Time Of Prostate Cancer Diagnosis Research Articles

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

Biology-guided radiation therapy (BgRT) is a new technology that aims to deliver radiation based on detecting positron emissions in real time. BgRT combined with prostate specific membrane antigen (PSMA) PET/CT imaging may be an attractive option for prostate cancer patients with low-volume pelvic nodes and distant metastases since all lesions may be treated during the same session. This study investigates the feasibility of BgRT sequential boost to the PSMA-avid subvolume (PAS) in the prostate region. The ratio of standard uptake value (SUV) to background SUV is quantified, with specific focus on adjacent bladder uptake.Patients enrolled in the ProPSMA prospective single-institution clinical trial underwent Ga-68-PSMA-11 PET scan at the time of prostate cancer diagnosis. Those with pelvic node or distant metastases were selected for analysis. PAS gross target volume (GTV) was delineated on the PET component of a PET/CT acquisition by using a PET edge tool in commercially available software. Three dimensional shells of thickness 5 mm, 10 mm and 20 mm were created by expanding the GTV to characterize the uptake background and to determine suitability of BgRT based on these tracking zones. Normalized SUV (nSUV) was calculated as the ratio of SUVmax in the GTV to SUVmean of the adjacent shell. Lesions with nSUV larger than 3 were defined to be suitable for BgRT. An increase in nSUV with increasing shell thickness indicates absence of uptake surrounding the GTV.From the ProPSMA patient cohort of 89 patients, 24 patients had at least one pelvic nodal or distant metastases. PAS GTV volume ranged from 1 cc to 147 cc (median = 25 cc, IQR = 12 cc - 62 cc). GTV SUVmax varied from 6.4 to 80 (median = 21.5; IQR = 14 - 33). nSUV ranged from 3.4 to 21.2 (median = 6.4; IQR = 4.9 - 8.5), from 4.1 to 20.9 (median = 8.6; IQR = 6 - 10.5), and from 2.8 to 31.4 (median = 8.2; IQR = 5.4 - 13.8) in 5 mm, 10 mm, and 20 mm shell, respectively. Moreover, 100%, 100%, and 96% of lesions had nSUV greater than 3 in a shell thickness of 5 mm, 10 mm, and 20 mm, respectively. nSUV increased from the 5 mm shell to the 10 mm shell in 75% of patients and from the 10 mm shell to the 20 mm in 46% patients, indicating the absence of bladder uptake.An nSUV greater than 3 was achieved in more than 95% of all GTVs for all shell thicknesses investigated in this study, which suggests that PSMA-guided BgRT is a feasible modality for sequential boost directed at the dPSMA-avid subvolume in the prostate region. If bladder proximity impacts geometric specificity of BgRT delivery or if greater tumor-to-background contrast is desired, additional refinements may be required. These may include modifications to the BgRT algorithm that enable masking of the bladder. Clinical trial number ACTRN12617000005358.

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).

Men with low serum testosterone at the time of prostate cancer diagnosis are frequently considered to have more aggressive disease. We examined treatment outcomes in men with clinically localized high-risk cancer to determine if baseline testosterone level identified men at higher risk for cancer progression after treatment. Alliance/CALGB 90203 randomized men with clinically localized high-risk prostate cancer to radical prostatectomy alone or neoadjuvant chemohormonal therapy and radical prostatectomy. Men with available baseline testosterone levels who had not received androgen deprivation prior to study enrollment were studied (656). Testosterone level was examined as a continuous variable, as quartiles, and separately in men with an absolute testosterone level above/below 150 ng/dl. Outcomes evaluated were overall survival and event-free survival with events defined by biochemical recurrence, secondary treatment, prostate cancer metastasis, and death. We were unable to demonstrate a difference between baseline serum testosterone level measured as a continuous variable, as quartiles, or as a dichotomous variable (above/below 150 ng/dl) with the outcomes measured. This finding was observed in both arms of the study. Baseline serum testosterone level did not predict outcomes in men with clinically localized high-risk prostate cancer treated with radical prostatectomy alone or neoadjuvant chemohormonal therapy and radical prostatectomy.

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

Biology-guided radiation therapy (BgRT) guides radiation therapy in real time based on positron emissions detected during treatment delivery. Protein specific membrane antigen (PSMA) is a positron emission tomography (PET) tracer with superior sensitivity and specificity for prostate cancer detection compared with conventional imaging. This study aims to quantify the ratio of standard uptake value (SUV) to background SUV for patients with low volume prostate cancer metastases, in the context of determining suitability of these lesions for BgRT. A single institutional patient subset from the ProPSMA prospective clinical trial underwent Ga-68-PSMA-11 at the time of prostate cancer diagnosis with suspected localized disease. From this cohort of 84 patients, 15 had at least one metastatic site disease diagnosed, 1 to 11 lesions per patient, with a total of 43 metastatic lesions (12 bones/31 viscerals). Metastatic gross tumor volume (GTV) were delineated on PSMA-PET images by using a patient-specific fixed SUV threshold method. In order to determine the suitability of various BgRT tracking zones, 3D shells of thickness 5 mm, 10 mm and 20 mm were constructed around the GTV to represent adjacent non-tumor background. Normalized SUV (nSUV) was calculated as the ratio of SUVmax in the GTV to SUVmean of adjacent shell. Sensitivity of nSUV to shell thickness variation was reported as the difference between nSUV values obtained for each thickness. GTV SUVmax ranged from 2.9 to 48.0 (median, 12.0; IQR, 5.1 to 19.5). nSUV ranged from 2.4 to 42.6 for 5 mm shell, 2.7 to 47.5 for 10 mm shell and 2.6 to 36.4 for 20 mm shell. Bone metastases had increased SUVmax compared with visceral metastases (SUVmax min/median/max 2.9/15.0/48.0 for bone compared with 2.9/11.0/40.0 for visceral). Furthermore, 90% of lesions had nSUV greater than 2.9 for a shell thickness of 5 mm, 3.1 for a shell thickness of 10 mm, and 3.2 for a shell thickness of 20 mm. Moreover, 100%/93%/84% of lesions would be suitable for BgRT by using nSUV cut-off of 2/3/4 and a shell thickness of 10 mm. nSUV decreased with increasing shell thickness for 17 lesions, indicating high signal in adjacent non-tumor tissue due to the proximity of bladder (5), bowel (4), other lesion (4), vessel (3) and liver (1). This study demonstrates that it is feasible to identify metabolically defined radiotherapy targets in the setting of BgRT. High lesion to background signal was observed for metastases visible on Ga-PSMA-EPT-11, however a subset of metastases had adjacent non-tumor uptake which may require exclusion from emission tracking during BgRT. Trial ID ACTRN12617000005358.

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.

Evaluation of the efficacy and safety of cabazitaxel in combination with prednisone in patients with metastatic castration-resistant prostate cancer who have previously received docetaxel chemotherapy in daily clinical practice. Results of a Russian multicenter prospective study

Materials and methods. From September 19, 2016 to December 27, 2019, 104 patients received cabazitaxel plus prednisone for a maximum of 10 cycles or disease progression, or unacceptable toxicity, or patient request to stop treatment. Adverse events occurring during treatment, including use of granulocytic colony stimulating factors, were collected. Prostate specific antigen response, objective tumor response (RECIST), progression-free survival and overall survival were analyzed. Treatment period was followed by a follow-up period of 82.0 (36.0–117.0) weeks. Results. 104 patients with histologically proven adenocarcinoma were enrolled and treated. All were Caucasian with a median age of 66 (range 46.0–86.0) years and a median BMI-Score of 26.8 (18.7–43.3) kg/m2. Most patients (57/104, 54.8 %) were ECOG 1. At the time of prostate cancer diagnosis, 63/104 (60.6 %) patients had metastatic disease. The median duration of therapy was 14.5 (0.1–39.0) weeks and the median number of cycles cabazitaxel was 5; 30 (28.8 %) patients received 10 cycles of treatment. Granulocytic colony stimulating factors was received by 52 (50.0 %) patients (prophylactic, n = 31; curative, n = 21). Overall, 102/104 (98.08 %) patients reported at least one treatment emergent adverse event (TEAE), 21/104 (20.19 %) grade ³III TEAEs and 12/104 (11.54 %) serious adverse events. Most TEAEs resolved but 9/104 patients discontinued treatment due to TEAE. Most common TEAEs were related to gastrointestinal system disorders (46/104 (44.23 %) patients, mainly nausea n = 40); blood and lymphatic system disorders (44 (42.31 %) patients, mainly leukopenia n = 22, anemia n = 15, neutropenia n = 11) and general disorders/administration site conditions (22 (21.15 %) patients; mainly asthenia n = 21). Main grade ³III adverse events were related to blood and lymphatic system disorders (11 (10.58 %), including one case of febrile neutropenia), general disorders/administration site conditions (6 (5.77 %), mainly asthenia) and cardiac disorders in 2 (1.92 %) patients. A prostate specific antigen decline of at least 50 % was observed in 23 out of 31 patients with evaluable prostate specific antigen measurements. The objective tumor response was observed in 29 (27.9 %) patients, including 7 (6,7 %) with complete response and 22 (21.2 %) with partial response. Treatment was completed as initially planned in 41/104 (39.4 %) patients, and 61/104 (58.7 %) reached the last follow-up visit. At the last follow-up visit, median overall survival was not reached due to a low number of events. Median progression-free survival at the end of treatment visit was 6.29 (5.1–10.45) months and reached 10.13 (5.55–19.27) months at the last follow-up visit. There was no reported death related to treatment of cabazitaxel during the period of treatment and follow-up period. Conclusion. This prospective, multi-center, national observational, non-interventional register conducted in patients with mCRPC in Russian Federation suggests that cabazitaxel is effective with a manageable safety profile.

Patient-reported outcome measures after treatment for prostate cancer: Results from the Danish Prostate Cancer Registry (DAPROCAdata)

PurposeThis study compares the side effects of active surveillance, prostatectomy, radiation with or without adjuvant endocrine therapy, watchful waiting, and palliative therapy on patient-reported outcomes in a nationwide, population-based cohort of Danish men with prostate cancer. MethodsA total of 15,465 participants completed questionnaires over a 5 year period (2011–2016). Condition-specific quality of life, focusing on urinary function, bowel incontinence, sexual function, and hormonal symptoms were investigated using the validated EPIC-26 questionnaire at diagnosis, 1 year- and 3- year follow-up. Patients were identified from the Danish Prostate Cancer Registry with data-linked to several national healthcare registries. Longitudinal analysis with linear mixed effects models were fitted to compare changes over time on quality of life symptom scores for five treatment modalities, adjusting for age, clinical TNM stage, PSA value, Gleason score, Charlson Comorbidity score, education, disposable income, and urbanization measured at time of prostate cancer diagnosis. ResultsThere was a more than10-point decrease in mean scores across all symptom domains at 1-year follow-up. Thereafter mean scores for all symptom domains improved marginally and remained relatively unchanged at 3-year follow-up. Prostatectomy had the greatest negative effect on sexual function and urinary incontinence. Overall quality of life was most adversely affected by sexual function, regardless of treatment modality. ConclusionClinical interventions for improving symptoms should focus particularly on the first year after prostate cancer diagnosis. Greater emphasis on improving sexual function should be practiced in clinical and rehabilitative care, since this area has the single greatest impact on symptom-specific QoL after primary treatment for prostate cancer.

Prise en charge du cancer de la prostate oligo-métastatique

To review biology and management of oligometastatic prostate cancer. Relevant publications were identified through Medline (www. ncbi.nlm.nih.gov), Embase (www.embase.com) and the US National Library of Medicine (www.clinicaltrials.org) databases using the following keywords, alone or in association, «prostate cancer; metastasis; oligo-metastasis». Articles were selected according to methods, language of publication and relevance. After careful selection 99 publications were eligible for our review. Oligometastatic prostate cancer is a new entity including prostate cancer with a limited number of metastasis. This particular state becomes more frequent with the imaging progresses especially with the common use of new PET imaging with Choline or PSMA. There is no consensus about a strict definition of oligometastatic prostate cancer, number and sites of metastasis vary widely in the literature. Moreover, oligometastatic state can be observed de novo at the time of prostate cancer diagnosis as well as in case of recurrence after a primary treatment. There is actually an important lack of evidence-based medicine and no guidelines regarding treatment can be found. In de novo oligo-metatastatic prostate cancer, treatment of the primary tumor in association with androgen deprivation therapy seems to increase survival in selected patients but this needs to be confirmed by ongoing prospective clinical trials. In recurrent prostate cancer, metastasis directed therapy with or without androgen deprivation therapy is now routinely performed but its impact needs also to be analyzed. In absence of consensus or guidelines, management of prostate cancer should be an individualized, patient-based management taking into account primary tumor stage and grade, number and types of metastasis and patient characteristics.

839P - Clinico-genomic profiling and outcome prediction of neuroendocrine prostate cancer (NEPC)

Background: NEPC is a variant of prostate cancer that may present “de novo” or after androgen receptor (AR)-targeted therapies (“treatment related”) with a spectrum spanning both small cell prostate cancer (SCPC) and adenocarcinoma with neuroendocrine differentiation (adeno-NE). The comprehensive clinical and molecular landscape of different NEPC subtypes and its potential impact on outcome is poorly understood. Methods: 274 prostate cancer patients (pts) with metastatic biopsy tumor morphology confirming NEPC (n = 97; 36 with SCPC and 51 with adeno-NE) or castration resistant adenocarcinoma (CRPC) (n = 187) between 2004 and 2017 in a single academic center were evaluated. Baseline, treatment and outcomes data along with tumor whole-exome and RNA-seq data were retrospectively reviewed. Statistical comparisons utilized Cox regression analysis and Kaplan-Meier method for association with NEPC, CRPC and overall/progression-free survival (OS/PFS). Results: In NEPC, PSA at time of biopsy was lower compared with CRPC (median 1.18 vs 38.0, p = 0.001) and liver metastases were more common (32.2% vs 52.1%, p = 0.027). OS from time of prostate cancer diagnosis differed by subtype, with SCPC having shortest survival (median 2.98 years), followed by adeno-NE (median 5.98 years) then CRPC (median 12.14 years) (log rank p < 0.0001), with similar results seen with time from metastases (log rank p < 0.0001). AR alterations were more frequent in CRPC (p < 0.001), while RB1 (p = 0.001) and TP53 (p = 0.048) alterations and high NEPC mRNA score (p = 0.007) were more common in NEPC. For CRPC pts treated with abiraterone or enzalutamide, shorter PFS was observed when somatic alterations in RB1 (p = 0.067) or TP53 (p < 0.0001) were present. Elevated NEPC score (p = 0.006), serum CGA above upper limit of normal (p = 0.033), and presence of liver metastases (p < 0.001) were prognostic for time to death from diagnosis among pts with CRPC. Conclusions: NEPC is associated with lower PSA, higher frequency of liver metastases, and worse prognosis compared with CRPC, with SCPC having the shortest OS. The presence of NEPC clinical or molecular features in CRPC is also prognostic. Further studies of this aggressive form of prostate cancer are warranted. Legal entity responsible for the study: Weill Cornell Medicine. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.