neil , Wang Jue
Published: March 2023

23

Background: Prostate cancer (PCa) is the second-most diagnosed cancer and the second leading cause of cancer deaths in United States Males. Due to an emphasis on early detection of PCa, only a small percentage present with distant disease. We report cases of ocular metastasis of PCa, a late finding of PCa. Methods: Systematic review of the literature and pooled analysis of published cases of PCa with optic canal or orbital metastasis, including one from our institution. A subgroup analysis compared those who presented with optic metastases as their initial presentation (IP) versus those who presented with optic metastases after diagnosis (AD). Results: 39 patients with ocular metastasis of PCa were selected for this study. Twenty-one cases (53%) presented with ocular metastasis in the initial presentation, and 18 presented with an optic canal metastasis after diagnosis. The overall average age was 66 years (45-85 years). The average age for the IP group was 70 years (59-85 years) and 62 years (45-70 years) for the AD group. Metastatic sites varied between cases. Nineteen cases (49%) presented with widespread lesions involving the axial skeleton, with 8 IP cases (44%) versus 11 AD cases (52%). Ten cases (26%) involved solitary metastases to the optic nerve, optic disc, choroid, or orbit, with 5 IP cases (2%) versus 5 AD cases (24%). Three cases (7.5%) presented with bilateral orbital metastases. One case (2.5%) involved bilateral solitary lesions to the optic nerves. The common complaints patients presented with were proptosis (33%), diplopia (26%), decreased visual acuity (41%), and vision loss (10.3%). Thirty-seven cases reported primary adenocarcinoma on histology (95%). Thirty cases reported mortality data, with 16 reporting patient death after diagnosis. Of these, 6 cases (out of 12) report death from PCa in the IP group, and 10 cases (out of 18) report death from PCa in the AD group. Conclusions: Despite early prostate cancer screening increases, patients can present with distant metastasis as their initial presentation. We recommend prompt tumor molecular/genetic testing to inform targeted treatment when faced with atypical cases.
Disparities in prostate cancer diagnoses in persons experiencing homelessness.
Authors: Mayo Zachary S , Parker Sean M. , Kilic Sarah S , Weleff Jeremy , Strzalka Colleen , Phelan Michael P. , Mian Omar Y. , Stephans Kevin L. , Suh John H. , Tendulkar Rahul D.
Published: March 2023

24

Background: We previously reported that persons experiencing homelessness (PEH) are significantly less likely to undergo prostate specific antigen (PSA) testing compared to persons not experiencing homelessness (non-PEH). The purpose of this study was to determine if reduced PSA testing in PEH results in more advanced prostate cancer diagnoses. Methods: We identified PSA screening eligible PEH (men ages 50-69) from an institutional registry of all patients that presented to our healthcare system as homeless from 2014 to 2021. A matched cohort of non-PEH was generated for comparison. Institutional CPT and HCPCS billing codes for PSA testing were available beginning 01/01/2017 and cross-referenced to identify PEH and non-PEH who underwent PSA testing at least once between 01/01/2017 and 12/31/2021. In patients with ≥ 1 PSA test, we recorded screening, oncologic and treatment related variables. Patients with a history of prostate cancer diagnosed outside the study timeframe were excluded. Results: A total of 9,249 PEH were identified, with 1,597 meeting PSA screening criteria during the study timeframe; 3,370 screening eligible non-PEH were available for comparison. The median age was 59.0 for PEH and 60.0 for non-PEH. PEH were significantly less likely to have a primary care provider (58% vs 81%, p<0.001) or to have a PSA test (12% vs 33%, p<0.001). Among patients with a PSA test, PEH were significantly less likely to have multiple PSA tests compared to non-PEH (28% vs 61%, p<0.001) and significantly more likely to have a PSA ≥ 4.0 (18% vs 12%, p=0.028). In patients with a PSA ≥ 4.0, PEH were less likely to receive a prostate biopsy (37% vs 61%, p =0.009) and there was a trend towards decreased prostate MRI (11% vs 25%, p=0.085). A total of 6 PEH (0.4%) and 46 non-PEH (1.4%) were diagnosed with prostate cancer. The median PSA at diagnosis was 12.6 in PEH vs 7.0 in non-PEH (p=0.052). PEH were significantly more likely to present with high/very high risk disease (4/6 [66%] vs 9/46 [20%], p=0.019); no PEH had very low/low risk disease compared with 20 (43.5%) non-PEH. PEH were more likely to present with lymph node positive or metastatic disease (3/6 [50%] vs 3/46 [7%], p=0.016). The median time from biopsy to treatment was 119 days in PEH and 76 days in non-PEH (p=0.391). Conclusions: PEH are less likely to receive prostate cancer testing following an elevated PSA and more likely to present with high risk advanced prostate cancer. Interventions to increase prostate cancer awareness in PEH are needed to reduce disparities.
Racial differences in survival and healthcare resource utilization among Medicaid-insured adults with metastatic castration-sensitive prostate cancer.
Authors: DerSarkissian Maral , Gupta Deepshekhar , Ivanova Jasmina , Niyazov Alexander , Zanardo Enrico , Guo Tracy , Wang Jingru , Duh Mei Sheng , Freedland Stephen J.
Published: March 2023

26

Background: Racial inequalities in healthcare have long existed in the United States, with Black or African American (BAA) men having higher overall cancer death rates compared to other racial or ethnic groups. One of the greatest disparities is in prostate cancer (PC), which disproportionately affects BAA men, though when matched for stage, whether outcomes differ by race is controversial. This study assessed differences in overall survival (OS) and healthcare resource utilization (HRU) by race in Medicaid-insured patients with metastatic castration-sensitive prostate cancer (mCSPC). Methods: This retrospective longitudinal cohort study evaluated de-identified administrative claims data from the Centers for Medicare and Medicaid Services 100% Medicaid data files, from 01/01/2010 - 12/31/2018. The study included adult patients with a diagnosis for PC, ≥1 claim for androgen deprivation therapy (ADT), diagnosis of metastasis before or within 90 days after ADT, and continuous eligibility for ≥6 months pre-index (defined baseline period) and ≥3 months post-index. The date of first receipt of ADT or first receipt of novel hormonal therapy or docetaxel if initiated within 30 days before ADT defined the index date. OS and HRU were assessed from the index date to the earliest of end of continuous eligibility, data availability, or death. A multivariable Cox proportional hazards model of OS and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index (CCI), baseline HRU, and clinical characteristics. Results: The study included 1,488 patients with mCSPC (467 [31%] BAA, 446 [30%] White [W], 219 [15%] Hispanic [H], 356 [24%] Other races [O]). H were the oldest (mean age 68 years), followed by O (67 years), W (64 years), and BAA (63 years). BAA and H had the highest CCI (0.6), followed by O (0.5), and W (0.4). Median unadjusted OS was 71.3 months in H, 57.1 months in O, 52.1 months in BAA, and 44.9 months in W. After adjustment, H had significantly lower risk of death compared to W (hazard ratio [95% confidence interval (CI)]: 0.65 [0.43, 0.96]) and BAA patients had comparable survival to W (0.91 [0.69, 1.22]). Adjusted incidence rate ratios (IRR) showed significantly lower incidence of PC-related outpatient (OP) visits for BAA as compared to W (IRR [95% CI]: 0.71 [0.55, 0.99]), per patient per year. The remaining HRU endpoints were not significantly different among racial groups. Conclusions: Among Medicaid-insured adult patients with mCSPC, H were more likely to live longer than W patients. BAA patients had similar survival and lower rates of PC-related OP visits as compared with W, which shows differential use of PC-related healthcare resources between BAA and W.
Gender disparities in the National Institutes of Health funding for genitourinary oncology.
Authors: Farooq Muhammad Zain , Khan Sara , Zahid Ibrahim , Sohail Aruba , Jaglal Michael Vishal
Published: March 2023

264

Background: Traditionally, women are under-represented in academic fields and thus less likely to receive grants and funds. Here we assessed the National Institutes of Health (NIH) funding trend in allocation of R401 grants in Genito-urinary oncology (GU) stratified by gender. Methods: The data were retrieved from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditure) using GU-related search terms from 2018-2021. The gender was categorized using Genderize. The number of citations, publications, H-index, and seniority were obtained from Scopus and Web of Science in September 2022. Consumer Price Index was used to adjust funding amount to 2021 equivalent U.S. dollars. Linear regression was used for analysis. Results: A total of 873 NIH-funded R01 grants amounting to $388.5 million were awarded for GU research. Women (n= 206; 23.6% [95% CI: 20.8%-26.4%]) received fewer grants than men (n= 667; 76.4% [95% CI: 73.6%-79.2%]). Trending from 2018 to 2021, there was no significant difference in the number of grants awarded among both men (173 to 181, p=0.78) and women (50 to 53, p=0.92) within their groups. Similarly, there was no significant change in the grant amount (in millions) awarded among men (74.2 to 78.7, p=0.47) and women (23.6 to 22.4, p=0.30). Prostate cancer accounted for the greatest proportion of grants (n=689; 78.9% [95% CI: 76.2%-81.6%]), amounting to 304.4 million in 4 years. Of the 269 co-Principal Investigator (PIs), 240 (89.2% [95% CI: 85.5%-92.9%]) were men and 29 (10.8% [95% CI: 7.1%-14.5%]) were women. Male PIs compared to female PIs had a higher no. of publications (135 vs 106, p<0.01). Funding amount was significantly associated with the number of publications (β=0.05; p<0.01), seniority (β=0.10; p=0.015), institution (p<0.01) and degrees (p=0.03). However, there was no significant association with gender (β=0.05; p=0.17). Conclusions: Our analysis shows continued gender disparity in R01 awards as only 1 in 5 grants were awarded to women during the fiscal years of 2018-2021. Thus, concerted efforts are required to bridge this gap and promote gender equity. [Table: see text]
Perioperative outcomes of radical prostatectomy for advanced stage, node positive, and metastatic prostate cancer.
Authors: Simhal Rishabh Kumar , Wang Kerith Ruoyao , Shah Yash , Mark James Ryan , Shah Mihir S , Gomella Leonard G. , Lallas Costas D. , Chandrasekar Thenappan
Published: March 2023

270

Background: Historically, surgical management with radical prostatectomy (RP) has been a definitive treatment option only for localized prostate cancer (PCa). However, recent studies suggest an overall survival benefit to treating the primary tumor with radiation therapy in metastatic PCa (mPCa). Therefore, RP may have a role in treating mPCa, but the perioperative safety of that remains unclear. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the National Surgical Quality Improvement Project (NSQIP) database. Methods: RPs performed between 2019-2020 were identified in NSQIP and the corresponding Prostatectomy-Targeted Participant Use File. Cases were grouped into six distinct categories: T1N0M0-T2N0M0; T3N0M0; T4N0M0; T1-3N1M0; T4N1M0; and T1-4N0-1M1. Baseline age, race, and medical comorbidities were compared between the groups. Patients were then further grouped into T1-2N0M0 versus T3-4N0M0 cases to compare the effect of locally advanced disease, TanyN1M0 versus TanyN0M0 to compare the effect of node-positivity, and TanyN0M1 versus TanyN0M0 to compare the effect of metastases. 30-day outcomes, operative time, hospital length-of-stay, 30-day mortality, readmissions, reoperations, major complications, minor complications, and surgery-specific complications were compared between groups. Results: Pathologic staging was available for 5,248 RPs. Baseline demographics were largely similar, with the exceptions of increased Black race, diabetes, and smoking in the node-positive-group and increased age in the T4 group. There was a slightly higher rate of minor complications in the locally advanced (T3-4N0M0) versus localized (T1-2N0M0) group, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. In comparison to node-negative patients (T1-4N0M0), node-positivity (T1-4N1M0) was associated with longer operative time, LOS, and incidence of 30-day renal failure, but was otherwise not associated with a higher rate of any complication. Compared to non-metastatic cases (T1-4N0M0), metastatic cases (T1-4N0M1) were associated with a higher rate of bleeding, prolonged-NG-tube use, ureteral obstruction, and LOS. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe; it is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localized prostate cancer. Given the potential survival benefit in treating the primary tumor in advanced disease, there may be a role for RP in treating patients with advanced PCa.
Associations between patient sociodemographic factors and non-treatment for localized prostate cancer.
Authors: Novosel Madison , Smani Shayan , Marks Victoria A. , Jeong Farah , Sprenkle Preston , Leapman Michael
Published: March 2023

307

Background: 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 616,479 patients diagnosed with localized prostate (cT1-4N0M0) cancer from 2010 to 2017 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. 29.0% were diagnosed with low, 43.7% with intermediate, and 28.4% with high-risk prostate cancer. There were 71,848 (11.7%) who did not undergo initial treatment, including 46,269 (64.4%) with low, 18,376 (25.6%) with intermediate, and 7,203 (10.0%) with high-risk disease. Overall, non-treatment increased for low-risk (11.6% versus 47.0%), intermediate (4.4% versus 9.7%) and high risk (3.4% versus 4.7%). Compared with White patients, Black patients had lower odds of definitive treatment. This effect was more pronounced for patients with high (OR 0.63, 95% CI 0.59-0.67) than intermediate (OR 0.78, 95% CI 0.75-0.82) risk disease. Asian patients had lower odds of treatment compared with White patients across all disease risk strata (OR 0.82, 95% CI 0.77-0.87). There were lower odds of treatment among American Native/Alaskan Native versus White patients with high-risk prostate cancer (OR 0.58, 95% CI 0.39-0.85). Uninsured (OR 0.41, 95% CI 0.39-0.44, p<0.001), and Medicaid-insured (OR 0.69, 95% CI 0.65-0.72, p<0.001) patients were significantly less likely to be treated overall. The effects of Black race and non-treatment did not differ by insurance status (p-value for interaction=0.237). Conclusions: Patient race and insurance are significantly associated with non-treatment for aggressive prostate cancer.
Increased prostate volume on transrectal ultrasound and magnetic resonance imaging are potential risk factors for acute urinary retention following transperineal prostate biopsy.
Authors: Sandberg Maxwell , Whitman Wyatt , Hingu Janmejay , Thakker Parth , Rong Anita , Bercu Caleb , Greenberg Jacob W. , Davis Ronald , Hemal Ashok , Tsivian Matvey
Published: March 2023

308

Background: Prostate biopsy is one of the most frequently performed procedures in urology. Recently, there has been a nationwide shift towards offering transperineal (TP) biopsies due to a reduced rate of infectious complications compared to the transrectal (TR) route. While infection may be reduced, TP biopsy is not without complication, most notably, acute urinary retention (AUR). Estimates vary as to the true rate of AUR following TP biopsy. Further, some studies have reported higher rates of AUR following TP biopsy than TR. Here we report the rate of AUR following TP biopsy at a single academic institute and relate it to risk factors for developing AUR. Methods: Retrospective case-control study. All biopsies performed with TR ultrasound (TRUS) guidance using TP technique under general anesthesia in dorsal lithotomy with a grid template. TRUS volumes were recorded during the procedure, and MRI volumes were calculated by a trained radiologist pre-biopsy. Charts of men undergoing TP biopsy from 2012 to present were reviewed. AUR was defined as patients who reported inability to urinate within 72 hours post-biopsy and underwent thorough evaluation including PVR and relevant H&P and required catheter placement. Independent samples t-test was run to relate AUR to risk factors pre/post-biopsy. Results: A total of 767 TP biopsies were completed in the study window, but not all had TRUS/MRI data. Total rate of AUR was 5.48% (N=42/767). Risk factors for AUR were increased TRUS (p=0.009, [6.49, 42.30]) and MRI prostate volumes (p=0.027, [2.90, 43.13]). Age, number of cores taken, and number of previous biopsies were not associated with AUR. Conclusions: While data is scant, the rate of AUR at our institution is consistent with current estimates in the literature. There is a growing body of evidence that the rate of AUR post-TP biopsy is higher than TR, but more investigation is needed. There is also a gap in the literature on risk factors predicting AUR after TP biopsy, however our findings are relatively consistent with the few studies currently published. Urologists must recognize patients presenting for TP biopsy with large volume prostates and consider altering management to prevent AUR. [Table: see text]
Influence of molecular imaging on patient selection for treatment intensification prior to salvage radiation therapy for prostate cancer: A post hoc analysis of the PROPS trial.
Authors: Tremblay Samuel , Alhogbani Mofarej , Weickhardt Andrew , Davis Ian D. , Scott Andrew Mark , Hicks Rodney J. , Metser Ur , Chua Sue , Davda Reena , Punwani Shonit , Payne Heather Ann , Tunariu Nina , Ho Bao , Young Sympascho , Bauman Glenn , Emmett Louise , Pouliot Frederic
Published: March 2023

316

Background: The impact of molecular imaging (MI) on patient management after biochemical recurrence (BCR) following radical prostatectomy has been described in many studies. However, it is not known if MI-induced management changes are appropriate. This study aimed to determine if androgen deprivation therapy (ADT) management plan is improved by MI in patients who are candidates for salvage radiation therapy. Methods: Data were analyzed from the multicenter prospective PROPS trial evaluating PSMA/Choline PET in patients being considered for salvage radiotherapy (sRT) with BCR after prostatectomy. We compared the pre- and post-MI ADT management plans for each patient and cancer outcomes as predicted by the MSKCC nomogram. A higher percentage of predicted BCR associated with ADT treatment intensification after MI was considered as an improvement in a patient’s management. Results: Seventy-three patients with a median PSA of 0.38 ng/mL were included. In bivariate analysis, a positive finding on MI (local or metastatic) was associated with decision to use ADT with an odds ratio of 3.67 (95% CI, 1.25 to 10.71; p=0.02). No factor included in the nomogram was associated with decision to use ADT. Also, MI improved selection of patients to receive ADT based on predicted BCR after sRT: the predicted nomogram 5-year biochemical-free survivals were 52.5 % and 43.3%, (mean difference, 9.2%; 95% CI 0.8 to 17.6; p=0.03) for sRT alone and ADT±sRT subgroups, while there was no statistically significant difference between subgroups before MI. Conclusions: PSMA and/or Choline PET/CT before sRT can potentially improve patient ADT management by directing clinicians towards more appropriate intensification.
Development and validation of a novel radiomic model for predicting post-treatment prostate cancer recurrence.
Authors: Huynh Linda My , Taylor Olivia , Wang Shuo , Baine Michael
Published: March 2023

317

Background: Multiparametric magnetic resonance imaging (mpMRI)-derived radiomic features have been shown to capture sub-visual patterns for quantitative characterization of tumor phenotypes in prostate cancer (PC) patients. The present study seeks to develop, test, and validate a mpMRI-derived radiomic model for predicting PC recurrence following initial treatment. Methods: mpMRI was obtained from 76 patients who had undergone radical prostatectomy for treatment of localized PC. All patients had >2 years follow-up with monitoring via prostate specific antigen (PSA). Patients with neo-adjuvant/adjuvant treatment were excluded. Regions of interest were manually delineated on each mpMRI and radiomics features were extracted. Stability on histogram matching was assessed via interclass correlation coefficients (ICC) and a pre-established feature selection pipeline excluded redundant features. The most important and non-redundant features were then aggregated into a radiomic model against a primary outcome of PC recurrence. Patients were randomly split 3 to 1 to training and validation datasets and the training dataset was used to iteratively train and test the best parameters for a Random Forest predictive model. The model with the best parameters as determined by receiver-operator curve (ROC) analysis was then applied to the validation set. ROC analysis was conducted and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were reported. Results: Clinicodemographic of the 76 patients included in analysis are displayed in Table. 924 radiomic features were initially extracted and 75 (8.1%) features were determined to be stable and robust following histogram matching. Based on the figure selection pipeline, six features were determined to be important and non-redundant. These features were iteratively tested in the training dataset (n=56) and the model with the best parameters yielded a mean ROC with area under the curve (AUC) of 0.95 ± 0.06. After application to validation dataset (n=20), the model yielded an AUC of 0.67. Sensitivity, specificity, PPV, and NPV were 33%, 100%, 40% and 100%, respectively. Conclusions: Radiomic analysis of 76 PC patients yielded six mpMRI-derived radiomic features significantly correlated with PC recurrence following primary treatment. When aggregated and applied to a validation dataset, the final radiomic model yielded 100% specificity in predicting PC recurrence. These findings represent excellent potential for the development of a radiomic-based diagnostic tool with high positive predictive value in identifying patients at high-risk for PC recurrence at time of initial PC diagnosis. Future projects will seek to incorporate patient demographics and disease characteristics to further improve model sensitivity and validation of this model will be pursued with an external cohort of patients.[Table: see text]
Association between sociodemographic factors and diagnosis of advanced prostate cancer in early life.
Authors: Smani Shayan , Novosel Madison , Jeong Farah , Marks Victoria A. , Sprenkle Preston , Leapman Michael
Published: March 2023

32

Background: A subset of patients are diagnosed with lethal prostate cancer early in life, before PSA screening is typically initiated. To identify opportunities for improved detection we evaluated patient clinical and sociodemographic factors associated with advanced versus localized prostate cancer diagnosis across the age spectrum. Methods: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with prostate cancer in 2004-2016. We compared characteristics of patients diagnosed at advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as <55 (before screening is usually initiated), 55-65, 65-75, and >75 years. Results: We identified668,486 patients who met inclusion criteria (mean age at diagnosis=64.6 years), including 33,455 (5.0%) with advanced disease at diagnosis. Uninsured (odds ratio, OR=3.78, 95% confidence interval, CI 3.56-4.02) and Medicaid-insured (OR 2.84, 95% CI 2.70-3.00) versus commercially insured patients were more likely to be diagnosed with advanced disease, however this effect was more pronounced for younger patients. Among patients <55 years, uninsured (OR 4.63, 95% CI 4.08-5.25) and Medicaid (OR 3.59, 95% CI 3.22-3.99) versus commercial insurance were associated with greater odds of advanced cancer at diagnosis. Similarly, residence in the lowest versus highest income quintile (OR 1.21, 95% CI 1.04-1.40) was associated with increased odds of advanced prostate cancer in patients <55 years. Black versus White race was associated with increased odds of advanced prostate cancer at diagnosis later in life (OR 1.15, 95% CI 1.11-1.19), however race was not significantly associated with stage of prostate cancer in those <55 years (p=0.29). Conclusions: Sociodemographic disparities in advanced stages of prostate cancer diagnosis were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early prostate cancer screening by health insurance.
Analysis of false-positive biopsy results of PIRADS 4 lesions in multiparametric magnetic resonance imaging of the prostate: Experience from a single nonacademic center using cognitive fusion.
Authors: Mota Augusto C. A. , de Souza Bianca Carla Azevedo , Novaes Marco Antonio Soares , do Amaral Maria Estela Pompeu , de Souza Maiara Ferreira , Athanazio Daniel Abensur
Published: March 2023

321

Background: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has been increasingly used in the algorithm of the initial diagnosis of patients suspected to harbor prostate cancer (PCa) with the aim of improving the selection of patients who really need a biopsy. Yet patients with PI-RADS 5 lesions almost always have cancer found in their prostates, the same is not true for patients with PI-RADS 4. In this study we sought to describe pathological findings in target biopsies of PI-RADS4, and to identify clinical data that could predict those patients with benign findings. Methods: A retrospective study was conducted in a data bank collected prospectively from December 2015 through April 2022 in a single nonacademic center. The whole series consist of 547 patients, all of whom had a mpMRI of the prostate (reports as per PI-RADS version 2) followed by cognitive fusion prostate biopsy performed by a single, experienced radiologist. All biopsy specimens were read by a specialist in urological pathology. Out of these, 259 had PI-RADS 4 lesion, and 83 had PI-RADS 5. Results: We found a false positive rate of 29% and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Different histologic patterns were observed among target biopsies. At multivariate analysis, PIRADS lesion ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The 76 cases showed normal histology (n = 22), a combination of chronic inflammation, reactive epithelium, and glandular atrophy (n = 18), glandular atrophy (n = 9), stromal proliferation consistent with nodular hyperplasia (n =7), a combination of chronic inflammation, reactive epithelium and glandular atrophy (n = 6), chronic inflammation (n = 4) and HGPIN (n = 10). The small number (n=3) of false PI-RADS5 lesions precluded further analyses. Conclusions: Benign findings are common in PI-RADS4 lesions and most of them did not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict higher probability of false positive results in patients with PI-RADS 4 lesions.[Table: see text]
De novo prostate cancer in renal transplant recipients: A single-center study.
Authors: Sridhar Arthi , Yohannan Binoy , Kaur Harmanpreet , Maithel Neha
Published: March 2023

326

Background: Renal transplant recipients (RTRs) are at an increased risk of developing solid organ malignancies. Given improved allograft survival and life expectancy, the incidence of prostate cancer (PC) in RTRs appears to be increasing. Previous studies have reported the incidence of PC among RTRs to be between 0.3% and 3.24%. Limited data is available on the clinical characteristics, treatment, predictive markers, and outcomes of PC in RTRs. Methods: We performed a single-center retrospective study of male RTRs who developed PC. We collected the following data on RTRs who underwent transplantation between January 1, 1999, and December 31, 2019: baseline demographics, cause of end-stage renal disease (ESRD), duration of dialysis prior to RT, type of RT (cadaveric vs. living donor), immunosuppressive regimen, interval from RT to diagnosis of PC, stage of PC, type of treatment received, allograft survival, and overall survival (OS) were collected. Results: Among 1093 male RTRs, 15 (1.37%) developed PC. The median age at diagnosis of PC was 60 (range, 49-75) years. Subject races were African American (n=7), Hispanic (n=3), White (n=3), and other (n=2). The median duration from transplant to diagnosis of PC was 72 (range, 12-156) months. PC was diagnosed at stage I in 13 patients, stage II in 1 patient, and stage IV in 1 patient. The management of these patients consisted of local radiation (LR) alone in 6 patients, LR with leuprolide therapy in 6 patients, and radical prostatectomy alone in 1 patient. The patient with stage IV PC was treated with leuprolide and abiraterone acetate and remains progression free at follow-up of 41 months. The 5-year OS for this cohort of patients was 73.3%. Allograft function was preserved in 13 patients 12 months after diagnosis of PC. No PC-related mortality was noted. Conclusions: The incidence of PC in our analysis appears to be consistent with prior published studies. Most of our RTRs with PC had early-stage disease with excellent 5-year survival. The current standard-of-care treatment modalities for PC appear to be effective in the management of these patients. Allograft function was preserved in the majority of RTRs with PC in this study. Further research is required to evaluate the predictive factors for developing PC in RTR.
Patient opinions on controversies: In regard to low-risk prostate cancer, is Gleason 6 the old Gleason 5?
Authors: Wolinsky Howard , Schraidt James , Lichty Mark , Segal Philip , Berlin Alejandro , Siddiqui Mohummad Minhaj , Washington Samuel L. , Geller Herbert M.
Published: March 2023

329

Background: In 2005, the International Society of Urologic Pathology effectively eliminated Gleason patterns 1 and 2, thus removing Gleason grades 2-5 as a cancer diagnosis. Today, patients with low-risk Gleason 6 prostate cancer, prostate cancer clinicians, guideline writers, and policymakers are facing issues about whether Gleason 6 lesions should be reclassified as noncancer. Some of the issues being discussed among urologists, radiation oncologists, and pathologists focus on whether to reclassify low-risk Gleason 6 prostate lesions as a noncancer with the goal of reducing patient anxiety and financial toxicity. We also asked about biopsy methods, which affects both the low-risk and favorable intermediate-risk populations, that have been a major topic in support organizations over the past two years. We conducted this survey of patients on active surveillance to determine where patients stand on these issues to help guide clinicians, policymakers, and guideline writers. Methods: We conducted a survey in October 2022 asking patients their views on these issues. We invited patients on active surveillance or previously on active surveillance for low-risk prostate cancer to respond to a 40-question survey to share their views on a range of topics related to the diagnosis of Gleason grade 6 lesions as cancer, as well as complementary issues related to innovations in biopsy and active surveillance. We had access to email lists containing ~2,500 names from the AnCan Foundation’s Active Surveillance Virtual Support Group, Active Surveillance Patients International, Prostate Cancer Support Canada, and The Active Surveillor newsletter. Other major prostate cancer support groups also distributed links to the questionnaire posted on SurveyMonkey. Results: At the deadline for placeholders for abstracts, the survey is underway. Questions for patients include: Have you experienced distress (anxiety or depression) because of the cancer label from Gleason 6? Have you experienced financial toxicity, including cancellation of insurance policies or an increase in rates, because of the cancer diagnosis? If Gleason 6 was reclassified as a noncancer, would you stop surveillance? What will you prefer as a next biopsy--transperineal to avoid the risk of sepsis and other infections or transrectal which may cause less immediate pain? Conclusions: We intend that the results will inform decision making as to the classification of Gleason 6 diagnoses.
Validation of baseline health-related quality of life as prognostic indicator for survival outcome in men with intermediate risk prostate cancer undergoing radical prostatectomy.
Authors: Westhofen Thilo , Buchner Alexander , Schlenker Boris , Becker Armin , Stief Christian G. , Kretschmer Alexander
Published: March 2023

340

Background: Accurate prediction of cancer outcomes remains a key component of prostate cancer (PC) treatment decision-making. Intermediate-risk PC patients represent a heterogeneous group with highly variable prognoses and it is challenging to provide uniform treatment recommendations for those patients. Previous studies have shown baseline health-related quality of life (HRQOL) to be a robust prognostic indicator for survival outcomes of different cancer entities in the metastatic setting, with scarce evidence on PC. We therefore sought to validate the predictive value of baseline HRQOL for survival outcomes in men with intermediate risk PC undergoing radical prostatectomy (RP). Methods: We identified 4780 patients with intermediate risk PC according to NCCN risk stratification and prospectively assessed baseline HRQOL prior RP. Patients were stratified by global health status (GHS) domain of the QLQ-C30 questionnaire. Oncologic endpoints were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox regression models were applied to assess the predictive value of baseline GHS on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model. Decision curve analysis (DCA) was performed to validate the clinical net benefit associated with adding GHS to our multivariable model ( P < .05). Results: Median follow up was 51mo. In multivariable analysis, GHS was confirmed as an independent predictor for increased MFS (HR .98, 95% CI .97-.99; P = .028) and OS (HR .97, 95% CI .95-.99; P = .008), indicating a relative risk reduction of 1.7% for MFS and 2.8% for OS per 1-point increase of baseline GHS. Adding GHS to our model improved predictive accuracy of prognosis for MFS by 6% (c-index .75 vs .72) and for OS by 8% (c-index .78 vs .74). Validation with DCA revealed a net benefit over all thresholds in prediction of MFS and OS when adding GHS to our model. Conclusions: Our findings highlight that baseline HRQOL is a valuable and robust prognostic factor for patients with intermediate-risk PC prior RP. Baseline HRQOL data improve prognostic accuracy of MFS and OS and can therefore support treatment decision-making. [Table: see text]
Development and validation of a multi-institutional nomogram of outcomes for PSMA-PET–based salvage radiotherapy in recurrent prostate cancer.
Authors: Zamboglou Constantinos , Arnoux Armelle , Janbain Ali , Strouthos Iosif , Farolfi Andrea , Koerber Stefan , Peeken Jan , Vogel Marco , Ferentinos Konstantinos , Shelan Mohamed , Grosu Anca L. , Kroeze Stephanie , Guckenberger Matthias , Fanti Stefano , Hruby George , Scharl Sophia , Wiegel Thomas , Henkeberens Christoph , Emmett Louise , Hegemann Nina-Sophie
Published: March 2023

355

Background: We aimed to develop and to validate a multi-institutional nomogram of outcomes for PSMA-PET based salvage radiotherapy (sRT) following radical prostatectomy (RP) for patients with recurrent or persistent prostate cancer (PCa). Methods: Data from patients with a detectable post-RP prostate-specific antigen (PSA) treated with sRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 11 academic institutions from 5 countries. All patients had a PSMA-PET scan prior sRT and patients with distant metastases on PET were excluded from this analysis. The freedom from biochemical failure (FFBF) rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse (BR) was defined as PSA nadir +0.2 ng/ml after sRT. Results: Overall, 1029 patients (training set n=821, external validation set n=208) with a median follow-up of 33 months were included. On PSMA-PET, 427 (42%) and 313 (30%) patients had local and nodal recurrences, respectively. Elective pelvic lymphatics were irradiated in 368 (36%) patients. All patients received sRT to the prostatic fossa receiving a dose of <66 Gy, 66-70 Gy and >70 Gy in 103 (10%), 551 (54%) and 375 (36%) patients, respectively. Androgen deprivation therapy (ADT) was given in 325 (32%) patients. On multivariable Cox regression analysis, pre-SRT PSA, ISUP grade, pT stage, surgical margins, ADT use, sRT dose and nodal recurrence on PSMA PET were associated with FFBF. The nomogram concordance index was 0.7 for FFBF in external validation. Conclusions: We present an externally validated contemporary nomogram which can estimate individual patient outcomes after PSMA-PET guided sRT. Positive lymph nodes on PSMA-PET seem to be a new risk factor for BR after sRT.
Biochemical disease control outcomes of stereotactic body radiation therapy (SBRT) or moderate hypo-fractionation (HFRT) for low- and intermediate-risk prostate cancer (PrCa): Retrospective analysis of 12 years of experience at two Canadian cancer centers.
Authors: Hu Hsin-pei (Spencer) , Gouran-Savadkoohi Mohammad , Anagnostopoulos Gregory , Dayes Ian S. , Ishkanian Adrian , Hallock Abhirami , Corbett Thomas B , Lukka Himanshu , Quan Kimmen , Schnarr Kara , Cuthbert David , Goldberg Mira , Tsakiridis Theodoros
Published: March 2023

363

Background: SBRT uses highly conformal radiotherapy to deliver high dose per fraction treatment. Advantages of SBRT include short treatment times, decreased costs and limited toxicity. Randomized trial outcomes of 7-fraction SBRT for low or intermediate PrCa were reported but results of studies that compared 5-fraction SBRT with conventional and HFRT are pending. Here, we reviewed the 12-year experience with SBRT and HFRT at the Juravinski and Walker Family Cancer Centers in Ontario. Methods: We reviewed patients with low or intermittent-risk PrCa treated with SBRT alone or HFRT alone in the period of July 2010 and February 2022. Database search criteria included treatments with SBRT 35-40Gy in 5 fractions and HFRT 60-62Gy in 20 fractions. Overall survival (OS), time to biochemical failure (per Phoenix criteria: i.e., 2ng/mL above PSA nadir) and biochemical failure-free survival (bFFS) were reviewed. Kaplan-Meier curves were used to assess OS and bFFS. Results: We identified 314 patients with low or intermediate-risk PrCa who were treated with SBRT and 258 patients who were treated with HFRT. Intermediate-risk category composed 86.0% and 95.7% of the SBRT and HFRT cohorts. ISUP Grade Group (GG) distributions for the SBRT and HFRT patients were: GG1: 19.4% and 9.3%, GG2: 72.9% and 74.0%, and GG3: 7.6% and 16.7%, respectively. OS rates at 5 years were 96.6% for SBRT vs. 95.8% for HFRT-treated patients. The 5-year bFFS rates for SBRT and HFRT were 92.3% and 90.1%, respectively. The 7-year bFFS rate for the SBRT cohort was 90.2%. Mean time to biochemical failure was 40.4 months after SBRT vs. 35.8 months after HFRT. Conclusions: SBRT is an effective treatment option for low to intermediate-risk PrCa with encouraging OS and bFFS rates comparable with HFRT. Pending randomized trial results will determine whether SBRT is the new standard of care for this population.
Stereotactic reirradiation for local prostate cancer recurrence: Mono-institutional experience of 108 patients.
Authors: Baty Manon , Castelli Joel , Gnep Khemara , Delaby Nolwenn , Mathieu Romain , de Crevoisier Renaud
Published: March 2023

365

Background: The aim of this study was to report the efficacy and toxicity of salvage stereotactic body radiation therapy (SBRT) for local prostate cancer recurrence after radiotherapy. Methods: We retrospectively reviewed a total of 108 medical records of patients treated with salvage SBRT for prostate cancer recurrence, between July 2015 and February 2021 in our institution. Patients who had initial radical prostatectomy were excluded. The median time interval between the two radiation treatments was 9 years (range, 3-20 years). All the patients had biochemical recurrence, with a PSA of 3.5 ng/mL (range, 1.8-43 ng/mL). Local recurrence was to be proven by biopsies, without distant lymph node or metastasis. The local recurrence was visible in 82% and 99% of patients on mpMRI and choline/PSMA PET/CT, respectively. The salvage treatment consisted in SBRT at a total dose of 36 Gy in six fractions delivered every other day, associated with androgen deprivation therapy in 44% of patients. We reported efficacy and toxicity (according to CTCAE v 4.03 classification) after salvage SBRT. Results: Median follow-up was 19.6 months (range, 2.3-67 months). Two year biochemical recurrence-free survival and lymph node/metastases free survival rates were 76% (95% CI: 66-87%) and 88% (95% CI: 80-96%), respectively. Regarding acute toxicity, rates of grade 2 and 3 GU toxicities were 27% and 2%, respectively. Rate of grade 2 GI toxicity was 2%, without grade ≥3. Regarding late toxicity, 2 year rates of grade 2 and 3 GU toxicities were 50% (95% CI: 44-56%) and 8% (95% CI: 2-14%), respectively. One patient experimented a grade 4 GU toxicity (bladder necrosis requiring a cystectomy) 8 months after SBRT. Two year rate of grade 2 GI toxicity was 2 (95% CI: 0-5%), without grade ≥3. Conclusions: The main toxicity of prostate salvage SBRT is GU. With a short follow-up, a subset of patients may be controlled by the salvage treatment.