Background

The aim of this study was to determine the optimal treatment for a patient with newly diagnosed prostate cancer weighing the individual's risk of disease progression against his risk of non-cancer death.

Methods

We developed a predictive model incorporating clinicopathological tumor variables, patient age, comorbidity status, and primary treatment modality. We identified 6091 patients with clinically-localized prostate cancer managed with radical prostatectomy (n=4117) or radiation therapy (n=1974) from the Cancer of the Prostate Strategic Urologic Research Endeavor database. Fine and Gray competing-risks proportional hazards regression models were used to calculate the risks of prostate cancer-specific mortality (PCSM) and non-prostate cancer death and to generate a nomogram.

Results

The median follow-up after treatment was 53 months (interquartile range 30, 80 months). In total, 983 men died during follow-up, including 167 who died of prostate cancer and 816 who died of non-prostate cancer causes. On multivariate analysis, higher Cancer of the Prostate Risk Assessment score and primary treatment with radiation were associated with an increased risk of PCSM, whereas older age, African-American race, and treatment with radiation predicted non-prostate cancer death. The number of comorbidities and receipt of androgen deprivation therapy correlated with an increased risk of non-prostate cancer death, but not PCSM. The resulting nomogram allows quantification and comparison of the 10-year risk of PCSM and non-prostate cancer death.

Conclusions

Integrating clinicopathological variables with comorbid conditions in a competing-risks model affords quantification and comparison of relative probabilities of PCSM and non-prostate cancer death following treatment. Our model thereby facilitates an individualized approach for counseling patients regarding prostate cancer management.

Background African American (AA) men suffer a higher prostate cancer (PCa) burden than other groups. Objective We aim to determine the impact of race on the risk of upgrading, upstaging, and positive surgical margins (PSM) at radical prostatectomy (RP) among men eligible for active surveillance. Design, setting, and participants We studied men with low-risk PCa treated with RP at two centers. Low clinical risk was defined by National Comprehensive Cancer Network criteria. Outcome variables were upgrading, upstaging, and PSMs at surgery. Associations between race and the outcomes were evaluated with logistic regression adjusted for age, relationship status, diagnostic prostate-specific antigen level, percentage of positive biopsy cores, surgical approach, year of diagnosis, and clinical site. Results and limitations Of 9304 men diagnosed with PCa, 4231 were low risk and underwent RP within 1 yr. Men were categorized as AA (n = 273; 6.5%), Caucasian (n = 3771; 89.1%), or other racial/ethnic group (Other; n = 187; 4.4%). AA men had a significantly younger mean age (58.7 yr; standard deviation: ±7.06), and fewer (85%) were married or had a partner. Upgrading (34%) and upstaging (13%) rates did not significantly differ among the groups. The PSM rate was significantly higher in AA men (31%) than in the Caucasian (21%) and Other (20%) groups (p < 0.01). We found an association between race group and PSM rate (p < 0.03), with higher odds of PSMs in AA men versus Caucasian men (odds ratio [OR]: 1.64; 95% confidence interval [CI], 1.08-2.47). No statistically significant associations between race and rates of upgrading and upstaging were found. This study was limited by the relatively low proportion of AA men in the cohort. Conclusions Among clinically low-risk men who underwent RP, AA men had a higher likelihood of PSMs compared with Caucasian men. We did not find statistically significantly different rates of upgrading and upstaging between the race groups. Patient summary We analyzed two large groups of men with what appeared to be low-risk prostate cancer based on the initial biopsy findings. The likelihood of finding worse disease (higher grade or stage) at the time of surgery was similar across different racial groups.

Background Men aged >65 yr are less likely to receive local therapy for prostate cancer (PCa), perhaps because of concerns about quality-of-life (QOL) outcomes. Objective To describe QOL before and after PCa treatment in men of varying ages. Design, setting, and participants Participants enrolled in CaPSURE who underwent radical prostatectomy, brachytherapy, external beam radiation, androgen deprivation therapy, or active surveillance for localized PCa. Outcome measurements and statistical analysis QOL changes over time were assessed among age groups using repeated-measures mixed models adjusted for race, year, clinical risk, treatment, comorbidities, and an age-time interaction term. Differences are reported as adjusted least-square means and percentage decline. Secondary analyses evaluated age and QOL for local (prostatectomy, radiation) compared to nonlocal treatment (hormonal, surveillance). Results and limitations Older men had lower mean unadjusted pre- and post-treatment QOL scores for nearly all domains. Of the domains evaluated, adjusted mean sexual function, sexual bother, and urinary function showed greater declines from baseline to 2 yr. At 2 yr, more men <60 yr than those >70 yr experienced declines in urinary function (14% vs 9%) and sexual bother (39% vs 17%). Declines in these domains were also greater for local than for nonlocal treatment. Conclusions Definitive treatment for localized disease should not be deferred for older men because of fears regarding QOL declines. Younger men should be counseled about potential post-treatment declines in QOL despite higher absolute QOL scores. Communicating these differences to patients will facilitate more appropriate treatment decision-making in men of all ages. Patient summary In this study we evaluated quality of life before and after treatment for localized prostate cancer in a diverse patient population. Declines in quality of life after treatment varied according to age and treatment. We conclude that counseling about quality of life will help patients of all ages to make more appropriate treatment decisions.

Objective To assess the ability of current nomograms to predict disease progression at repeat biopsy or at delayed radical prostatectomy (RP) in a prospectively accrued cohort of patients managed by active surveillance (AS).

Purpose

We describe the outcomes of patients with low risk localized prostate cancer who were upgraded on a surveillance biopsy while on active surveillance and evaluated whether delayed treatment was associated with adverse outcome.

Materials and methods

We included men in the study with lower risk disease managed initially with active surveillance and upgraded to Gleason score 3+4 or greater. Patient demographics and disease characteristics were compared. Kaplan-Meier curve was used to estimate the treatment-free probability stratified by initial upgrade (3+4 vs 4+3 or greater), Cox regression analysis was used to examine factors associated with treatment and multivariate logistic regression analysis was used to evaluate the factors associated with adverse outcome at surgery.

Results

The final cohort comprised 219 men, with 150 (68%) upgraded to 3+4 and 69 (32%) to 4+3 or greater. Median time to upgrade was 23 months (IQR 11-49). A total of 163 men (74%) sought treatment, the majority (69%) with radical prostatectomy. The treatment-free survival rate at 5 years was 22% for 3+4 and 10% for 4+3 or greater upgrade. Upgrade to 4+3 or greater, higher prostate specific antigen density at diagnosis and shorter time to initial upgrade were associated with treatment. At surgical pathology 34% of cancers were downgraded while 6% were upgraded. Cancer volume at initial upgrade was associated with adverse pathological outcome at surgery (OR 3.33, 95% CI 1.19-9.29, p=0.02).

Conclusions

After Gleason score upgrade most patients elected treatment with radical prostatectomy. Among men who deferred definitive intervention, few experienced additional upgrading. At radical prostatectomy only 6% of cases were upgraded further and only tumor volume at initial upgrade was significantly associated with adverse pathological outcome.

Background:Previous studies have found persistent overuse of imaging for clinical staging of men with low-risk prostate cancer. We aimed to determine imaging trends in three cohorts of men.Methods:We analyzed imaging trends of men with prostate cancer who were a part of Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) (1998-2006), were insured by Medicare (1998-2006), or privately insured (Ingenix database, 2002-2006). The rates of computed tomography (CT), magnetic resonance imaging (MRI) and bone scan (BS) were determined and time trends were analyzed by linear regression. For men in CaPSURE, demographic and clinical predictors of test use were explored using a multivariable regression model.Results:Since 1998, there was a significant downward trend in BS (16%) use in the CaPSURE cohort (N=5156). There were slight downward trends (2.4 and 1.7%, respectively) in the use of CT and MRI. Among 54 322 Medicare patients, BS, CT and MRI use increased by 2.1, 10.8 and 2.2% and among 16 161 privately insured patients, use increased by 7.9, 8.9 and 3.7%, respectively. In CaPSURE, the use of any imaging test was greater in men with higher-risk disease. In addition, type of insurance and treatment affected the use of imaging tests in this population.Conclusions:There is widespread misuse of imaging tests in men with low-risk prostate cancer, particularly for CT. These findings highlight the need for examination of factors that drive decision making with respect to imaging in this setting. © 2014 Macmillan Publishers Limited.

Background

The optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse is unknown.

Methods

We identified men with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE) study who would have been eligible (⩽ cT3aN0M0, primary radical prostatectomy or radiotherapy, PSA relapse as the only evidence of recurrence) for a randomised trial comparing 'immediate' versus 'deferred' ADT initiation. We emulated such trial by assigning patients to the 'immediate' strategy if they initiated ADT within 3 months of PSA relapse and to the 'deferred' strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time. We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting.

Results

Of 2096 eligible patients (median age 69, interquartile range 63-75 years), 88% were white, 35% had a Gleason score ⩾ 7, 69% were treated with radical prostatectomy and 31% received radiotherapy only as primary treatment. The mean time from primary treatment to PSA relapse was 37.4 (standard deviation [SD] 34.2) months. Mean follow-up from primary treatment was 91.4 (SD 48.4) months. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52-1.60), which would be translated into a similar 5-year survival (difference between groups: -2.0% (95% CI: -10.0 to 5.9%).

Conclusion

Our analysis suggests that prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression.

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell.