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Background: Prostate cancer (PC) rarely metastasizes to the central nervous system (CNS). In this retrospective single-institution study at a tertiary cancer center, we aimed to evaluate the clinical and genetic characteristics of advanced PC patients with CNS metastases., Patients and Methods: Between January 2010 and March 2020, 12 out of 579 patients with extracranial metastatic PC were identified to have CNS metastases based on imaging, including six patients with brain metastases (BMs), five patients with dural metastases, and one unknown. These patients were followed up through March 2022. Clinical data were compared to the overall cohort of patients evaluated at our cancer center during that decade. Genetics information was also analyzed for the patients with available data via cell-free DNA (cfDNA) blood samples., Results: Median time from development of extracranial metastatic disease to development of CNS metastases was 5.5 years (95% CI, 1.8-7.0). Median overall survival (mOS) from diagnosis of CNS metastases was 6.1 months (95% CI, 5.8-8.2). Notably, there was no significant difference in mOS after development of extracranial metastases in patients with CNS metastases (6.4 years; 95% CI, 4.6-7.9) compared to the patients without known CNS metastases (5.2 years; 95% CI, 4.6-5.7) (P = .91). For the cohort with CNS metastases, nine patients had germline testing and seven patients had somatic testing via cfDNA., Conclusion: PC patients with CNS metastases did not often die from a neurological cause. With advancing therapies, the overall prognosis of metastatic PC continues to improve, and CNS metastases will become more common., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Clinical trials have demonstrated the efficacy of several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC); however, real-world data on their use, survival effect, and safety are limited. Using electronic health record data from the Flatiron Health database, we studied real-world treatment patterns and health outcomes in patients with mCRPC., Patients and Methods: We conducted a retrospective, non-interventional cohort analysis of electronic health record data of patients with confirmed mCRPC between January 2013 and September 2017. The primary objective was to describe real-world treatment patterns, including treatment type, duration, and sequencing. Secondary objectives included describing patient characteristics and clinical outcomes., Results: Of 2559 patients with mCRPC, 1980 (77%) received at least 1 line of life-prolonging therapy (abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, or radium-223). Of patients receiving first-line therapy, 49% received second-line therapy, and of these, 43% received third-line therapy. Abiraterone/prednisone and enzalutamide accounted for 65% of first-line therapies and 54% of second-line therapies. Docetaxel was the most common third-line therapy (24%). Back-to-back use of abiraterone/prednisone and enzalutamide was common. Radium-223 monotherapy use was 2% in the first-line setting, 3% in the second-line setting, and 8% in the third-line setting. The median overall survival was longer in patients who received life-prolonging therapies (23.7 months; 95% confidence interval: 22.3-25.1 months) than in those who did not (10.1 months; 95% confidence interval: 9.1-11.5 months)., Conclusion: These real-world insights on over 2500 patients with mCRPC supplement findings from randomized controlled trials and may help to inform clinical trial design, treatment guidelines, and clinical decision-making., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Circulating tumor DNA (ctDNA), which can be assessed by liquid biopsy, can provide valuable genomic information that may affect treatment response in prostate cancer. The aim of this study was to characterize TP53 mutations and treatment history in prostate cancer., Patients and Methods: This study included 143 patients with metastatic castration-resistant prostate cancer who had undergone ctDNA sequencing via Guardant360 testing. The presence or absence of TP53 mutations was analyzed along with treatment history for this group. TP53 mutations were further classified as gain of function (GOF) or not GOF, and analyzed with prior therapies., Results: Chi-square analysis was performed for treatment history and TP53 status (further specified as all TP53 mutations or only TP53 GOF mutations). There were no associations between prior receipt of abiraterone/enzalutamide therapy and all TP53 mutations, or between docetaxel therapy and all TP53 mutations. However, TP53 GOF mutations had a positive association with prior abiraterone/enzalutamide therapy (P = .047). There was no association of TP53 GOF mutations with prior docetaxel therapy. The most frequent alterations co-occurring with all TP53 mutations were in AR, BRAF, EGFR, MYC, and PIK3CA. Common coalterations with TP53 GOF mutations included AR, BRAF, EGFR, RB1, NF1, and PIK3CA. There was an association of RB1 mutations with TP53 GOF mutations, versus RB1 mutations and no TP53 GOF mutations (P = .0036)., Conclusion: TP53 GOF mutations may provide a valuable pathway to delineate metastatic castration-resistant prostate cancer TP53 mutations into therapeutic categories. Association with disease progression while receiving abiraterone/enzalutamide therapy was apparent in this study; however, further studies are needed to elaborate the therapeutic and prognostic implications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Previous studies have reported conflicting results on the relationship between androgen deprivation therapy (ADT) and the risk of depression. We assessed whether ADT is associated with depression in a unique data set of men with recurrent prostate cancer., Patients and Methods: We studied a cohort of 656 men in the prospective COMPARE (Comprehensive, Multicenter, Prostate Adenocarcinoma) registry who experienced biochemical recurrence after radiation therapy (RT) only, radical prostatectomy (RP) with or without RT, or ADT with RP or RT. Multivariable logistic regression was used to determine the relationship between the modality of treatment and patient-reported depression., Results: Of 656 men, 44 (6.7%) experienced depression. The prevalence of depression stratified by treatment was 3.2% for RT only, 5.9% for RP with or without RT, and 9.1% for ADT plus RP or RT. Compared with RT-only, ADT plus RP or RT was associated with a significantly increased rate of depression (P = .031) and RP with or without RT was not (P = .195). On multivariate analysis adjusting for age and baseline comorbidities, the receipt of ADT was associated with an increased risk of depression (odds ratio, 3.29; 95% confidence interval, 1.11-9.76; P = .032) compared with RT only. No statistically significant difference was found in the risk of depression for men who received RP with or without RT versus RT only (odds ratio, 2.12; 95% confidence interval, 0.68-6.65; P = .19)., Conclusion: Men with recurrent prostate cancer who underwent ADT were 3 times more likely to report experiencing depression. Treating physicians should discuss depression as a possible side effect when considering the use of ADT and should screen for depression in men who have received ADT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Radium-223 has shown clinical efficacy in metastatic castration-resistant prostate cancer. Despite improvement in quality of life and survival, practice patterns and utility of this agent outside the context of clinical trials have not been fully characterized. The primary objective in this study was to evaluate variables associated with completion of 5 to 6 radium-223 doses., Patients and Methods: We conducted retrospective analyses of patients who received radium-223 (n = 135). Patients were classified into 3 cohorts: 1 to 2, 3 to 4, or 5 to 6 radium-223 doses. We evaluated the association of clinical and laboratory variables with the number of cycles administered (5-6 vs. 1-4 doses)., Results: Twenty-five patients (18.5%) received 1 to 2 radium-223 doses, 27 (20.0%) received 3 to 4, and 83 (61.5%) received 5 to 6. The most common reasons for treatment discontinuation included disease progression (61.5%, n = 40), patient preference (15.4%, n = 10), and toxicity (10.8%, n = 7). Factors associated with therapy completion in univariate analysis included previous sipuleucel-T treatment (P = .068), no previous abiraterone or enzalutamide treatment (P = .007), hemoglobin ≥ lower limit of normal (LLN; P = .006), white blood cell count ≥ LLN (P = .045), absolute neutrophil count (ANC) ≥ LLN (P = .049), lower alkaline phosphatase (P = .029), and lower lactate dehydrogenase levels (P = .014). Factors associated with therapy completion in multivariable analysis included previous sipuleucel-T treatment (P = .009), hemoglobin ≥ LLN (P = .037), and ANC ≥ LLN (P = .029)., Conclusion: Several clinical parameters are associated with radium-223 therapy completion. In general, these parameters reflect earlier disease stage. These data are hypothesis-generating and prospective testing of the optimal number of radium-223 doses is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity., Patients and Methods: Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients., Results: Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] = 2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P = .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia. Neutropenia events were too few in placebo patients for a comparative analysis. There were no significant associations between hematologic toxicities and number of radium-223 injections received (4-6 vs. 1-3)., Conclusion: Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ratio of the second to the fourth digits (2D:4D) has been linked to prenatal androgen exposure and prostate cancer (PCa). The use of alternative finger ratios has been shown to be a greater indicator of sexual dimorphism when compared with the traditional 2D:4D ratio. This study aimed to assess the relationship between alternative digit ratios, racial demographics, and clinical/pathologic parameters associated with PCa., Materials and Methods: Digital finger length measurements were made from scanned images of hands from patients with PCa. Race, age, family history, history of metastasis, and Gleason score at diagnosis were assessed in a cross-sectional clinic-based study. Demographic and clinical parameters were analyzed with respect to various alternative finger length ratios., Results: Hand measurements were obtained in 354 white and 98 African-American patients with PCa. African-American men were more likely to have a smaller 2D:3D (P < .0001) and 2D:4D digit ratio (P < .0001) in both hands. Larger right (R)3D:5D (P = .0005), R4D:5D (P = .0014), and R2T:2D (P = .0501) digit ratios were present in African-Americans compared with whites. In exploratory analyses, African-American men with a smaller left (L)2T:2D ratio were younger at the time of PCa diagnosis (P = .0125). No relationship was found between the various digit ratios and Gleason score, the presence of metastatic disease, or family history., Conclusion: Various alternative finger length ratios show strong differences between African-American and white men in this study. The potential relationship between the 2T:2D ratio and age at diagnosis in African-Americans needs additional verification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders., (Published by Elsevier Inc.)

Background: Careful descriptions of men with prostate cancer (PCa)-specific mortality are scant in nontrial settings. The present retrospective review describes the clinical characteristics, timelines, and treatment histories from initial presentation to death in a cohort of men with metastatic, castrate-resistant PCa (mCRPC). Unique to the present study is the unequivocal attribution of PCa death by a single experienced clinician., Patients and Methods: A total of 119 patients who had been treated at Tulane Cancer Center and had died of mCRPC from 2008 to 2015 were studied through a retrospective review of the medical records., Results: The median age at diagnosis was 65 years (range, 40-85 years), and 34.4% of the patients presented with metastatic disease (stage M1). Of these patients, 56% had received definitive primary therapy, all had received androgen-deprivation therapy, and 52% had received docetaxel. The patients had received a median of 7 (1-14) systemic therapies before death. Most were secondary hormonal manipulations after the diagnosis of mCRPC (median, 4; range, 0-9). The median survival was 69 months (range, 5-270 months) after diagnosis, and the median age at death was 73 years (range, 47-95 years). The presence of metastases at diagnosis was a significant predictor of early death (hazard ratio, 4.33; P < .001), and definitive primary therapy was a significant predictor of longer survival (P < .001). The median survival for patients presenting with metastases was 39 months (range, 5-235 months) compared with 100 months (range, 6-270 months) for those with localized disease (P < .001). The median age at diagnosis between the docetaxel- and non-docetaxel-treated patients was significantly different at 62 and 71 years, respectively (P = .002)., Conclusion: The present retrospective analysis provides initial views clarifying the clinical characteristics of men dying of mCRPC and the therapies they received before death. Additional data are needed in multi-institutional settings to confirm these findings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: We hypothesized that the adverse event (AE) profile of cabazitaxel with regard to alopecia, nail changes, neuropathy, and dysgeusia differs from docetaxel., Materials and Methods: Prospectively collected data on treatment-emergent AEs (frequency and grade [G]) from clinical trial databases of docetaxel every 3 weeks (q3w) (in TAX327 and VENICE) and cabazitaxel q3w (in TROPIC) were analyzed., Results: The frequency of new or worsening AEs (all G and G3-4) for 1301 patients was significantly less for alopecia, nail changes, neuropathy, and dysgeusia for cabazitaxel compared with docetaxel., Conclusion: Treatment with cabazitaxel might cause less alopecia, nail changes, neuropathy, and dysgeusia compared with docetaxel., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: This study aimed to examine the impact of advanced prostate cancer and its treatments on patients' perceptions of their health and to better understand concerns not captured by currently available health-related quality of life (HRQL) instruments., Patients and Methods: Open ended one-on-one interviews were conducted with patients with prostate cancer who had biochemical failure or metastatic cancer to understand the impacts of disease and treatments on patients' perceptions of their lives. Interviews with 25 patients (7 biochemical failure and 18 metastatic) and 6 clinicians were conducted. Patient responses were analyzed to assess whether information saturation (ie, the point at which no new information is collected) was attained and compared with currently available HRQL instruments. The data informed the development of a comprehensive conceptual model illustrating the impacts of advanced disease and treatments. Clinical expert interviews also informed the conceptual model., Results: Patients with prostate cancer reported many of the key symptoms already captured by current measures, such as bone pain, urinary functioning, bowel functioning, and fatigue. However, a number of impacts reported as bothersome by patients were identified that are not fully captured by existing HRQL measures. Specific examples include genital atrophy, muscle atrophy, stamina, body image, and emotional well-being., Conclusion: The conceptual model identified herein describes the impacts of prostate cancer and its treatments from the patient's perspective. The model can be useful in identifying key concepts important to patients that should be measured in trials to capture treatment benefits. The model also can help inform the selection of patient-reported outcomes to assess these benefits., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Recent American Urologic Association Guidelines for small renal masses recommend partial nephrectomy for surgical treatment of T1 renal masses to preserve renal function and minimize cardiovascular comorbidities. This procedure is performed more often than in the past, after the technical issues of hemorrhage, fistula, and technique evolved. We reviewed the trends, practice patterns, and application of partial nephrectomy for T1 renal cell carcinoma in the United States from 2000 to 2008, before the American Urologic Association Guidelines. The objective is to investigate whether economic or societal factors favor the use of partial over radical nephrectomy surgery., Methods: Data on 142,194 cases from 1267 hospitals diagnosed with kidney and renal pelvis cancer in the National Cancer DataBase from 2000 to 2008 were the basis of the study., Results: Partial nephrectomy rates for stage T1 kidney and renal pelvis cancer have increased from 17% in 2000 to 31% in 2008. Differences in partial nephrectomy rates that arise from sex or race were not large. However, there was a disproportionate increase based on income and education. Also, there were differences based on insurance status; patients with managed care, in the military and veterans had higher partial nephrectomy rates. Partial nephrectomy rates were higher in teaching and research hospitals and in veterans hospitals. Geographically, the procedure was performed at higher rates in the eastern and midwestern parts of the country., Conclusions: Partial nephrectomy rates for stage T1 renal cell carcinoma increased from 17% in 2000 to 31% in 2008. The procedure has been used preferentially with patients who are more educated and have high incomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The FDA's approval of docetaxel in 2004 created a clear mandate for clinical researchers to create new therapies effective for metastatic castrate-resistant prostate cancer (mCRPC) patients with progression post-docetaxel. In 2010, the first trial to prolong survival in this setting was announced using a cabazitaxel, a novel taxane. This therapeutic agent was specifically designed to have activity in model systems resistant to conventional taxanes. After phase I testing, with observation of clinically significant activity in patients with advanced cancers, cabazitaxel/prednisone was tested in a large phase III trial enrolling patients with mCRPC who had disease progression despite prior docetaxel therapy. This phase III trial TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated With a Taxotere-Containing Regimen), using mitoxantrone/prednisone as a control arm, demonstrated a significant improvement in survival (the primary endpoint). Both subset analyses and secondary endpoints (response rates and time to progression) were supportive of the survival findings. This trial was pivotal for the FDA's approval of the new drug application for cabazitaxel. This review focuses on both the pre-clinical and clinical development of cabazitaxel.

Background: Ketoconazole is a commonly used secondary hormonal therapy in castration-refractory prostate cancer (CRPC), but disease progression inevitably occurs. Both prostatic and metastatic lesions in patients with CRPC overexpress 5-alpha reductase (SRDA5) type I. We hypothesized that SRDA5 inhibition in combination with ketoconazole would mitigate progression after treatment with ketoconazole alone., Patients and Methods: A total of 10 patients with CRPC with progression after ketoconazole treatment were treated with a combination of ketoconazole plus dutasteride 0.5 mg/day, a dual SRDA5 inhibitor., Results: After dutasteride addition, 8 (80%) of the 10 patients had varying degrees of prostate-specific antigen (PSA) decline relative to baseline. Median progression-free survival after dutasteride addition was 4.9 months (range, 2.7+ to 9.8 months); no patient had a >OR= 50% PSA decline., Conclusion: We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC.

Prostate cancer is the most commonly diagnosed malignancy among American men. Although prostate cancer-related death approximates only 3%, advanced disease can become widely disseminated. Metastatic disease is often found in a number of common sites. We report the uncommon presentation of a solitary adrenal lesion treated with surgical resection.

Purpose: The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (153Sm- EDTMP) were investigated in men with hormone-naive prostate cancer metastatic to bone., Patients and Methods: Within 30 days of initiating androgen deprivation, the first of 4 planned doses of 153Sm- EDTMP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received 153Sm-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses., Results: There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received 153Sm-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of 153Sm-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of 153Sm-EDTMP. There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities., Conclusion: In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repeated doses of 153Sm-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses.

In this study, we provide consensus guidelines for the use of bisphosphonates in men with prostate cancer. To this end, an expert panel composed of urologists, medical oncologists, radiation oncologists, and endocrinologists met to review current clinical evidence for the use of bisphosphonates in patients with different stages of prostate cancer to derive consensus recommendations. Physicians should be proactive in monitoring bone loss in patients receiving long-term androgen-deprivation therapy for prostate cancer. Further study is needed before recommending the routine use of bisphosphonates in men with nonmetastatic prostate cancer. However, if a patient has clinically significant bone loss, use of a bisphosphonate to prevent further compromise of bone integrity should be strongly considered, regardless of hormonal and metastatic status. Bone scans are the preferred method for the identification of bone metastases. In patients with hormone-refractory prostate cancer and bone metastases, zoledronic acid is the only bisphosphonate indicated for the prevention of skeletal complications. In conclusion, patients with prostate cancer are at high risk for skeletal morbidity. Bisphosphonates have been shown to prevent cancer treatment-induced bone loss in men receiving androgen-deprivation therapy as well as skeletal complications in men with bone metastases. However, further study of the use of bisphosphonates across the clinical spectrum of prostate cancer is needed.