Racial Disparities in Prostate Cancer–Specific Mortality in Men With Low-Risk Prostate Cancer

BackgroundMen with low-risk prostate cancer (CaP) are considered unlikely to die of CaP and have the option of active surveillance. This study evaluated whether African American (AA) men who present with low-risk disease are at higher risk for death from CaP than white men.Patients and MethodsThe authors identified 56,045 men with low-risk CaP (T1-T2a, Gleason score ≤ 6, prostate-specific antigen ≤ 10 ng/mL) diagnosed between 2004 and 2009 using the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing-risks regression analyses were used to analyze the effect of race on prostate cancer–specific mortality (PCSM) after adjusting for known prognostic and sociodemographic factors in 51,315 men (43,792 white; 7523 AA) with clinical follow-up information available.ResultsAfter a median follow-up of 46 months, 258 patients (209 [0.48%] white and 49 [0.65%] AA men) died from CaP. Both AA race (adjusted hazard ratio [AHR], 1.45; 95% CI, 1.03-2.05; P = .032) and noncurative management (AHR, 1.49; 95% CI, 1.15-1.95; P = .003) were significantly associated with an increased risk of PCSM. When analyzing only patients who underwent curative treatment, AA race (AHR, 1.62; 95% CI, 1.04-2.53; P = .034) remained significantly associated with increased PCSM.ConclusionAmong men with low-risk prostate cancer, AA race compared with white race was associated with a higher risk of PCSM, raising the possibility that clinicians may need to exercise caution when recommending active surveillance for AA men with low-risk disease. Further studies are needed to ultimately determine whether guidelines for active surveillance should take race into account.     

Is There a Flare Phenomenon on Bone Scintigraphy in Men With Advanced Prostate Cancer Treated With Radium-223?

Introduction

Radium-223 is an approved survival-prolonging treatment option in men with castration-resistant prostate cancer (mCRPC) and bone metastases. In the registration trial (ALSYMPCA), no regular imaging was mandated. We aimed to analyze men with metastatic mCRPC treated with radium-223 who had bone scintigraphy for staging and treatment monitoring.

Elective Pelvic Nodal Irradiation With a Simultaneous Hypofractionated Integrated Prostate Boost for Localised Prostate Cancer: Ready for Prime Time?

External beam radiotherapy is a standard treatment option for localised prostate cancer and hypofractionation has become an alternative to conventionally fractionated radiotherapy. In patients who receive external beam radiotherapy, elective pelvic nodal irradiation is sometimes delivered, especially in patients with unfavourable disease who are at risk of micrometastatic spread of cancer into the regional nodes. One elegant approach to combine prostate hypofractionation with elective pelvic nodal irradiation is with a simultaneous integrated boost technique, where a radical hypofractionated dose is delivered to the prostate while the regional pelvic nodes receive a lower microscopic dose simultaneously in a single radiotherapy plan over the same number of treatment fractions. This article reviews the existing published literature evaluating such an approach.     

Living With Cancer Alone? The Experiences of Singles Diagnosed With Colorectal Cancer

This paper seeks to understand the experiences of single colorectal cancer patients. This study consisted of 12 semi-structured interviews that were digitally voice-recorded, transcribed, and analyzed. Six main themes emerged: (a) gradual shift in view of cancer diagnosis from fatalistic to normalized, (b) perception of cancer as a nadir experience, (c) concerns of singlehood, (d) factors influencing cancer experiences, (e) factors influencing coping with cancer, and (f) range of responses towards cancer diagnosis. Singles with colorectal cancer require short- to long-term individualized care plans, and psycho-emotional support. This may help enhance their individual coping and adjustment to the diagnosis.     

Low-Dose Enzalutamide in Late-Elderly Patients (≥ 75 Years Old) Presenting With Metastatic Castration-Resistant Prostate Cancer

BackgroundEnzalutamide, a major antiandrogen indicated for metastatic castration-resistant prostate cancer, has worrisome toxicities in aging patients. Dose reduction might limit toxicity, but potential loss of efficacy is a concern. We compare up-front low-dose versus standard-dose enzalutamide.Patients and MethodsRecords of prostate cancer patients receiving enzalutamide were retrospectively retrieved. Selection criteria were: age ≥ 75, metastatic disease, surgical or medical castration, and rising prostate-specific antigen (PSA). Data were excluded of those missing follow-up PSA values. Low-dose enzalutamide (≤ 80 mg per day) was compared to standard dose (160 mg per day). Progression-free survival analyzed the time from start of enzalutamide to event, defined as ≥ 25% and ≥ 2 ng/mL PSA increase above nadir, or death from any cause.ResultsFifty-nine patients were identified, of whom 16 received low-dose and 43 standard-dose therapy. Patients in the low-dose group were significantly old, with a median (range) age of 84.6 (74.9-93.8) years; median (range) PSA at start of enzalutamide was 59.2 (11.0-1058.3) ng/mL; 11 had bone metastases only, 2 metastatic lymph nodes only, and 3 bone and lymph node localizations. Pain score was > 3/10 in 4 patients (27%), Eastern Cooperative Oncology Group performance status was ≥ 2 in 9 (56%); 3 patients had received prior abiraterone and 3 bicalutamide. None received chemotherapy. PSA decrease of ≥ 50% at 12 weeks was observed in 67% patients (10/15), versus 45.0% with standard dose. Median (range) PSA at last follow-up was 1.6 (0-599.3) ng/mL. Median progression-free survival was 11.2 months, versus 11.9 months for patients receiving the standard dose (P = .612).ConclusionLow-dose enzalutamide in very old, symptomatic, poor-performance patients with metastatic disease was associated with high response rate and survival comparable to standard dose.     

What Do Prostate Cancer Patients Die Of?

Background.

A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death.

Methods.

Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death.

Findings.

Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16–1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09–1.37), and heart failure (HR, 1.18; 95% CI, 1.11–1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14–2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55–1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84–1.96).

Interpretations.

Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.     

New Hormonal Agents in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: Meta-Analysis of Efficacy and Safety Outcomes

In the past few years several hormonal agents have been tested in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) leading to an impressive improvement in terms of metastases-free survival (MFS). We performed a meta-analysis aimed to: (1) estimate the pooled effect of new hormonal compounds in terms of MFS, overall survival (OS) in overall and specific subpopulations; and (2) estimate the effect of high-grade toxicities of these drugs. We identified 881 studies published between January 1, 2010 and February 16, 2018 on PubMed/Medline, Cochrane Library, and Scopus. Three randomized placebo controlled clinical trials were selected (PROSPER, SPARTAN, and ARAMIS). Because of the absence of individual data, all of the analyses performed were made on aggregated data provided in selected studies. We used the inverse variance technique for the meta-analysis of the hazard ratios collected for MFS and OS analysis. Fixed and randomized models were used. Relative risk and 95% confidence intervals and risk difference were estimated considering the number of Grade 3 adverse events in treatment and control arms. Administration of new hormonal compounds in nmCRPC patients led to a significant benefit in MFS in the overall population and in all subgroups analyzed. These agents might also improve OS but longer follow-up is needed to confirm this hypothesis. Indeed results of OS analysis should be carefully evaluated because none of the studies selected provided mature OS data. Administration of these agents resulted in a significant increased risk of treatment-related death, high cardiovascular toxicity, hypertension, fractures, and falls. Administration of new hormonal compounds prolongs the time of metastases occurrence and might prolong also survival in patients with nmCRPC. Treatment-related toxicity is an important issue because these agents increase the risk of death, cardiovascular toxicity, hypertension, fractures, and risk of falls.     

Red Cell Distribution Width Predicts Prostate-Specific Antigen Response and Survival of Patients With Castration-Resistant Prostate Cancer Treated With Androgen Receptor Axis–Targeted Agents

PurposeTo identify the impact of red cell distribution width (RDW) on treatment outcomes in patients with castration-resistant prostate cancer (CRPC) treated with androgen receptor axis–targeted agents (ARATs).Patients and MethodsBaseline data were obtained from 153 patients with CRPC treated with ARATs. Patients were stratified according to the upper limit of the normal RDW range, measured within 1 month before starting treatment. Relationships between RDW levels and the best prostate-specific antigen (PSA) response, PSA progression-free survival, and overall survival were examined.ResultsForty-nine patients were treated with abiraterone acetate in combination with corticosteroid and 104 with enzalutamide. The median RDW was 13.7% (interquartile range, 13.0?14.9). High RDW was significantly associated with prior use of docetaxel (P < .001), presence of lymph node metastasis (P = .031), presence of visceral metastasis (P = .001), and low hemoglobin (P < .001), low albumin (P = .016), and high C-reactive protein levels (P = .02). In a multiple linear regression model, there was a statistically significant negative association between RDW levels and the best PSA response (P = .046). In addition, multivariate Cox regression analyses showed that high RDW was an independent predictor of both shorter PSA progression-free survival (hazard ratio = 1.84; 95% confidence interval, 1.04-3.27; P = .037) and overall survival (hazard ratio = 2.62; 95% confidence interval, 1.15-5.98; P = .022), showing statistical significance.ConclusionHigh RDW is an independent predictor of worse treatment outcomes in patients with CRPC treated with ARATs. RDW could be a readily available and inexpensive biomarker for predicting primary resistance to ARATs.     

Sublethal Irradiation Promotes Migration and Invasiveness of Prostate Cancer PC-3 Cells：Implications for Radiotherapy of Human Prostate Cancer

OBJECTIVE To study the changes in the matrix metalloproteinases-2 and 9 （MMP2, MMP9） induced by ^60Co γ-ray external irradiation of human prostate cancer PC-3 cells. METHODS Human prostate cancer PC-3 cells were irradiated with different doses of ^60Co γ-rays. Cell migration and invasiveness were evaluated and the expression of MMP2, and MMP9 was investigated by RT-PCR, Western blotting and flow cytometry（FCM）. RESULTS Irradiation enchances invasive protential at the doses of 1,3 and 5 Gy,whereas it significantly inhibits cell migration. CONCLUSION The different doses of ^60Co γ-ray external irradiation for prostate cancer may have different effects through the changes of MMP2, and MMP9 expression.     

Immunotherapy for Prostate Cancer: What's the Future?

Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer death among US men. A greater understanding of basic immunologic principles has led to a variety of new techniques,which has led to advancements in prostate cancer vaccines. This article discusses the rationale for the development of antibody-based therapy and vaccines therapy, including whole tumor cells, dendritic cells, and pox viral vectors. A summary of selected clinical studies incorporating these strategies and new approaches incorporating a combination of immunotherapy with traditional treatments for prostate cancer is presented.     

Prognostic Index Model for Progression-Free Survival in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Plus Prednisone

Background

Radiographic progression-free survival (rPFS) is associated with overall survival (OS) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients. Using readily assessable baseline clinical and laboratory parameters, we developed a prognostic index model for rPFS in chemotherapy-naïve mCRPC patients without visceral disease who were treated with abiraterone acetate plus prednisone.

Classical and Alternative Nuclear Factor-κB Pathways: A Comparison among Normal Prostate, Benign Prostate Hyperplasia and Prostate Cancer

Nuclear factor-κB (NF-κB) is controlled by the classical and alternative NF-κB pathways, the role of which in prostate cancer (PCa) is not clearly defined. To provide this missing translational link, we compared the classical and alternative NF-κB pathways in normal prostate, benign prostate hyperplasia (BPH) and PCa. Prostate specimens were divided into three groups: group A, PCa (n?=?68); group B, BPH (n?=?60); and group C, normal prostates (n?=?15). The gene expression levels of NF-κB1 and NF-κB2 were determined by real-time quantitative RT-PCR. Additionally, we analyzed the expression and sub-cellular localization of phosphorylated P50 (p-P50) and phosphorylated P52 (p-P52) proteins by immunohistochemical staining. Furthermore, associations were made between NF-κB pathway proteins and patients' prognosis. Compared with BPH and normal prostate tissues, the expression of NF-κB1 gene was differentially down-regulated by >1.5-fold, whereas NF-κB2 gene was differentially up-regulated by >2-fold in PCa tissues. The proportion of p-P50 positive patients in group A (26.5%) was significantly lower than in group B (88.3%, p?=?0.005) and C (100%, p?=?0.002). The proportion of p-P52 positive patients in group A (42.6%) was significantly higher than in group B (11.7%, p?=?0.009) and C (6.7%, p?=?0.008). Comparison of the survival curves in group A according to p-P52 expression showed a significant difference between positive and negative patients. The p-P52 positive patients showed worse prognosis (p?=?0.019). Our findings suggest for the first time that the classical and alternative NF-κB pathways have an important role in PCa. p-P52 might be a predictor of poor prognosis for PCa.     

Outcomes in Patients With Non–small-cell Lung Cancer With Brain Metastases Treated With Pembrolizumab-based Therapy

BackgroundPatients with metastatic non–small-cell lung cancer (mNSCLC) and untreated brain metastases (BM) have been excluded from most trials of immune checkpoint inhibitors (ICIs). Real-world evidence on efficacy and survival outcomes of ICIs in patients with BM is limited.Patients and MethodsWe conducted a single-center retrospective study of patients with mNSCLC treated with pembrolizumab with or without chemotherapy and compared progression-free survival (PFS) and overall survival (OS) between patients with and without BM using Kaplan-Meier and Cox methodology. We also characterized systemic and intracranial objective response rate (ORR) and treatment details, including timing of cranial irradiation.ResultsBetween Augutst 2013 and December 2018, 570 patients with mNSCLC treated with pembrolizumab-based therapy were analyzed. Of 126 (22.1%) patients with BM, 96 (76.2%) had treated BM (local therapy prior to pembrolizumab), and 30 (23.8%) had untreated BM. Of patients with untreated BM, 17 (56.7%) underwent radiation within 30 days after pembrolizumab initiation. In the remaining 13 (43.3%) treated with pembrolizumab-based therapy alone, intracranial ORR was 36.4%. Patients with and without BM did not have significantly different systemic ORR (27.8% vs. 29.7%; P = .671), PFS (mPFS 9.2 vs. 7.7 months; P = .609), or OS (mOS 18.0 vs. 18.7 months; P = .966). Factors associated with improved survival on Cox analysis included female gender, performance status, adenocarcinoma histology, and first-line therapy.ConclusionsPatients with BM did not have inferior survival to patients without BM after treatment with pembrolizumab-based therapy. In the current era, BM may not automatically confer inferior survival, and should not exclude patients from receiving pembrolizumab-based therapy.     

Prostate Cancer Lesions by Zone and Race: Does Multiparametric MRI Demonstrate Racial Difference in Prostate Cancer Lesions for African American Men?

African American (AA) men have increased risk of prostate cancer diagnosis and mortality, but the cause remains unknown. MRI fusion improves diagnosis of localized prostate cancer, particularly in anterior lesions; however, cost and access are limited in a community practice setting. By utilizing a diverse cohort of veterans with equal access to care in a single payer system, we describe prostate cancer detection. We queried a prospectively maintained institutional review board-approved database of men undergoing prostate biopsy for untreated prostate cancer. We included all consecutive patients from October 2017 to February 2020. Statistical analysis including Kaplan–Meier Curves, Fisher’s exact test, and Forest plot was performed. From 246 consecutive patients, 166 were AA and 80 were non-AA. There were similar distributions of PSA, PSAD, and number of targetable lesions between the AA and non-AA cohort (p > 0.05 for all). We found no difference in location on MRI between race groups. There was similar cancer detection, focusing on anterior lesions and rate of positive Gleason grade (≥GG1) and clinically significant (≥GG2) cancer between cohorts. In a predominant AA cohort of veterans, we found similar distribution of location for MRI-targeted lesions, along with rates of tumor detection and aggressiveness of disease. In this single payer veteran population, we did not identify specific biologic differences inherent to tumor detection between AA and non-AA patients.     

Is There an Optimal Comorbidity Index for Prostate Cancer?

BACKGROUND: Comorbidity is an important consideration in oncology practice, particularly among older patients. Although a variety of comorbidity indices have been employed in research studies, it is unclear whether any one index is preferred. METHODS: An age-stratified random sample of 345 men (mean age of 69 years) who were newly diagnosed with prostate cancer were identified from a cancer registry in Ontario, Canada. Comorbidity and treatment information were obtained from chart review. Four comorbidity indices were utilized: Charlson Index, Diagnosis Count, Index of Coexistent Disease (ICED), and number of medications. Logistic regression analysis was used to compare the performance of comorbidity measures with respect to predicting receipt of curative treatment (radical prostatectomy or radiotherapy) and overall 6-year survival. Multivariable model performance including each of the comorbidity measures was compared by calculating the area under the receiver operating characteristic curve (AUROC). RESULTS: Among men with localized disease (n = 231), in models adjusted for age, Gleason score, and prostate-specific antigen level, only the Charlson Index was found to be a statistically significant predictor of receipt of curative treatment (P < .05), although all comorbidity indices had similar AUROC in adjusted models. After a median follow-up of 6.5 years, 116 of 345 men (33.6%) had died. In adjusted models, all 4 comorbidity indices performed similarly in predicting overall survival. CONCLUSIONS: Although comorbidity is an important predictor of both curative treatment and overall survival in prostate cancer, the optimal comorbidity index for use in research remains unclear. Selecting the optimal comorbidity index may depend on both the specific patient population and the outcome being considered.     

Antibody-Drug Conjugates in Prostate Cancer: Where Are we?

Antibody-drug conjugates (ADCs) reflect a new promising approach in prostate cancer, even more so after the practice-changing results in other malignancies, either hematologic or solid. ADCs consist of monoclonal antibodies (mAb) targeted at specific antigens overly expressed on cancer cells compared to normal cells. A cytotoxic payload is attached to the mAb using a stable linker. In prostate cancer, PSMA, STEAP1, TROP2, CD46 and B7-H3 are antigens currently being studied as targets for ADCs. In this paper, we discuss the composition of ADCs and focus on their application and challenges as treatment options in prostate cancer.