Time Of Prostate Cancer Diagnosis Research Articles

Sociodemographic predictors of the late-stage diagnosis in patients with prostate cancer: A retrospective cohort study.

132 Background: Distant metastasis at the time of prostate cancer (PCa) diagnosis is associated with increased morbidity and mortality. This study aimed to assess the impact of sociodemographic characteristics on distant metastasis at the time of PCa diagnosis. Methods: The Surveillance Epidemiology and End Results (SEER) database (2000-2021), including PCa patients from 17 registries, was queried. Patients with late-stage diagnosis (LSD) were defined as those who were initially diagnosed with stage IV disease, indicating distant metastasis. Sociodemographic predictors included race, ethnicity, age, marital status, residential status, and median household income. Multicollinearity was assessed using variance inflation factors (VIF). Univariable logistic regression was performed to identify significant predictors of LSD, which were further analyzed in multivariable logistic regression using a maximum likelihood estimation approach. Odds ratios with 95% confidence intervals (CI) were computed with a p-value of <0.05 indicating a statistically significant association. Results: Of the 1,089,736 PCa patients diagnosed, 64,983 (6%) had an LSD. The majority were white (80%), non-Hispanic/Latino (HL) (91%), aged ≥65 years (60%), married (75%), residents in metropolitan areas (88%), and had an annual house income of ≥$70,000 (70%). Multivariable logistic regression identified Black (OR: 1.24; 95%CI: 1.22-1.27), Asian or Pacific Islander (1.35; 1.30-1.40), and American Indian/Alaska Native (1.70; 1.53-1.89) to have higher odds of LSD compared to White patients (Table). In addition, HL ethnicity compared to non-HL (OR: 1.45; 95% CI: 1.42-1.49), age ≥65 compared to <65 (1.68; 1.65-1.71), unmarried status compared to married (1.88; 1.85-1.91), residency in non-metropolitan areas compared to metropolitan (1.10; 1.07-1.12), and household income <$70,000 compared to ≥$70,000 (1.03; 1.01-1.05) had a significant association with LSD. Conclusions: Older, non-White (Black, Asian/Pacific Islander, American Indian/Alaska Native), Hispanic/Latino, unmarried men, residents of non-metropolitan areas, or those with lower annual household incomes have higher odds of late-stage diagnosis. Interventions targeting early detection in these at-risk groups may improve prostate cancer outcomes in the US. Variable Odds Ratio (95% CI) p-value Race (Black vs White) 1.24 (1.22-1.27) <0.01 Race (Asian or Pacific Islander vs White) 1.35 (1.31-1.40) <0.01 Race (American Indian/Alaska Native vs White) 1.70 (1.53-1.89) <0.01 Ethnicity (Hispanic/Latino vs non-/Hispanic/Latino) 1.45 (1.42-1.49) <0.01 Age (≥65 vs <65) 1.68 (1.65-1.71) <0.01 Marital status (unmarried vs married) 1.88 (1.85-1.91) <0.01 Residence status (non-metropolitan vs metropolitan) 1.10 (1.07-1.12) <0.01 Household income (<$70,000 vs ≥$70,000) 1.03 (1.01-1.05) <0.01

Testosterone levels at diagnosis: A key predictor of overall survival among patients with prostate cancer.

The exact relationship between testosterone levels at diagnosis and prostate cancer (PCa) prognosis remains inadequately explored. The objective was to determine whether serum testosterone levels at the time of PCa diagnosis are associated with overall survival. The study cohort involved 2544 PCa patients, divided into three groups; normal (>10.4nmol/L), grey zone (8.0-10.4nmol/L) and low (2.0-8.0nmol/L) serum testosterone groups. Survival outcomes were analysed using Kaplan-Meier curves and Cox regression models. The analysis revealed an increased risk of death among patients with low testosterone levels compared to those with normal levels in uni- (HR = 1.67, 95% CI: 1.37-2.05, p < 0.001) and multivariable-adjusted (HR = 1.58, 95% CI: 1.24-1.98, p < 0.001) analysis. Sensitivity analysis on patients with normal glucose metabolism revealed similar results (HR = 1.93, CI: 1.48-2.51, p < 0.001), as well as after stratified with age below 70 years (HR = 1.55, 95% CI: 1.02-2.36, p < 0.001) and over 70 years (HR = 1.83, 95% CI: 1.46-2.28, p < 0.001.) There was no difference in survival between the grey zone compared to other testosterone groups. The retrospective design limits our ability to infer causality. Low testosterone at the time of PCa diagnosis is an independent predictor of overall survival. Findings highlight the potential of testosterone for prognostic evaluation in PCa.

Immunohistochemical Analysis of Androgen Receptor Expression Predicts the Prognosis of Metastatic Castration-Sensitive Prostate Cancer Patients Receiving Abiraterone Acetate.

The efficacy of abiraterone acetate varies among patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Both androgen receptor (AR) and cytokeratin 18 (CK18) are markers of the luminal lineage of prostate cancer, and their expression levels have been suggested to affect the response to androgen deprivation therapy (ADT). This study aimed to predict the efficacy of abiraterone acetate in high-risk mCSPC via immunohistochemical staining of biopsy specimens obtained at the time of prostate cancer diagnosis. We retrospectively analyzed 44 patients treated with abiraterone acetate in combination with ADT. AR and CK18 expression in prostate biopsy specimens were assessed using immunohistochemical staining. AR and CK18 staining was not significantly associated with overall survival (OS). However, low AR staining was significantly associated with a shorter time to castration-resistant prostate cancer (TTCRPC) compared with high AR staining (log-rank test, p = 0.018). Similarly, low CK18 staining was significantly associated with a shorter TTCRPC compared with high CK18 staining (log-rank test, p = 0.037). Immunohistochemical analysis of AR or CK18 expression in biopsy specimens may serve as a predictive biomarker of high-risk mCSPC treated with abiraterone acetate. None.

Androgen deprivation therapy and cardiological risks in patients with prostate cancer. Are all drugs the same?

Prostate cancer (PCa) is the most common oncological disease in men in Russia. For a long time, long-term androgen deprivation therapy (ADT) decreasing native testosterone level has been the basis of PCa drug therapy. At the time of PCa diagnosis, 2/3 of men have various risk factors for cardiovascular diseases (CVDs) or established CVDs (one fourth of the patients have CVDs associated with atherosclerosis; 45 % have a diagnosis of arterial hypertension). ADT is associated with increased risk of CVD and cardiovascular complications (CVC) development. Patients with PCa die of 2 main causes: directly due to cancer or due to CVD. Previously, luteinizing hormone-releasing hormone (LHRH) antagonists were considered to have a better safety profile compared to LHRH agonists. Comparison of all LHRH agonists (leuprorelin, triptorelin, goserelin, buserelin) with LHRH antagonists in meta-analyses showed that the risk of serious CVCs during LHRH antagonist therapy was 43 % lower than during agonist therapy. However, comparison of leuprorelin with antagonists did not show a significant difference in CVC rate. Leuprorelin is a drug with the most favorable profile of cardiological safety among the ADT drugs and the most frequently used LHRH agonist in the world. Considering high risk of CVDs and CVCs in patients with PCa, along with treatment of the main disease, careful control and reduction of risks of CVD development from the moment of PCa diagnosis should be implemented, the patients must be informed on the necessity of healthy lifestyle, established CVDs should be treated with rational regimens of antihypertensive, hypolipidemic, and hypoglycemic drugs. Risk control and reduction, as well as CVD treatment, should be performed for the whole duration of ADT. The article proposes an algorithm of cardiometabolic risk stratification prior to ADT initiation and during ADT.

Serum Calcium Level at Diagnosis Can Predict Lethal Prostate Cancer Relapse.

Background/Objectives: The most important prognostic factors in curatively treated prostate cancer are T and N stage, histology, grade group and initial PSA. A recent study found that men with blood calcium levels at the high end of the normal range are over two-and-a-half times more likely to develop fatal prostate cancer than those with lower calcium levels. However, there is limited evidence regarding the prognostic value of calcium levels at the time of prostate cancer diagnosis. We aimed to determine whether a calcium level in the upper range of normal values has any prognostic value in curatively treated prostate cancer. Methods: We conducted a retrospective analysis of 84 consecutive patients with prostate cancer who underwent curative-intent radiotherapy-either as primary treatment or adjuvant therapy-using external beam radiotherapy with or without brachytherapy. We analyzed all pertinent prognostic factors that could potentially impact disease-free survival. Results: The study revealed that calcium levels at diagnosis significantly predict disease-free survival, whereas the initial PSA level did not hold prognostic significance-likely due to interference from benign prostatic hyperplasia. Conclusions: If our findings are validated, calcium levels at the time of prostate cancer diagnosis could be incorporated into future predictive and prognostic models.

177 Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration-Resistant Metastatic Prostate cancer.

A patient with widespread intensely prostate-specific membrane antigen-expressing, BRCA gene mutation-positive bone metastases at the time of prostate cancer diagnosis had progressed on multiple lines of standard therapy. He received 177 Lu-prostate-specific membrane antigen 8.5 GBq augmented by a short course of olaparib radiosensitization and achieved 90% decrease in serum PSA level after a single treatment. His tumor response was much better than expected by predictive dosimetry. However, his marrow radiotoxicity was worse than anticipated and required hospitalization. This suggests radiosensitizing agents to be a double-edged sword that must be carefully considered and balanced during activity prescription.

Temporal trends in medication and service use patterns for mental health issues among men with prostate cancer.

Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5years before and 5years after prostate cancer diagnosis. Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n=13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns. Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5years before to 40.3% 5years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2years following prostate cancer diagnosis. There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention.

Differential Tumor Gene Expression Profiling of Patients With Prostate Adenocarcinoma on the Basis of BMI.

An increased BMI is linked to increased prostate adenocarcinoma incidence and mortality. Baseline tumor gene expression profiling (GEP) can provide a comprehensive picture of the biological processes related to treatment response and disease progression. We interrogate and validate the underlying differences in tumor GEP on the basis of BMI in patients with prostate adenocarcinoma. The inclusion criteria consisted of histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data obtained from treatment-naïve primary prostate tissue. RNA sequencing was performed by a Clinical Laboratory Improvement Amendments-certified laboratory (Tempus or Caris Life Sciences). The Tempus cohort was used for interrogation and the Caris cohort for validation. Patients were stratified on the basis of BMI at the time of prostate cancer diagnosis: BMI-high (BMIH; BMI ≥30) and BMI-low (BMIL; BMI <30). Differential gene expression analysis between the two cohorts was conducted using the DEseq2 pipeline. The resulting GEPs were further analyzed using Gene Set Enrichment software to identify pathways that exhibited enrichment in each cohort. Overall, 102 patients were eligible, with 60 patients in the Tempus cohort (BMIL = 38, BMIH = 22) and 42 patients in the Caris cohort (BMIL = 24, BMIH = 18). Tumor tissues obtained from patients in the BMIL group exhibited higher expression of genes associated with inflammation pathways. BMIH displayed increased expression of genes involved in pathways such as heme metabolism and androgen response. Our study shows the upregulation of distinct genomic pathways in BMIL compared with BMIH patients with prostate cancer. These hypothesis-generating data could explain different survival outcomes in both groups and guide personalized therapy for men with prostate cancer.

Abstract C125: Prostate specific antigen testing patterns and prostate cancer stage at diagnosis in Ohio cancer patients

Abstract Summary Statement This study aims to: 1) examine patterns of prostate specific antigen (PSA) testing — diagnostic or screening — across subgroups of prostate cancer (PCa) patients; and 2) analyze patterns of PSA testing in relation to PCa stage at diagnosis. Background Recommendations for PSA tests, blood-based screenings used for PCa detection, are issued by the United States Preventive Services Task Force. Changes in national recommendations, as well as demographic and clinical information can influence the likelihood of an individual receiving a PSA test, and the subsequent PCa diagnosis. Methods Using data from the 2014-2016 linked Ohio Cancer Incidence Surveillance System (OCISS) and Medicare database, we categorized PSA testing as diagnostic or screening, based on diagnosis and procedure codes. Bivariate analyses were conducted on several factors, including patient demographics, claims-based frailty measures, and certain social determinants of health, to evaluate their association with receipt of screening PSA and stage of PCa diagnosis. Two multivariable logistic regression models were created to identify factors associated with receipt of screening PSA test, and subsequently, of being diagnosed with distant stage PCa. Results After excluding individuals identified without any PSA testing in the three years prior to diagnosis (n = 964) and those with unknown staged cancer (n = 446), our final study population included 3034 Ohio men diagnosed with PCa between 2014-2016. The median age was 73 years. Being of older age at the time of PCa diagnosis (adjusted odds ratio (aOR): 0.95 [95% confidence interval: 0.94, 0.97]) was associated with significantly lower odds of being screened. Compared to non-frail men, pre-frail patients (aOR: 0.69 [0.57, 0.84]) and patients with mild to severe frailty (aOR: 0.54 [0.39, 0.75]) also had decreased odds of being screened. History of receipt of screening PSA tests was associated with lower odds of being diagnosed with distant stage disease (aOR: 0.55 [0.42, 0.72]). On the other hand, being of older age at the time of PCa diagnosis (aOR: 1.14 [1.12, 1.17]), having moderate to severe frailty (compared to non-frailty) (aOR: 4.30 [2.38, 8.02]), and being separated or divorced (compared to being married) (aOR: 1.75 [1.06, 2.78]), were associated with increased odds of being diagnosed with distant stage disease. Conclusions Younger age and lower gradients of frailty were strongly associated with receipt of screening PSA. In turn, receipt of screening PSA was associated with early stage PCa, while being older, having higher degrees of frailty, and being divorced or separated from a spouse, were associated with elevated odds of distant stage PCa. This study adds to existing evidence suggesting that PSA-based screening may promote earlier detection of prostate cancer in a real-world setting and challenges preexisting beliefs on the usefulness of PSA testing in older populations. Citation Format: Sajan Patel, Siran Koroukian, Johnie Rose, Long Vu, Holly Hartman. Prostate specific antigen testing patterns and prostate cancer stage at diagnosis in Ohio cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C125.

Low PSA radiographic disease progression on C11-choline PET.

For men with prostate cancer, radiographic progression may occur without a concordant rise in prostate-specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C-11 choline positron emission tomography (PET) imaging in patients achieving ultra-low PSA values and to evaluate clinical outcomes in this patient population. In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C-11 choline PET scan while the PSA value was less than 0.5ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan-Meier method. Intergroup differences were assessed using the log-rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP. A total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7-106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration-resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small-cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow-up of 49.4 (21.3-95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log-rank) as compared with other sites of rDP. Men with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

Longitudinal change in castration-resistant prostate cancer biomarker AST/ALT ratio reflects tumor progression

We investigated whether aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio and its change during the course of treatment in castration-resistant prostate cancer (CRPC) patients is associated with tumor condition and lethality. Clinical data from 130 CRPC patients were retrospectively evaluated. AST/ALT ratios at the time of prostate cancer (PC) diagnosis, androgen deprivation therapy (ADT), CRPC diagnosis, and the final follow-up examination after CRPC treatment were calculated for each. The prognostic capabilities of the AST/ALT ratio for overall survival (OS) were analyzed by use of the Kaplan–Meier method and Cox hazard models. The median AST/ALT ratio at PC diagnosis was 1.517 and the optimal value predicting lethality defined by the receiver operating curve was 1.467. The AST/ALT ratio decreased once during ADT and then elevated in a stepwise manner with cancer progression. In surviving patients, the median AST/ALT ratio at the time of PC diagnosis was 1.423, which did not change longitudinally, whereas that in patients later deceased was significantly higher (1.620) and further elevated after CRPC diagnosis. Kaplan–Meier curves indicated significantly worse OS in patients with an AST/ALT ratio ≥ 1.467, which was confirmed by multivariate analysis. These findings indicate AST/ALT ratio as a prognostic biomarker for CRPC with longitudinal changes reflecting tumor progression.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p=.03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Abstract B129: Workplace accommodations during and after prostate cancer treatment

Abstract This study was designed to examine the modifications and accommodations African-American and White prostate cancer survivors experience at their workplaces during and following radiation therapy or a prostatectomy. Approximately 1 in 8 men will be diagnosed with prostate cancer. Although the average age at time of prostate cancer diagnosis is 66, the substantial number of younger men diagnosed results in large number of men facing treatment during their working years. African-American men are disproportionately affected by prostate cancer; understanding their experiences is therefore particularly vital. Forty-five prostate cancer survivors who had undergone radiation therapy or a prostatectomy within the past 6-36 months, had worked within one month prior to treatment initiation, and had expected to be working six months in six months participated in semi-structured, in-depth interviews about their experiences at work prior to, during, and after treatment. The audio-recorded interviews were transcribed and systematically analyzed. Twenty of the participants were African-American men and 25 were White men, and their mean age was 61. Most men were able to receive accommodations to address their needs in addition to time off for treatment and recovery if needed. These accommodations included temporarily changing their jobs duties so that they could focus on tasks that eliminated or reduced the most physically demanding aspects of their jobs such lifting heavy objects, performing tasks that could be conducted while seated, and reducing work-related travel. Working from home, reducing their work hours, and taking breaks during the work day also benefited some survivors. Although rare, a man who experienced difficulty meeting the physical demands of his job lacked accommodations and was afraid to request any due to his concern that he would lose his job. Men who lacked access to conveniently placed bathrooms used creative strategies. The move to have employees working at home and eliminating or reducing work-related travel due to the COVID-19 enabled some workers to forgo some accommodations they would have otherwise required. Variation in experience by race will be addressed. The needs of and workplace accommodations provided to prostate cancer survivors undergoing and recovering from prostate cancer treatment vary widely. Increased attention to their needs and strategies to address them could enable prostate cancer survivors to be better prepared for work-related challenges. Citation Format: Joanne C. Sandberg, Otis L. Owens. Workplace accommodations during and after prostate cancer treatment [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B129.

Evaluation of PSMA-PET Biology-Guided Radiotherapy Sequential Boost to the PSMA-avid Subvolume in the Prostate Region in Low-Volume Advanced Prostate Cancer

Evaluation of PSMA-PET Biology-Guided Radiotherapy Sequential Boost to the PSMA-avid Subvolume in the Prostate Region in Low-Volume Advanced Prostate Cancer

The prognostic value of digital rectal exam for the existence of advanced pathologic features after prostatectomy.

Accurate staging at the time of prostate cancer diagnosis is fundamental to risk stratification and management counseling. Digital rectal exam (DRE) is foundational in clinical staging of prostate cancer, even with a known limited interexaminer agreement and poor sensitivity for detecting extraprostatic disease. We sought to evaluate the prognostic value of DRE for the presence of advanced pathologic features (APFs) following radical prostatectomy (RP). All patients undergoing RP as primary treatment for clinically localized prostate cancer in the National Cancer Database between 2008 and 2014 were identified. Patients with additional malignancies, prior treatment with radiation or systemic therapy, incongruent clinical staging and DRE findings or without fully evaluable clinical staging were excluded. The primary outcome was the presence of postsurgical APFs, defined as positive surgical margins, nodal disease, or pathologic stage T3 or greater. Multivariable logistic regression analysis was performed to account for prostate-specific antigen (PSA), biopsy grade group, percent of positive biopsy cores, and clinical stage. In total, 91,525 patients consisting of 69,182 cT1, 20,641 cT2, and 1702 cT3-T4 were included. The average age was 61.1 ± 7.0 years, and the average PSA was 8.6 ± 10.3 ng/ml. On multivariable analysis, cT3 and T4 were associated with the presence of APFs (odds ratio [OR] 11.12, p < .01 and 5.28, p = .04), however, cT2 was only slightly associated with the presence of APFs when compared with cT1 (OR 1.15, p < .01). Furthermore, cT2 was associated with more node-positive disease (OR 1.63, p < .01), positive margins (OR 1.06, p < .01), and more than or equal to pT3 disease (OR 1.22, p < .01). Overall, advanced clinical stage as assessed by DRE was independently associated with an increasing risk of APFs. For individual APFs, the greatest effect is noticed between clinical stage and nodal positivity and less so between clinical stage and positive margins. DRE continues to hold value, particularly for patients with locally advanced disease and potential lymph node disease.

Baseline Testosterone Levels in Men with Clinically Localized High-Risk Prostate Cancer Treated with Radical Prostatectomy with or without Neoadjuvant Chemohormonal Therapy (Alliance).

Baseline Testosterone Levels in Men with Clinically Localized High-Risk Prostate Cancer Treated with Radical Prostatectomy with or without Neoadjuvant Chemohormonal Therapy (Alliance).

Abstract PO003: CD38 in the advanced prostate cancer

Abstract Background: CD38, an ecto-enzyme involved in adenosine synthesis, is implicated in tumor immune evasion. Its expression and role in the prostate tumor microenvironment (TME) has not been fully elucidated. Main objectives: To determine whether CD38 is associated with prostate cancer (PC) immune evasion, to characterize CD38 expression on PC epithelial cells and tumor infiltrating immune cells (TIICs) as tumors progress from castration-sensitive PC (CSPC) to metastatic castration-resistant PC (mCRPC), and to determine the association between CD38+ TIICs and survival. Methods: Data from 159 mCRPC transcriptomes from the Stand Up To Cancer/Prostate Cancer Foundation cohort were analyzed for associations between CD38 and 200 cell signaling pathways, an adenosine signature and T cell exhaustion signatures. CD38 protein expression on tumor epithelial cells and TIICs was scored using validated immunohistochemistry (IHC) assays on 51 treatment-naïve CSPC biopsies and matching, same-patient mCRPC biopsies obtained between 2016-2018 from men treated at The Royal Marsden Hospital. To characterize CD38+ TIICs, CD38 co-expression with immune cell surface markers for T cells (CD3), B cells (CD19, CD20, CD138, CD79a), and myeloid cells (CD11b, CD15, CD33) was determined by dual-color IHC or multiplex immunofluorescence. The change in CD38+ TIICs density from CSPC to mCRCP was assessed by negative binomial regression and the associations between CD38+ TIIC density and survival were studied using Kaplan-Meier methods, Cox regression and the log-rank test. Results: Unbiased transcriptome analyses showed that CD38 mRNA expression in mCRPC was associated with upregulated immune signaling pathways, with the ten pathways showing the strongest evidence of association (all P &amp;lt; 1 × 10^-10) with CD38 mRNA expression all being immunomodulatory. CD38 expression was associated with IL-23 signaling (P &amp;lt; 1 × 10^-10), a myeloid suppressor cell-derived mediator of endocrine resistance, as well as immunosuppressive adenosine signaling (P &amp;lt; 1 × 10^-8) and T cell exhaustion signatures (P &amp;lt; 1 × 10^-10). CD38 protein was largely absent from tumor epithelial cells (7.7%). CD38 was expressed by phenotypically diverse TIICs. CD38+ TIICs co-expressed myeloid cell surface markers (CD33, CD15), B cell surface markers (CD19, CD20, CD79a, CD138), and the T cell surface marker (CD3). CD38+ TIIC density increased as tumors progressed from CSPC to CRPC (negative binomial regression, P = 0.03). CSPC and CRPC with higher CD38+ TIIC density (dichotomized based on the median; &amp;gt; 1.5 cells/mm^2) were associated with shorter overall survival from the time of PC diagnosis (hazard ratio [HR]: 1.89; 95% CI: 1.02-3.50) and the time of mCRPC biopsy (HR: 2.14; 95% CI: 1.15-4.00), respectively. Conclusion: CD38 is expressed by diverse TIICs in the prostate TME and was associated with potential mechanisms of immune evasion. CD38 expression may serve as a potential prognostic biomarker and therapeutic target in PC aimed at overcoming PC immunoresistance. Citation Format: Christina Guo, Mateus Crespo, Bora Gurel, David Dolling, Jan Rekowski, Adam Sharp, Antonella Petremolo, Semini Sumanasuriya, Daniel N. Rodrigues, Ana Ferreira, Rita Pereira, Ines Figueiredo, Niven Mehra, Maryou B.K. Lambros, Antje Neeb, Veronica Gil, Leon Terstappen, Andrea Alimonti, Charles G. Drake, Wei Yuan, Johann S. de Bono. CD38 in the advanced prostate cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO003.

Suitability of PSMA-PET Biology-Guided Radiotherapy for Low Volume Metastases in Newly Diagnosed Prostate Cancer

Suitability of PSMA-PET Biology-Guided Radiotherapy for Low Volume Metastases in Newly Diagnosed Prostate Cancer

Comparison of cross-sectional imaging techniques for the detection of prostate cancer lymph node metastasis: a critical review.

Conventional staging for prostate cancer (PCa) is performed for men diagnosed with unfavorable-intermediate or higher risk disease. Computed tomography (CT) of the abdomen and pelvis and whole body bone scan remains the standard of care for the detection of visceral, nodal, and bone metastasis. The implementation of the 2012 United States Preventive Services Task Force recommendation against routine prostate specific antigen (PSA) screening resulted in a rise of metastatic PCa at the time of diagnosis, emphasizing the importance of effective imaging modalities for evaluating metastatic disease. CT plays a major role in clinical staging at the time of PCa diagnosis, but multi-parametric magnetic resonance imaging (MRI) is now integrated into many prostate biopsy protocols for the detection of primary PCa, and may be a surrogate for CT for nodal staging. Current guidelines incorporate both CT and MRI as appropriate cross-sectional imaging modalities for the identification of nodal metastasis in indicated patients. There is an ongoing debate about the utility of traditional cross-sectional imaging modalities as well as advanced imaging modalities in detection of both organ-confined PCa detection and nodal involvement.

Changes in prostate-specific antigen at the time of prostate cancer diagnosis after Medicaid expansion in young men.

The objective of this study was to determine the effect of Medicaid expansion under the Patient Protection and Affordable Care Act (January 1, 2014) on the epidemiology of high-risk prostate-specific antigen (PSA) levels (≥20ng/mL) at the time of prostate cancer (PCa) diagnosis. The authors hypothesized that better access to care would result in a reduction of high-risk features at diagnosis. A retrospective cohort study was performed of 122,324 men aged <65years who were diagnosed with PCa within the National Cancer Database. Difference-in-difference (DID) analyses adjusting for sociodemographic variables using linear regression compared PSA levels at diagnosis before expansion (2012-2013) and after expansion (2015-2016) between men residing in states that did or did not expand Medicaid. From 2012 to 2016, the proportion of men with PSA levels ≥20ng/mL increased (from 18.9% to 19.8%) in nonexpansion states and decreased (from 19.9% to 18.2%) in expansion states. Compared with men in nonexpansion states, men in expansion states experienced a decline in PSA ≥20ng/mL (DID, -2.33%; 95% CI, -3.21% to -1.44%; P<.001). Accordingly, the proportion of men presenting with high-risk disease decreased in expansion states relative to nonexpansion states (DID, -1.25%; 95% CI, -2.26% to 0.25%; P=.015). A similar statistically significant decrease in PSA levels ≥20ng/mL was noted among black men (DID, -3.11%; 95% CI, -5.25% to 0.96%; P=.005). In Medicaid expansion states, there was an associated decrease in the proportion of young men presenting with PSA ≥20ng/mL at the time of PCa diagnosis. These results suggest that Medicaid expansion improved access to PCa screening. Longer term data should assess oncologic outcomes.