Utility of multiparametric magnetic resonance imaging in the risk stratification of men with Grade Group 1 prostate cancer on active surveillance.

OBJECTIVE: To assess if the adoption of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) has improved the identification of occult higher-grade prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively identified men from the Johns Hopkins AS registry enrolled since 2013 (year of mpMRI adoption) with Grade Group (GG) 1 PCa and who underwent a single mpMRI. Men in this group were dichotomised by the presence (n = 207) or absence (negative mpMRI, n = 225) of one or more lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of ≥ 3. Both groups were compared to a third cohort of men with GG1 PCa enrolled in AS prior to 2013 (pre-mpMRI era, n = 669). The risk of upgrading to GG ≥ 2 PCa on follow-up biopsies (performed with or without MRI targeting) was evaluated among the groups using survival analysis. RESULTS: Men in both mpMRI groups underwent a median (interquartile range [IQR]) of 2 (2-3) biopsies separated by a median (IQR) interval of 13 (12-16) months, whereas men in the pre-MRI era underwent a median (IQR) of 3 (2-5) biopsies, separated by a median (IQR) interval of 12 (12-14) months. The 2- and 4-year upgrade-free survival rates were 93% and 83%, 74% and 59%; and, 87% and 76% for the negative mpMRI, PI-RADS ≥ 3, and pre-mpMRI-era groups, respectively (P < 0.001). On multivariable analysis, both mpMRI groups had significantly different risk of upgrading compared to pre-mpMRI-era group (negative mpMRI group: hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.39-0.95, P = 0.03; PI-RADS ≥ 3 group: HR 1.96, 95% CI 1.36-2.82, P < 0.001). CONCLUSIONS: mpMRI improves the risk stratification of men on AS and should be used to aid enrolment and monitoring decisions.

Reclassification rates are higher among African American men than Caucasians on active surveillance.

OBJECTIVE: To evaluate the risk of reclassification on serial biopsy for Caucasian and African American (AA) men with very low-risk (VLR) prostate cancer enrolled in a large prospective active surveillance (AS) registry. METHODS: The Johns Hopkins AS registry is a prospective observational study that has enrolled 982 men since 1994. Including only men who met all National Comprehensive Cancer Network VLR criteria (clinical stage ≤T1, Gleason score ≤6, prostate-specific antigen [PSA] level <10 ng/mL, PSA density <0.15 ng/mL/cm(3), positive cores <3, percent cancer per core ≤50), we analyzed a cohort of 654 men (615 Caucasians and 39 AAs). The association of race with reclassification on serial biopsy was assessed with competing-risks regressions. RESULTS: AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy (36% vs 16%; adjusted P <.001). Adjusting for PSA level, prostate size, volume of cancer on biopsy, treatment year, and body mass index, AA race was an independent predictor of biopsy reclassification (subdistribution hazard ratio, 1.8; P = .003). Examining specific modes of reclassification, AA race was independently associated with reclassification by grade (subdistribution hazard ratio, 3.0; P = .002) but not by volume. CONCLUSION: AA men with VLR prostate cancer followed on AS are at significantly higher risk of grade reclassification compared with Caucasians. Therefore, if the goal of AS is to selectively monitor men with low-grade disease, AA men may require alternate selection criteria.

Magnetic resonance-invisible versus magnetic resonance-visible prostate cancer in active surveillance: a preliminary report on disease outcomes.

OBJECTIVE: To assess the association between magnetic resonance (MR) appearance of prostate cancer on a baseline multiparametric prostate (MP) MR imaging (MRI) and biopsy outcome in men with favorable-risk prostate cancer managed with active surveillance (AS). MATERIALS AND METHODS: Ninety-six consecutive men (mean age, 67.8 years) who had a baseline MP MRI within 1 year of AS enrollment were included in the study. MP MRI results were analyzed to identify men with MR-invisible tumor defined as no signal abnormality on T2-weighted images, no focal restricted diffusion, and no perfusion abnormality on dynamic contrast-enhanced images. Patients with (n = 84) or without (n = 12) MR-visible tumor were compared and the impact of MR-invisibility of tumor on the risk of adverse biopsy pathology based on the Epstein criteria was investigated with a median follow-up of 23 months. RESULTS: Adverse biopsy pathology occurred in 36.5% (35 of 96) of patients. There was no significant difference in the fulfillment of AS criteria at enrollment, prostate-specific antigen level or density, prostate volume, and number of biopsies (total or after MRI) between the 2 groups of patients. A total of 8.3% (1 of 12) of men with MR-invisible tumor had adverse biopsy pathology as compared with 40.5% (34 of 84) of men with MR-visible tumors. The MR-invisibility of tumor was associated with a lower risk of adverse biopsy pathology (crude relative risk = 0.35; 95% confidence interval, 0.10-1.25; prostate-specific antigen density-adjusted relative risk = 0.21; 95% confidence interval, 0.03-1.32). CONCLUSION: The MR-invisibility of tumor on MP MRI could be of prognostic significance in monitoring men in AS with potential benefit of tailoring the frequency of surveillance biopsies and reducing the number of unnecessary biopsies.

Health-related quality-of-life outcomes after anatomic retropubic radical prostatectomy in the phosphodiesterase type 5 ERA: impact of neurovascular bundle preservation.

OBJECTIVES: To examine the impact of neurovascular bundle preservation on longitudinal health-related quality-of-life (HRQOL) outcomes after anatomic radical retropubic prostatectomy (RP) using a validated questionnaire. METHODS: We examined patient-reported sexual and urinary HRQOL at baseline and at 3, 6, 12, and 24 months after RP using the University of California, Los Angeles, Prostate Cancer Index among 342 patients treated between 2001 and 2004 by a single surgeon. The time to return to baseline urinary and sexual function and bother were compared between men who underwent unilateral versus bilateral nerve-sparing RP using a Cox proportional hazards regression model. RESULTS: Of the 342 patients, 15 (5%), 69 (20%), and 258 (75%) had no, one, or both neurovascular bundles preserved, respectively. After adjustment for age and baseline sexual function, bilateral nerve sparing was associated with greater sexual function scores than unilateral nerve sparing at all points, although the differences only approached or reached significance at 3 (P = 0.06) and 6 (P = 0.04) months after RP. After adjustment for age and baseline sexual function, a trend was noted for an earlier return to baseline sexual function among men who underwent bilateral nerve-sparing RP (hazard ratio 1.67, 95% confidence interval 0.88 to 3.17, P = 0.12), although this did not reach significance. More than 90% of the men returned to their baseline urinary function and bother, regardless of nerve-sparing status. CONCLUSIONS: In the current study, bilateral nerve-sparing RP was associated with better postoperative sexual HRQOL scores than unilateral nerve-sparing RP, although in general the differences were slight.

Prediagnostic plasma vitamin C levels and the subsequent risk of prostate cancer.

OBJECTIVE: Antioxidants, such as vitamin C, are hypothesized to prevent prostate carcinogenesis by protecting the DNA from oxidative damage. We assessed whether higher prediagnostic plasma concentrations of vitamin C were associated with a lower risk of prostate cancer in a well-nourished cohort of men. METHODS: Plasma concentrations of ascorbic acid (vitamin C) were previously determined in blood specimens collected between 1984 and 1990 in men participating in the Baltimore Longitudinal Study of Aging. Total plasma ascorbic acid (L-ascorbic acid plus dehydro-L-ascorbic acid) levels were measured by using a modification of the 2,4-dinitrophenylhydrazine method. Among the 498 male participants with measured plasma vitamin C levels, 62 men were subsequently diagnosed with prostate cancer during their lifetime. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for prostate cancer. RESULTS: The median plasma concentration of vitamin C for the cohort was 1.17 mg/dL, which is in the normal to high range for older men. The age-adjusted relative risk of prostate cancer for the highest quartile (median = 1.47 mg/dL, range = 1.36-2.58) compared with the lowest quartile (median = 0.83 mg/dL, range = 0.15-0.98) of plasma vitamin C concentration was 1.31 (95% confidence interval 0.63 to 2.70, P for trend = 0.29). Adjustment for cigarette smoking status, body mass index, or plasma cholesterol concentration did not attenuate the results. CONCLUSIONS: This small but prospective study suggests that higher plasma vitamin C concentrations within the normal physiologic range are not associated with a lower risk of prostate cancer in well-nourished men.

Obesity does not adversely affect health-related quality-of-life outcomes after anatomic retropubic radical prostatectomy.

OBJECTIVES: To study the impact of obesity on the health-related quality-of-life (HRQOL) outcomes after radical prostatectomy (RP). METHODS: Patient-reported sexual and urinary HRQOL was assessed at baseline and 3, 6, 12, and 24 months after anatomic retropubic RP using the University of California, Los Angeles, Prostate Cancer Index among a cohort of 340 men. Linear regression analysis was used to compare the longitudinal HRQOL scores by body mass index (BMI) adjusting for age, baseline HRQOL, and nerve-sparing status (non-nerve sparing versus unilateral versus bilateral). RESULTS: At baseline, the sexual and urinary function and bother scores were similar between normal-weight (BMI less than 25 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), and obese (BMI 30 kg/m2 or greater) men. Obese men were as likely to undergo bilateral nerve-sparing surgery as men with a lower BMI. After adjustment for age, baseline HRQOL, and nerve-sparing status, no statistically significant differences were found in any HRQOL score at any point among the BMI groups, except for a lower urinary function score at 24 months among overweight men (P = 0.02). CONCLUSIONS: In a select group of men undergoing RP at a tertiary care referral center, BMI was, in general, unrelated to the baseline and longitudinal postoperative HRQOL scores. Obese men (BMI 30 to 35 kg/m2) should not be selectively discouraged against RP because of concerns about HRQOL. Additional studies are needed to assess the HRQOL outcomes among men with very high BMI values (greater than 35 kg/m2).

Nonsteroidal anti-inflammatory drugs and risk of prostate cancer in the Baltimore Longitudinal Study of Aging.

BACKGROUND: Laboratory and epidemiologic studies suggest that aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk of cancer, possibly via inhibition of the cyclooxygenase enzymes. We evaluated the association of aspirin and nonaspirin NSAIDs with subsequent prostate cancer in a prospective study. We also assessed whether use of these drugs influences serum prostate-specific antigen (PSA) concentration. METHODS: Participants were 1,244 male members of the Baltimore Longitudinal Study of Aging. Use of prescription and over-the-counter drugs was collected by questionnaire and interview at multiple study visits. One hundred forty-one prostate cancer cases diagnosed between 1980 and May 2004 were confirmed by medical record review. We used Cox proportional hazards regression to estimate the rate ratio (RR) of prostate cancer updating drug use over time and taking into account age and year. We used generalized estimating equations to calculate age-adjusted geometric mean PSA concentration by aspirin or nonaspirin NSAIDs use among 933 of the men without prostate cancer, for whom 3,749 PSA measurements in archived sera had been done previously. RESULTS: On 46.0% and 21.5% of the visits, current use of aspirin or nonaspirin NSAIDs (mostly ibuprofen) was reported, respectively. The RRs of prostate cancer comparing ever to never use were 0.76 [95% confidence interval (95% CI), 0.54-1.07] for aspirin, 0.79 (95% CI, 0.54-1.16) for nonaspirin NSAIDs, and 0.71 (95% CI, 0.49-1.02) for either medication. The association for ever use of either aspirin or nonaspirin NSAIDs was suggestively more pronounced in men <70 years (RR, 0.54; 95% CI, 0.27-1.03) than in men >/=70 years (RR, 0.78; 95% CI, 0.50-1.22; P(interaction) = 0.73). The RR for current use of either drug was attenuated relative to ever use. Mean PSA concentration did not differ between users and nonusers of either aspirin or nonaspirin NSAIDs (1.01 versus 0.98 ng/mL, P = 0.56). CONCLUSION: In this prospective study, men, in particular younger men, who had ever used aspirin or nonaspirin NSAIDs had a modest nonstatistically significant lower risk of prostate cancer. The modest inverse association was unlikely due to detection bias that might have resulted if anti-inflammatory drugs had influenced serum PSA concentration.

Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging.

OBJECTIVES: To examine the relationship of insulin, glucose, and anthropometry with the subsequent risk of prostate cancer. METHODS: The relative risk of prostate cancer by insulin, glucose, and anthropometric measures was evaluated in 823 male participants (87 patients with prostate cancer in 10,737 person-years of follow-up) of the Baltimore Longitudinal Study of Aging who had at least one fasting plasma insulin measurement, which was prediagnostic for those with prostate cancer. Age-adjusted and multivariate-adjusted relative risks were estimated from Cox proportional hazards regression models. RESULTS: Insulin concentrations were in the normal range (defined as less than 20 microU/mL) for 95.1% of participants. Fasting insulin and glucose levels were unrelated to prostate cancer risk in our overall analysis (P for trend = 0.56 and 0.45, respectively). The relative risk of prostate cancer for the second through fourth quartiles of the waist/hip ratio compared with the lowest quartile was 2.10, 1.96, and 2.06, respectively (P for trend = 0.32). Risk was unrelated to waist circumference and body mass index. CONCLUSIONS: The results of this study do not conclusively support positive associations of markers of insulin and glucose metabolism and obesity with prostate cancer. Additional larger prospective studies with repeated measure of these parameters are warranted to explore these associations further.

Association of energy intake with prostate cancer in a long-term aging study: Baltimore Longitudinal Study of Aging (United States).

OBJECTIVES: To examine the association of total energy intake and macronutrient contributors to energy with prostate cancer risk among men in the Baltimore Longitudinal Study of Aging. METHODS: In the Baltimore Longitudinal Study of Aging cohort, 444 men completed at least one food frequency questionnaire (FFQ). At their earliest FFQ completion, men were 45 to 92 years old. The total number of prostate cancer cases (n = 68) consisted of men who were diagnosed with cancer before their FFQ completion (n = 46) and those who were diagnosed after their FFQ completion (n = 22). Multiple logistic regression analysis was used to calculate the odds ratio of prostate cancer and its 95% confidence interval. RESULTS: Total energy intake was positively associated with prostate cancer. Compared with the lowest quintile of energy intake, the odds ratio for the highest quintile was 3.79 (95% confidence interval 1.52 to 9.48, P TREND = 0.002). Energy-adjusted intakes of protein, fat, and carbohydrates were not statistically significantly associated with prostate cancer risk. CONCLUSIONS: This analysis, in which we used current energy intake as a surrogate for past prediagnostic intake, suggests a higher risk of prostate cancer with increased energy intake.

Calcium intake and prostate cancer risk in a long-term aging study: the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To investigate the association between prostate cancer and calcium and other nutrients thought to influence the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D]. METHODS: We included in the analysis 454 male participants in the Baltimore Longitudinal Study of Aging who were 46 to 92 years old at the time of completion of a food frequency questionnaire. Among them, 69 men were diagnosed with prostate cancer during their lifetime. In 68% of the cases, the food frequency questionnaire was completed after the diagnosis of cancer. Multiple logistic regression analysis was used to calculate the odds ratio and 95% confidence interval of prostate cancer. RESULTS: The median calcium intake was 788 mg/day. The adjusted odds ratio of prostate cancer for the highest tertile compared with the lowest tertile of calcium intake was 0.92 (95% confidence interval 0.48 to 1.77; P(trend) = 0.89). Likewise, no significant trends were found for phosphorus, vitamin D, fructose, or animal protein intake. Dairy products, including milk, were not associated with an increased risk of prostate cancer. The adjusted odds ratio of prostate cancer was 1.26 (95% confidence interval 0.57 to 2.79; P(trend) = 0.73) for men with high dairy intakes compared with those with low dairy intakes. CONCLUSIONS: The results of this study suggest that calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer.