Evaluation of Apparent Diffusion Coefficient as a Predictor of Grade Reclassification in Men on Active Surveillance for Prostate Cancer.

OBJECTIVE: To evaluate the association between apparent diffusion coefficient (ADC) on initial multiparametric MRI (mpMRI) and biopsy grade reclassification (GR) to grade group (GG) ≥2 prostate cancer (CaP) in men on active surveillance (AS) with GG 1 CaP. METHODS: We retrospectively identified 242 AS patients with reported ADC values on their initial mpMRI. ADC value from the index lesion was assessed as an independent predictor of GR using a Cox model. To ease clinical interpretation, we used a log-rank test to establish an ADC cutoff of 1128 × 10-6 mm2/s for Kaplan-Meier analysis. RESULTS: Of the 242 men, 70 underwent GR following initial mpMRI, of which 26 (37%) had GR at the index lesion. There was no significant difference in the median interval between biopsies for men with and without GR (P >.9). Men with GR had significantly lower median ADC than those without GR (P = .01). In multivariable analysis adjusting for age, prostate-specific antigen density, and National Comprehensive Cancer Network risk group, a 100-unit decrease in ADC was associated with a 12% increase in the risk of GR (HR = 1.12, 95% CI: 1.01-1.22, P = .03). Two- and 4-year rates of freedom from GR were significantly lower for men with ADC <1128 × 10-6 mm2/s vs ADC ≥1128 × 10-6 mm2/s (62% and 42% vs 78% and 68%, respectively; P <.001). CONCLUSION: For AS patients, lower ADC on initial mpMRI index lesion is associated with increased risk of GR to GG ≥2 CaP and would be a useful component of multivariable risk prediction tools.

Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance.

PURPOSE: Age at prostate cancer diagnosis has been positively associated with prostate cancer specific mortality and in men on active surveillance with a higher risk of biopsy grade reclassification to Gleason score 3 + 4 or greater (Grade Group 2 or greater). However, to our knowledge the association between age and biopsy grade reclassification to an aggressive phenotype (Gleason score 4 + 3 or greater [Grade Group 3 or greater]) has not been explored. MATERIALS AND METHODS: From 1995 to 2016 we followed 1,625 men 41 to 81 years old with NCCN® (National Comprehensive Cancer Network®) very low (68%) or low (32%) risk prostate cancer on active surveillance. We determined the rate of biopsy grade reclassification to Grade Group 3 or greater. Competing risk analysis was applied to evaluate the association between age at enrollment and the risk of biopsy grade reclassification. Additionally, in men who underwent radical prostatectomy after biopsy grade reclassification we assessed the rate of radical prostatectomy grade reclassification (ie radical prostatectomy Grade Group greater than biopsy Grade Group). RESULTS: The 5-year incidence of biopsy grade reclassification to Grade Group 3 or greater was 4%, 7% and 14% in men younger than 60, 60 to 69 and 70 years old or older, respectively (p <0.001). On univariate analysis older age was associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.43, p <0.001). On multivariable analysis adjusting for year of diagnosis, race, prostate specific antigen density and cancer volume at diagnosis older age remained associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.19, p <0.001). In men who underwent radical prostatectomy after biopsy grade reclassification those who were older had a higher rate of radical prostatectomy grade reclassification (p <0.05). CONCLUSIONS: In men on active surveillance older age at diagnosis was positively associated with biopsy grade reclassification to Grade Group 3 or greater and radical prostatectomy grade reclassification. These observations imply that for many older men, active surveillance as opposed to watchful waiting remains a more appropriate management strategy.

Informational needs during active surveillance for prostate cancer: A qualitative study.

OBJECTIVE: To understand the informational needs during active surveillance (AS) for prostate cancer from the perspectives of patients and providers. METHODS: We conducted seven focus groups with 37 AS patients in two urban clinical settings, and 24 semi-structured interviews with a national sample of providers. Transcripts were analyzed using applied thematic analysis, and themes were organized using descriptive matrix analyses. RESULTS: We identified six themes related to informational needs during AS: 1) more information on prostate cancer (biopsy features, prognosis), 2) more information on active surveillance (difference from watchful waiting, testing protocol), 3) more information on alternative management options (complementary medicine, lifestyle modification), 4) greater variety of resources (multiple formats, targeting different audiences), 5) more social support and interaction, and 6) verified integrity of information (trusted, multidisciplinary and secure). CONCLUSIONS: Patients and providers described numerous drawbacks to existing prostate cancer resources and a variety of unmet needs including information on prognosis, AS testing protocols, and lifestyle modification. They also expressed a need for different types of resources, including interaction and unbiased information. PRACTICAL IMPLICATIONS: These results are useful to inform the design of future resources for men undergoing AS.

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.

Do environmental factors modify the genetic risk of prostate cancer?

BACKGROUND: Many SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown. METHODS: We evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥12 SNPs) and prostate cancer within environmental factor strata and tested for interaction. RESULTS: Men with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for ≥12 alleles was 2.06 [95% confidence interval (CI), 1.67-2.55] in nonusers and 0.99 (0.38-2.58) in users (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69-3.00) in nonusers and 1.70 (1.25-2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010). CONCLUSIONS: This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer. IMPACT: The effect of genetic factors on prostate cancer risk may vary by lifestyle interventions.

Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men.

PURPOSE: Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. MATERIALS AND METHODS: Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. RESULTS: Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm(3) (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm(3), p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). CONCLUSIONS: Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance.

African American men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them?

PURPOSE: Active surveillance (AS) is a treatment option for men with very low-risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low-risk PCa, we evaluated oncologic outcomes of AA men with very low-risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP). PATIENTS AND METHODS: We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low-risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features. RESULTS: AA men with very low-risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03). CONCLUSION: AA men with very low-risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low-risk PCa should be counseled about increased oncologic risk when deciding among their disease management options.

Subclassification of clinical stage T1 prostate cancer: impact on biochemical recurrence following radical prostatectomy.

PURPOSE: We investigated biochemical outcomes following radical prostatectomy across subclassifications of clinical stage T1 prostate cancer. MATERIAL AND METHODS: Of 8,658 men who underwent radical prostatectomy for clinical stage T1 prostate cancer 85, 156 and 8,417 had clinical stage T1a, T1b and T1c disease, respectively. Age, race, prostate specific antigen, year of surgery and preoperative Gleason scores were compared across clinical stage T1 subcategories. Time to prostate specific antigen recurrence was compared among groups using Kaplan-Meier and Cox hazards modeling. RESULTS: Patients with clinical stage T1a prostate cancer had more favorable postoperative pathological features, including lower prostatectomy Gleason scores (p <0.001), rates of extraprostatic extension (p <0.001), lymph node invasion (p <0.001) and positive surgical margins (p = 0.006). Patients with T1a cancer also showed significantly lower rates of biochemical recurrence on Kaplan-Meier analysis than men with T1b and T1c disease (log rank 0.006). Cox regression analysis adjusted for known predictors of biochemical recurrence demonstrated that clinical tumor stage in the subgroup of patients with T1 disease was not an independent predictor of biochemical recurrence (p = 0.321). CONCLUSIONS: Men with clinical stage T1a prostate cancer who undergo radical prostatectomy have significantly lower biochemical recurrence rates than men with stage T1b or T1c disease. However, subclassification of tumors in this group of patients was not an independent prognostic factor for biochemical recurrence after accounting for preoperative variables, including prostate specific antigen and Gleason score.

Efficacy of periprostatic local anesthetic for prostate biopsy analgesia: a meta-analysis.

OBJECTIVES: To perform a meta-analysis of available randomized trials investigating the analgesic efficacy of periprostatic block with local anesthetic. METHODS: The National Library of Medicine's PubMed database was searched for the time period 1966 to August 16, 2005 for all relevant articles. Inclusion criteria included subjects undergoing prostate biopsy, trials that were randomized with one arm of the randomization using local anesthetic for periprostatic block before prostate biopsy, and where the assessment of biopsy pain was measured and available in a form compatible for statistical analysis in our meta-analysis. RESULTS: Our search resulted in 107 abstracts, of which a total of 16 articles met all inclusion criteria. There were 660 subjects who received local anesthetics for a periprostatic block and 616 subjects who did not. The weighted mean difference between the groups indicates that subjects receiving local anesthetic periprostatic block would have a statistically lower pain score compared with those who did not (weighted mean difference in visual analogue pain of -1.66 [95% confidence interval -2.03 to -1.29]). CONCLUSIONS: Our meta-analysis suggests that periprostatic block with local anesthetic for prostate biopsy might result in significantly lower levels of pain during the biopsy procedure. Because periprostatic block with local anesthetic is relatively easy to administer and does not seem to be associated with increased morbidity, clinicians performing prostate biopsies should consider using this technique on a routine basis.

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.