Introduction and Objectives The clinical significance of ductal prostatic carcinoma has not been well defined. We utilized a population-based cancer registry to identify a large group of ductal carcinoma cases to characterize the impact of the ductal subtype on the presentation and survival of men with prostate cancer. Methods A national cancer registry was used to identify incident cases of ductal and acinar adenocarcinomas from 1996–2006. Clinicopathologic variables were analyzed and Cox multivariate survival analysis performed. PSA values were available for the years 2004–2006, and these were used to assess for differences in Gleason grade and serum PSA levels between ductal and acinar cancers at the time of diagnosis. Results A total of 442,881 acinar cases and 371 ductal cases were identified. Ductal cases were more likely to present with distant disease (12% vs. 4%, p<0.001) and to be poorly differentiated (50% vs. 32%; p<0.001). Ductal histology was associated with a 30% lowering of the geometric mean PSA (adjusted coeff.=0.7, 95% CI 0.6–0.8) and a more than two-fold increased odds of having a PSA<4.0 ng/ml (OR 2.4, 95% CI 1.4–4.0) independent of other clinicopathologic variables. For those with non-distant disease at diagnosis, ductal histology was associated with a 2.4-fold (CI 1.5–3.8) increased disease-specific mortality. Conclusions In the largest series of this histologic subtype, ductal cancers were more likely to present with advanced stage cancer and a lower PSA, suggesting that timely detection of the disease is a significant challenge. In addition, those with loco regional disease were more likely to die of their disease.

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The COBRA score offers a straightforward, validated risk-stratification tool that incorporates the relative contribution of tumor stage and lymph node involvement to patient prognosis after cystectomy for UCB. Cancer 2017;123:4574-4582. © 2017 American Cancer Society.

Qualitative and quantitative bone features were determined in nondecalcified and decalcified bone from 20 predetermined bone sites in each of 44 patients who died with castration resistant prostate cancer (CRPC), some of which received bisphosphonate treatment (BP) in addition to androgen deprivation therapy (ADT). Thirty nine of the 44 patients (89%) had evidence of bone metastases. By histomorphometric analysis, these bone metastases were associated with a range of bone responses from osteoblastic to osteolytic with a wide spectrum of bone responses often seen within an individual patient. Overall, the average bone volume/tissue volume (BV/TV) was 25.7% confirming the characteristic association of an osteoblastic response to prostate cancer bone metastasis when compared to the normal age-matched weighted mean BV/TV of 14.7%. The observed new bone formation was essentially woven bone and this was a localized event. In comparing BV/TV at metastatic sites between patients who had received BP treatment and those that had not, there was a significant difference (28.6% vs 19.3%, respectively). At bone sites that were not invaded by tumor, the average BV/TV was 10.1% indicating significant bone loss due to ADT that was not improved (11%) in those patients who had received BPs. Surprisingly there was no significant difference in the number of osteoclasts present at the metastatic sites between patients treated or not treated with BPs but in bone sites where the patient had been treated with BPs, giant osteoclasts were observed. Overall, 873 paraffin embedded specimens and 661 methylmethacrylate embedded specimens were analyzed. Our results indicate that in CRPC patients, ADT induces serious bone loss even in patients treated with BP. Furthermore, in this cohort of patients, BP treatment increased BV and did not decrease the number of osteoclasts in prostate cancer bone metastases compared to bone metastases from patients who did not receive BP.

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Purpose of reviewActive surveillance is a management strategy for early-stage prostate cancer designed to balance early detection of aggressive disease and overtreatment of indolent disease. We evaluate recently reported outcomes and discuss the potentially most important endpoints for such an approach. Recent findingsThe past 2 years have seen the publication of two trials of watchful waiting versus immediate treatment and updates of multiple active surveillance cohorts for men with early-stage prostate cancer. The watchful waiting trials demonstrated a small potential mortality benefit to immediate treatment when applied to all risk levels (6% absolute difference at 15 years), emphasizing the importance of a risk-adapted strategy. In reported active surveillance cohorts, prostate cancer death and metastasis remain rare events. Intermediate outcomes such as progression to treatment and upgrading/upstaging on final disease appear consistent among cohorts, but must be interpreted with caution when compared with historical controls of immediate treatment because of potential selection bias. SummaryThe safety of active surveillance has been reinforced by recent reports. Accumulation of additional data on men with intermediate risk cancer and development and validation of new biomarkers of risk will allow refined and, likely, expanded use of this approach.

BackgroundThe ability to interrogate circulating tumor cells (CTC) and disseminated tumor cells (DTC) is restricted by the small number detected and isolated (typically <10). To determine if a commercially available technology could provide a transcriptomic profile of a single prostate cancer (PCa) cell, we clonally selected and cultured a single passage of cell cycle synchronized C4-2B PCa cells. Ten sets of single, 5-, or 10-cells were isolated using a micromanipulator under direct visualization with an inverted microscope. Additionally, two groups of 10 individual DTC, each isolated from bone marrow of 2 patients with metastatic PCa were obtained. RNA was amplified using the WT-Ovation™ One-Direct Amplification System. The amplified material was hybridized on a 44K Whole Human Gene Expression Microarray. A high stringency threshold, a mean Alexa Fluor® 3 signal intensity above 300, was used for gene detection. Relative expression levels were validated for select genes using real-time PCR (RT-qPCR).ResultsUsing this approach, 22,410, 20,423, and 17,009 probes were positive on the arrays from 10-cell pools, 5-cell pools, and single-cells, respectively. The sensitivity and specificity of gene detection on the single-cell analyses were 0.739 and 0.972 respectively when compared to 10-cell pools, and 0.814 and 0.979 respectively when compared to 5-cell pools, demonstrating a low false positive rate. Among 10,000 randomly selected pairs of genes, the Pearson correlation coefficient was 0.875 between the single-cell and 5-cell pools and 0.783 between the single-cell and 10-cell pools. As expected, abundant transcripts in the 5- and 10-cell samples were detected by RT-qPCR in the single-cell isolates, while lower abundance messages were not. Using the same stringency, 16,039 probes were positive on the patient single-cell arrays. Cluster analysis showed that all 10 DTC grouped together within each patient.ConclusionsA transcriptomic profile can be reliably obtained from a single cell using commercially available technology. As expected, fewer amplified genes are detected from a single-cell sample than from pooled-cell samples, however this method can be used to reliably obtain a transcriptomic profile from DTC isolated from the bone marrow of patients with PCa.

Objectives Cigarette smoking is a known risk factor for urothelial carcinoma (UC) of the bladder. However, the persistence of an increased risk for UC following smoking cessation is not well established. We assessed the risk of UC among former smokers using a recent, prospective cohort with a high proportion of former smokers. Materials and methods Study participants were members of the VITamins And Lifestyle cohort (VITAL), a group of 77,719 men and women between the ages of 50 and 76 years from western Washington State. Smoking history and other risk factors were obtained at the time of recruitment. The primary outcome was a new diagnosis of UC (n = 385), as determined through linkage to a population-based cancer registry. Results and limitations The cohort included 8% current and 44% former smokers, and among the UC cases, 15% were current and 60% former smokers. Both the current and former smoker had an increased risk of UC compared with never smokers (hazard ratio [HRs]: 3.81; 95% confidence intervals [CI] 2.71–5.35 and 2.0; 95% CI 1.55–2.58, respectively). Among former smokers, the risk of UC increased with the pack-years smoked and decreased with the years since quitting. When both the measures of smoking were considered together, the risk of UC was similar for long-term quitters and recent quitters for a given level of pack-years. For example, for those with pack-years of 22.5–37.5, the HR of UC was 1.91 (95% CI 1.17–3.11) for the distant quitters (≥23.5 y before baseline) and HR = 1.92 (95% CI 1.26–2.94) among the recent quitters. Limitations include the small number of cases at the extremes of smoking history and errors in self-reported smoking history. Conclusions The risk of bladder cancer in former smokers remains elevated >32 years after quitting, even among those with moderate smoking histories. This argues that a history of smoking confers a lifelong increased risk of UC.