ABSTRACT
The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to train an artificial intelligence (AI)-based algorithm to grade prostate cancer in specimens from patients who underwent radical prostatectomy (RP) and to assess the correlation of AI-estimated proportions of different Gleason patterns with biochemical recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS). Training and validation of algorithms for cancer detection and grading were completed with three large datasets containing a total of 580 whole-mount prostate slides from 191 RP patients at two centers and 6218 annotated needle biopsy slides from the publicly available Prostate Cancer Grading Assessment dataset. A cancer detection model was trained using MobileNetV3 on 0.5â¯mmâ¯×â¯0.5â¯mm cancer areas (tiles) captured at 10× magnification. For cancer grading, a Gleason pattern detector was trained on tiles using a ResNet50 convolutional neural network and a selective CutMix training strategy involving a mixture of real and artificial examples. This strategy resulted in improved model generalizability in the test set compared with three different control experiments when evaluated on both needle biopsy slides and whole-mount prostate slides from different centers. In an additional test cohort of RP patients who were clinically followed over 30â¯years, quantitative Gleason pattern AI estimates achieved concordance indexes of 0.69, 0.72, and 0.64 for predicting RFS, MFS, and OS times, outperforming the control experiments and International Society of Urological Pathology system (ISUP) grading by pathologists. Finally, unsupervised clustering of test RP patient specimens into low-, medium-, and high-risk groups based on AI-estimated proportions of each Gleason pattern resulted in significantly improved RFS and MFS stratification compared with ISUP grading. In summary, deep learning-based quantitative Gleason scoring using a selective CutMix training strategy may improve prognostication after prostate cancer surgery.
ABSTRACT
Elucidating the cellular immune components underlying aggressive prostate cancer, especially among African American (AA) men who are disproportionately affected by this disease compared with Caucasian American (CA) men, will support more inclusive precision medicine treatment strategies. We aimed to evaluate which immune-related genes and cell types are differentially expressed in AA tumors and how immunobiology impacts prostate cancer progression. We purified nucleic acid from tumor biopsies, obtained following radical prostatectomy, from 51 patients (AA = 26, CA = 25). Gene expression was measured using the NanoString platform from which we estimated immune cell abundances and assessed differences between groups based on clinicopathologic data. Product-limit estimates determined associations with biochemical recurrence (BCR)-free and metastasis-free survival. DVL2 and KLRC2 were significantly upregulated in CA tumors and were also associated with worse disease progression. No significant differences in immune cell abundances by race were observed. Highly significant reductions in abundances of mast cells versus tumor-infiltrating lymphocytes (TIL) were found in men with high-grade pathologies and in men who later developed metastases. Low ratios of mast cells versus TILs were associated with worse BCR-free survival and metastasis-free survival. Although estimated immune cell abundances were not different by race, we identified genes involved in metabolism and natural killer cell functions that were differentially expressed between AA and CA tumors. Among the entire cohort, depletion of mast cells within prostatectomy tumors was characteristic of advanced disease and susceptibility to disease progression. Significance: Our findings demonstrate that there are immune-related genes and pathways that differ by race. Impaired intratumoral cellular immune composition, especially for TIL-normalized mast cells, may be vital in predicting and contributing to prostate cancer disease progression.
Subject(s)
Military Personnel , Prostatic Neoplasms , Male , Humans , Mast Cells/pathology , Prostate-Specific Antigen , Prognosis , Neoplasm Recurrence, Local/genetics , Prostatic Neoplasms/genetics , Disease Progression , NK Cell Lectin-Like Receptor Subfamily CABSTRACT
Background: Localized prostate cancer (PCa) treatment is associated with reduced health-related quality of life (HRQoL). Current literature is limited by short-term follow-up. Objective: To prospectively evaluate the 5-yr HRQoL outcomes in men undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), or active surveillance (AS). Design setting and participants: We prospectively evaluated HRQoL in patients with low-risk/favorable intermediate-risk PCa enrolled in the Center for Prostate Disease Research multicenter database between 2007 and 2017. Intervention: Of 1012 patients included in the study, 252 (24.9%) underwent AS, 557 (55.0%) RP, and 203 (20.0%) EBRT. Patients complete the Expanded Prostate Cancer Index Composite and the 36-item Medical Outcomes Study Short Form at baseline and thereafter each year up to 5 yr after treatment. Outcome measurements and statistical analysis: Temporal changes in HRQoL were compared between treatments and were modeled using linear regression models adjusted for baseline HRQoL, demographic, and clinical characteristics. Results and limitations: RP showed the least irritative symptoms and worse incontinence in comparison with AS (p < 0.001 for both subdomains) or EBRT (p < 0.001 for both subdomains) at all time points. RP sexual domain score was worse than the scores of AS (mean difference 22.3 points, 95% confidence interval [CI] 10.5-27.8, p < 0.001) and EBRT (mean difference 16.9 points, 95% CI 12.5-20.3, p < 0.001) during years 1-3 and not different from that of EBRT (mean difference 2.9 points, 95% CI -4.8 to 8.3, p = 0.3) at years 4 and 5. Bowel function and bother were worse for EBRT than for AS (p < 0.001 for both subdomains) and RP (p < 0.001 for both subdomains) at all time points. During the 3-5-yr period, AS demonstrated the worst decline in all mental health domains (p < 0.001 in comparison with both EBRT and RP). Conclusions: RP results in worse long-term urinary function and incontinence, but in less irritative and obstructive symptoms than EBRT and AS. Sexual domain scores were least affected by AS, while RP shows similar scores to EBRT at long term. Long-term HRQoL changes are critical for advising patients. Patient summary: We evaluated long-term health-related quality of life (HRQoL) in a large US population treated for localized prostate cancer. HRQoL outcomes varied according to treatment modality and time. These changes should inform patients about their expected outcomes following treatment.
ABSTRACT
INTRODUCTION: Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT). METHODS: Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey. RESULTS: In 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p < 0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT. CONCLUSION: AA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men.
Subject(s)
Black or African American , Prostatic Neoplasms , Quality of Life , Humans , Male , Prostatectomy/methods , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/surgery , Treatment Outcome , Healthcare DisparitiesABSTRACT
PURPOSE: To compare 5-year health-related quality of life (HRQoL) outcomes between prostate cancer (CaP) patients who underwent robotic-assisted laparoscopic radical prostatectomy (RALP) versus open radical retropubic prostatectomy (RRP) and assess for racial disparities between Caucasian American (CA) and African American (AA) men undergoing surgery. METHODS: A prospective cohort study of HRQoL data was conducted on patients diagnosed with CaP from 2007 to 2017 and enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database. Using the EPIC and SF-36 instruments, changes in urinary, sexual, bowel, and hormonal domains, as well as physical and mental component summary scores were compared across surgery type (RALP versus RRP) at pre-treatment ("baseline"), and annually for 5 years. We further compared HRQoL outcomes in CA and AA men undergoing surgery. Longitudinal HRQoL patterns were modeled using generalized estimating equations (GEE), adjusting for baseline HRQoL and other characteristics. RESULTS: 448 CaP patients (22% AA) met study inclusion criteria, 66% underwent RALP and 34% underwent RRP. At baseline, HRQoL domains were comparable across treatment group (RALP vs. RRP). In the adjusted low-risk cohort, there were only three time points that met a statistically significant HRQoL difference in EPIC scores between RALP and RRP. Urinary function score during year 4 of follow-up showed a 7.5 (95% CI 3.1-11.9, P = 0.01) points difference in favor of RRP. Bowel bother scores favored RRP in year 1 with a difference of 3.1 (95% CI 0.7-5.4, P = 0.04) points, and in year 5 with a difference of 3.8 (95% CI 1.1-6.4, P = 0.03) points. In the intermediate/high-risk cohort, there were no statistically significant differences in any of the domain scores between RALP and RRP during follow-up. CONCLUSIONS: The robotic and open approach to radical prostatectomy led to comparable HRQoL outcomes at a follow-up length of 60 months. No HRQoL racial disparities were found between AA and CA men during long-term follow-up.
Subject(s)
Laparoscopy , Prostatic Neoplasms , Robotic Surgical Procedures , Humans , Laparoscopy/methods , Male , Prospective Studies , Prostate , Prostatectomy/methods , Prostatic Neoplasms/surgery , Quality of Life , Robotic Surgical Procedures/methods , Treatment OutcomeABSTRACT
OBJECTIVES: To investigate impact of age and race on health-related quality of life (HRQoL) in men undergoing radical prostatectomy (RP) using a prospectively maintained, racially diverse cohort. METHODS: The Center for Prostate Disease Research Multicenter National Database was used to identify patients receiving RP from 2007-2017. The Expanded PCa Index Composite and 36 Item Short-Form Health Survey were completed at baseline and regular intervals. Groups were stratified based on age: <60, 60-70, >70. Longitudinal patterns in HRQoL were assessed using linear regression models, adjusting for baseline HRQoL, demographics, and clinical characteristics. RESULTS: In 626 patients undergoing RP, 278 (44.4%) were <60, 291 (46.5%) were 60-70, 57 (9.1%) were >70. Older men had worse baseline urinary bother (P<.01) and sexual HRQoL (P<.01). Baseline urinary function was similar for older and younger men. Post-RP urinary and sexual HRQoL was significantly lower in men >70. However, when adjusting for baseline HRQoL, race, NCCN risk, and comorbidities, no difference was found between age groups in urinary function or bother, or sexual function. Sexual bother was worse in older men until 48 months post-operatively but subsequently improved to levels similar to younger patients. Race independently affected HRQoL outcomes with older African American men reporting worse urinary function and sexual bother. CONCLUSIONS: When accounting for baseline HRQoL, age does not independently predict worse HRQoL outcomes. Older and younger men experience similar declines in urinary and sexual domain scores after RP. Our findings may be used to better inform patients regarding their expected post RP HRQoL and guide treatment decision-making.
Subject(s)
Prostatic Neoplasms , Urination Disorders , Aged , Humans , Male , Prostate , Prostatectomy/adverse effects , Prostatic Neoplasms/therapy , Quality of Life , Urination Disorders/etiologyABSTRACT
BACKGROUND: Prostate cancer patients diagnosed with low- and intermediate-risk disease have several treatment options. Decisional regret after treatment is a concern, especially when poor oncologic outcomes or declines in health-related quality of life (HRQoL) occur. This study assessed determinants of longitudinal decisional regret in prostate cancer patients attending a multidisciplinary clinic and treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), or active surveillance (AS). METHODS: Patients newly diagnosed with prostate cancer at the Walter Reed National Military Medical Center who attended a multidisciplinary clinic were enrolled into a prospective study from 2006 to 2014. The Decision Regret Scale was administered at 6, 12, 24, and 36 months posttreatment. HRQoL was also assessed at regular intervals using the Expanded Prostate Cancer Index Composite and 36-item RAND Medical Outcomes Study Short Form questionnaires. Adjusted probabilities of reporting regret were estimated via multivariable logistic regression fitted with generalized estimating equations. RESULTS: A total of 652 patients met the inclusion criteria (395 RP, 141 EBRT, 41 BT, 75 AS). Decisional regret was consistently low after all of these treatments. In multivariable models, only African American race (odds ratio, 1.67; 95% confidence interval, 1.12-2.47) was associated with greater regret across time. Age and control preference were marginally associated with regret. Regret scores were similar between RP patients who did and did not experience biochemical recurrence. Declines in HRQoL were weakly correlated with greater decisional regret. CONCLUSION: In the context of a multidisciplinary clinic, decisional regret did not differ significantly between treatment groups but was greater in African Americans and those reporting poorer HRQoL. Cancer 2017;123:4252-4258. © 2017 American Cancer Society.
Subject(s)
Decision Making , Emotions , Prostatic Neoplasms/psychology , Prostatic Neoplasms/therapy , Quality of Life , Black or African American/psychology , Black or African American/statistics & numerical data , Age Factors , Aged , Brachytherapy/psychology , Humans , Logistic Models , Male , Middle Aged , Prospective Studies , Prostatectomy/psychology , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/pathology , Radiotherapy/psychology , Risk , Time Factors , Watchful WaitingABSTRACT
BACKGROUND: Patients diagnosed with prostate cancer (PCa) are presented with several treatment options of similar efficacy but varying side effects. Understanding how and why patients make their treatment decisions, as well as the effect of treatment choice on long-term outcomes, is critical to ensuring effective, patient-centered care. This study examined treatment decision-making in a racially diverse, equal-access, contemporary cohort of patients with PCa counseled on treatment options at a multidisciplinary clinic. METHODS: A prospective cohort study was initiated at the Walter Reed National Military Medical Center (formerly Walter Reed Army Medical Center) in 2006. Newly diagnosed patients with PCa were enrolled before attending a multidisciplinary clinic. Patients completed surveys preclinic and postclinic to assess treatment preferences, reasons for treatment choice, and decisional regret. RESULTS: As of January 2014, 925 patients with PCa enrolled in this study. Surgery (54%), external radiation (20%), and active surveillance (12%) were the most common primary treatments for patients with low- and intermediate-risk PCa, whereas patients with high-risk PCa chose surgery (34%) or external radiation with neoadjuvant hormones (57%). Treatment choice differed by age at diagnosis, race, comorbidity status, and calendar year in both univariable and multivariable analyses. Patients preferred to play an active role in the decision-making process and cited doctors at the clinic as the most helpful source of treatment-related information. Almost all patients reported satisfaction with their decision. CONCLUSIONS: This is one of the first prospective cohort studies to examine treatment decision-making in an equal-access, multidisciplinary clinic setting. Studies of this cohort would aid in understanding and improving the PCa decision-making process.
Subject(s)
Decision Making , Hospitals, Military , Patient Care Team , Prostatic Neoplasms/therapy , Aged , Humans , Male , Middle Aged , Multivariate Analysis , Patient Participation , Prospective Studies , Surveys and QuestionnairesABSTRACT
UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Little is known as to the potential for over-treatment of young men diagnosed with prostate cancer. We show that for men aged ≤55 years with PSA screen-detected disease, 45% of the tumours are classified as very low risk and 85% of these have favourable pathology, yet most are actively treated. These findings raise the spectre of over-treatment for a group of men likely to be affected by treatment side-effects. OBJECTIVE: To identify a population of young men (aged <55 years at diagnosis) with very-low-risk prostate cancer (stage cT1c, with prostate-specific antigen [PSA] density of <0.15 ng/mL/g, Gleason score ≤6, and ≤2 positive biopsy cores with <50% tumour involvement) that may be candidates for active surveillance (AS). PATIENTS AND METHODS: We queried a Department of Defense tumour registry and hard-copy records for servicemen diagnosed with prostate cancer from 1987 to 2010. Statistical analyses were undertaken using Fisher's exact and chi-square testing. RESULTS: From 1987-1991 and 2007-2010, PSA screen-detected tumours diagnosed in men aged ≤55 years rose >30-fold. Data for a subset of men (174) with PSA screen-detected cancer were evaluable for disease risk assessment. Of the 174 men with screen-detected disease, 81 (47%) had very-low-risk disease. Of that group, 96% (78/81) selected treatment and, of 57 men undergoing radical prostatectomy (RP), the tumours of 49 (86%) carried favourable pathology (organ confined, <10% gland involvement, Gleason ≤6). CONCLUSIONS: Nearly half of young men with PSA screen-detected prostate cancer are AS candidates but the overwhelming majority seek treatment. Considering that many tumours show favourable pathology at RP, there is a possibility that these patients may benefit from AS management.
Subject(s)
Biomarkers, Tumor/blood , Early Detection of Cancer/methods , Population Surveillance , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/immunology , Adult , Age Distribution , Humans , Male , Middle Aged , Military Personnel , Neoplasm Grading , Patient Selection , Predictive Value of Tests , Prostatic Neoplasms/epidemiology , Risk Assessment , United States/epidemiologyABSTRACT
OBJECTIVE: To determine the health-related quality of life (HRQoL) impact of prostate cancer interventions at 2 years post-treatment, and between the 12- and 24-month interval, to better characterize this measure. MATERIALS AND METHODS: Patients treated at the Center for Prostate Disease Research between June 2003 and February 2010 were offered enrollment into a HRQoL study that entailed a baseline evaluation before prostate biopsy and at 3, 6, 9, 12, 18, 24, and 30 months thereafter. The instruments used were the Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short-Form 36 (SF-36). A Student's t-test and ANOVA were used to examine the association between HRQoL scores, patient demographic, and disease features. Multivariable regression models were used to analyze change over time. Estimates of risk, corresponding confidence intervals, and P values are presented for these longitudinal findings. RESULTS: The study group was comprised of 595 patients. African Americans (AA) had slightly lower baseline raw scores in all EPIC and SF-36 HRQoL domains, but on bivariate analysis, there was no statistical difference in change of scores over time. Radical prostatectomy (RP) led to the greatest decline in urinary function. Bowel function significantly worsened with the addition of hormone therapy (HT) to external beam radiation therapy (EBRT). Sexual bother and function had a marked decline in all active treatment options. Despite these changes, there were no differences in overall satisfaction. SF-36 domains were not affected by RP, whereas EBRT and EBRT + HT had universal impact. For the 12- to 24-month interval, specifically, patients who underwent EBRT fared worse over this time period, showing continued worsening of urinary bother, hormonal function, physical role, physical component summary, and overall satisfaction. Patients who underwent RP did not show any further decline in the 12- to 24-month interval, but instead showed improvement. CONCLUSIONS: Because of the protracted nature of recovery after surgery, delayed onset of effects from radiation, potential interval decline secondary to age-related symptoms, and longevity of patients with prostate cancer, determination of long-term HRQoL outcomes is integral. Counseling with regard to these outcomes should be balanced with oncologic expectations from treatment.
Subject(s)
Health Status , Prostatic Neoplasms/therapy , Quality of Life , Surveys and Questionnaires , Black or African American/statistics & numerical data , Asian People/statistics & numerical data , Educational Status , Hispanic or Latino/statistics & numerical data , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/pathology , Regression Analysis , Social Class , Time Factors , Treatment Outcome , White People/statistics & numerical dataABSTRACT
INTRODUCTION: In this review, the International Agency for Research on Cancer's cancer epidemiology databases were used to examine prostate cancer (PCa) age-standardized incidence rates (ASIR) in selected Asian nations, including Cancer Incidence in Five Continents (CI5) and GLOBOCAN databases, in an effort to determine whether ASIRs are rising in regions of the world with historically low risk of PCa development. MATERIALS AND METHODS: Asian nations with adequate data quality were considered for this review. PCa ASIR estimates from CI5 and GLOBOCAN 2008 public use databases were examined in the four eligible countries: China, Japan, Korea and Singapore. Time trends in PCa ASIRs were examined using CI5 Volumes I-IX. RESULTS: While PCa ASIRs remain much lower in the Asian nations examined than in North America, there is a clear trend of increasing PCa ASIRs in the four countries examined. CONCLUSION: Efforts to systematically collect cancer incidence data in Asian nations must be expanded. Current CI5 data indicate a rise in PCa ASIR in several populous Asian countries. If these rates continue to rise, it is uncertain whether there will be sufficient resources in place, in terms of trained personnel and infrastructure for medical treatment and continuum of care, to handle the increase in PCa patient volume. The recommendation by some experts to initiate PSA screening in Asian nations could compound a resource shortfall. Obtaining accurate estimates of PCa incidence in these countries is critically important for preparing for a potential shift in the public health burden posed by this disease.
ABSTRACT
OBJECTIVE: ⢠To describe metastasis-free survival (MFS) and overall survival (OS) among men with prostate-specific antigen (PSA)-recurrent prostate cancer after radical prostatectomy who did not receive additional therapy until metastasis, using a multicentre database capturing a wide ethnic mix. PATIENTS AND METHODS: ⢠A retrospective analysis of the Center for Prostate Disease Research National Database (comprised of five US military hospitals and one civilian centre) was performed for patients with PSA relapse (≥ 0.2 ng/mL) after radical prostatectomy who had no additional therapy until the time of radiographic metastatic disease. ⢠We investigated factors influencing metastasis and all-cause mortality using univariate and multivariate Cox regression analysis. RESULTS: ⢠There were a total of 346 men who underwent radical prostatectomy between May 1983 and November 2008 and fulfilled the entry criteria. All patients had information on survival and 190 men had information on metastasis. Among patients with survival data (n= 346), 10-year OS was 79% after a median follow-up of 8.6 years from biochemical recurrence. ⢠Among men with metastasis data (n= 190), 10-year MFS was 46% after a median follow-up of 7.5 years. ⢠In Cox regressions, four clinical factors (Gleason score, pathological stage, time to PSA relapse and PSA doubling time), as well as age, were predictive of OS and/or MFS in univariate analysis, although only PSA doubling time (≥ 9 vs 3-8.9 vs <3 months) remained independently predictive of these outcomes in multivariate analysis (P < 0.001). CONCLUSIONS: ⢠This multicentre multi-ethnic dataset shows that OS and MFS can be extensive for men with PSA-recurrent prostate cancer, even in the absence of further therapy before metastasis. ⢠This unique patient cohort, the second largest of its type after the Johns Hopkins cohort, confirms that PSA doubling time is the strongest determinant of OS and MFS in men with PSA-recurrent disease. ⢠Longer follow-up and more events will be required to determine whether other variables may also contribute to these outcomes.
Subject(s)
Neoplasm Recurrence, Local/mortality , Prostate-Specific Antigen/metabolism , Prostatectomy/mortality , Prostatic Neoplasms/surgery , Disease-Free Survival , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Staging/mortality , Prostatectomy/methods , Prostatic Neoplasms/blood , Prostatic Neoplasms/mortality , Retrospective Studies , Risk FactorsABSTRACT
The objective of this study was to assess the incidence of circulating tumor cells (CTCs) in prostate cancer patients with low-volume tumors (less than 0.5 cc) after radical prostatectomy (RP). Blood samples were collected from 64 RP patients to assess the incidence of CTCs following RP. The specimens were processed by whole-mount section. Clinicopathological data (e.g. patient age, race, specimen weight, tumor volume, grade, stage and surgical margin status) and follow-up PSA data were compared to CTC status. Of the 64 RP patients, nine had 'low-volume prostate cancer'. Seven of these patients had detectable levels of CTCs. In two of the seven patients with detectable CTCs, PSA elevation was also observed. Isolation and detection of circulating epithelial cells is possible in low-volume prostate cancer patients. In the setting of low-volume prostate cancer, CTCs may be associated with the presence of detectable PSA levels. However, the detection of CTCs did not predict PSA failure.
Subject(s)
Neoplastic Cells, Circulating/pathology , Prostatic Neoplasms/pathology , Adult , Aged , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Tumor BurdenABSTRACT
OBJECTIVES: To identify racial and demographic factors that influence treatment choice and its resulting impact on health-related quality of life (HRQoL) for prostate cancer patients. METHODS: Patients presenting to an equal access, military, multidisciplinary prostate cancer clinic composed the study group. The Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short Form 36 were the instruments used. Evaluation was performed before treatment and every 3 months after treatment. RESULTS: The study group comprised 665 patients. Caucasians were 3-fold more likely to choose surgery (radical prostatectomy [RP]) over external beam radiation therapy (EBRT). Patients who earned more than $100,000 annually disproportionately chose RP (P < .0001). Similarly, those having a graduate school degree disproportionally chose RP (P < .0001). Patients undergoing RP had the greatest risk of urinary function decline (P < .0001) and sexual bother (P = .0003). African Americans (AA) had a greater risk of urinary function decline irrespective of treatment choice. Patients undergoing EBRT had equivalent urinary function to expectant management (EM) at 12 months (P < .0001). Brachytherapy was the only treatment that posed an increased risk of urinary bother decline when compared with EM (P = .0217). EBRT alone did not show significant decrement in sexual function when compared with EM. CONCLUSIONS: RP was chosen by patients of Caucasian ethnicity and patients with higher income and education level, despite providing the greatest risk of HRQoL decline. EBRT had no significant impact on urinary function, sexual function, or sexual bother scores at 12 months. EBRT may be offered to older patients with minimal HRQoL impact. Pretreatment counseling of HRQoL outcomes is essential to overall prostate cancer management.
Subject(s)
Patient Preference , Prostatic Neoplasms/therapy , Quality of Life , Black or African American , Aged , Decision Making , Educational Status , Humans , Income , Male , Middle Aged , Outpatient Clinics, Hospital , Patient Preference/ethnology , Prostatectomy , Prostatic Neoplasms/radiotherapy , Surveys and Questionnaires , White PeopleABSTRACT
PURPOSE: Prevalent gene fusions in prostate cancer involve androgen-regulated promoters (primarily TMPRSS2) and ETS transcription factors (predominantly ETS-regulated gene (ERG)], which result in tumor selective overexpression of ERG in two thirds of patients. Because diverse genomic fusion events lead to ERG overexpression in prostate cancer, we reasoned that it may be more practical to capture such alterations using an assay targeting ERG sequences retained in such gene fusions. This study evaluates the potential of an assay quantitating ERG mRNA in post-digital rectal exam (DRE) urine for improving prostate cancer detection. EXPERIMENTAL DESIGN: Patients scheduled to undergo transrectal ultrasound-guided needle biopsy of the prostate were prospectively enrolled. On the day of biopsy, patients provided a urine sample immediately following a DRE. Urine ERG mRNA was measured and normalized to urine prostate-specific antigen (PSA) mRNA using the DTS 400 system. Demographic traits, clinical characteristics and biopsy results were analyzed for association with urine ERG score. RESULTS: The study was conducted on 237 patients. Prostate cancer was shown on biopsy in 40.9% of study subjects. A higher urine ERG score associated significantly with malignancy on biopsy (P = 0.0145), but not with clinical stage or Gleason score. Urine ERG score performed best in Caucasians and in men with a PSA of Subject(s)
Biomarkers, Tumor/analysis
, Prostatic Neoplasms/genetics
, Prostatic Neoplasms/urine
, RNA, Messenger/analysis
, Trans-Activators/genetics
, Trans-Activators/urine
, Aged
, Area Under Curve
, Biomarkers, Tumor/genetics
, Biomarkers, Tumor/urine
, Humans
, Male
, Middle Aged
, Neoplasm Staging
, Prostatic Neoplasms/pathology
, RNA, Messenger/genetics
, RNA, Messenger/urine
, ROC Curve
, Sensitivity and Specificity
, Transcriptional Regulator ERG
ABSTRACT
PURPOSE: PCA3 is a prostate specific, nonprotein coding RNA that is over expressed in prostate cancer. Recent studies showed the diagnostic potential of a urine based PCA3 for predicting biopsy outcome. We assessed the relationship between urine PCA3 and pathological features in whole mount radical prostatectomy specimens. MATERIALS AND METHODS: Post-digital rectal examination urine specimens were obtained from 72 men with prostate cancer before radical prostatectomy. PCA3 and PSA mRNA were measured. The ratio of PCA3 to PSA mRNA was recorded as a PCA3 score and correlated with data on each prostate specimen. RESULTS: Patients with extracapsular extension had a significantly higher median PCA3 score than patients without extracapsular extension (48.8 vs 18.7, p = 0.02). PCA3 score significantly correlated with total tumor volume (r = 0.38, p <0.01). On multivariate analysis PCA3 score was an independent predictor of extracapsular extension (p = 0.01) and total tumor volume less than 0.5 cc (p = 0.04). At a cutoff PCA3 score of 47 extracapsular extension was predicted with 94% specificity and an 80% positive predictive value. When combined with serum PSA and biopsy Gleason score, the ROC AUC for predicting extracapsular extension was 0.90. CONCLUSIONS: PCA3 detected in the post-digital rectal examination urine of patients with prostate cancer correlated with pathological findings. Therefore, it could provide prognostic information. To our knowledge this is the first report of a molecular urine assay that predicts extracapsular extension.