Showing papers in "Prostate Cancer and Prostatic Diseases in 2015"
TL;DR: In human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.
Abstract: Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation—constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.
152 citations
TL;DR: A novel molecular signature derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with ‘gray zone’ serum PSA levels.
Abstract: A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result
135 citations
TL;DR: The activity of enzalutamide is blunted after abiraterone, after docetaxel, and still more after both, suggesting subsets of overlapping and distinct mechanisms of resistance.
Abstract: Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel
80 citations
TL;DR: The characteristics of prostate cancer CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies are explored.
Abstract: Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies.
67 citations
TL;DR: MRI-targeted biopsies detected significantly more anteriorly located significant prostate cancer (sPC) compared with SBs in the repeat-biopsy setting, and the more cost-efficient bpMRI was statistically not inferior to mpMRI in sPC detection in TZ/AFMS.
Abstract: Improved detection of anterior fibromuscular stroma and transition zone prostate cancer using biparametric and multiparametric MRI with MRI-targeted biopsy and MRI-US fusion guidance
64 citations
TL;DR: DNA hypomethylation was associated with PCa development and progression, however, due to the heterogeneity and small sample sizes of the included studies, along with the possibility of publication bias, this association requires additional assessment.
Abstract: The role of global DNA methylation in prostate cancer (PCa) remains largely unknown. Our aim was to summarize evidence on the role of global DNA hypomethylation in PCa development and progression. We searched PubMed through December 2013 for all studies containing information on global methylation levels in PCa tissue and at least one non-tumor comparison tissue and/or studies reporting association between global methylation levels in PCa tissue and survival, disease recurrence or at least one clinicopathological prognostic factor. We summarized results using non-parametric comparisons and P-value summary methods. We included 15 studies in the review: 6 studies with both diagnostic and prognostic information, 5 studies with only diagnostic information and 4 studies with only prognostic information. Quantitative meta-analysis was not possible because of the large heterogeneity in molecular techniques, types of tissues analyzed, aims and study designs. Summary statistical tests showed association of DNA hypomethylation with PCa diagnosis (P 0.1 except for the weighted Z-test, P=0.05). DNA hypomethylation was associated with PCa development and progression. However, due to the heterogeneity and small sample sizes of the included studies, along with the possibility of publication bias, this association requires additional assessment.
62 citations
TL;DR: Systematic review revealed mixed findings on metformin use and the risk of CRPC, and randomized trials should be designed to assess the efficacy of met formin use in prostate cancer.
Abstract: Conflicting evidence exists regarding the beneficial effects of metformin in prostate cancer. To determine the association between metformin and clinical outcomes in prostate cancer using systematic review and meta-analysis. Original articles published in English until third week of July, 2014 were searched in electronic databases (Medline-Ovid, Scopus, The Cochrane Library, Web of Science, ProQuest) for studies on metformin use in prostate cancer. The clinical outcomes assessed were: development of biochemical recurrence, metastases or castration-resistant metastatic cancer, all-cause and prostate cancer-specific mortality. Meta-analysis was performed to calculate the pooled hazard ratio (pHR) and their 95% confidence interval (95% CI). Heterogeneity between the studies was examined using I2 statistics. Sensitivity analysis was conducted to assess the robustness of findings and publication bias was assessed by the Egger’s regression asymmetry test and contour plot. Out of 230 retrieved citations, eight retrospective cohort studies and one nested-case-control study met the inclusion criteria. Metformin use was marginally associated with reduction in the risk of biochemical recurrence (pHR: 0.82, 95% CI: 0.67, 1.01, P-value=0.06, I2=25%, five studies). Metformin use was not significantly associated with metastases (pHR: 0.59, 95% 0.30–1.18, P-value=0.14, I2=74%, three studies), all-cause mortality (pHR: 0.86; 95% CI, 0.67, 1.10, P-value=0.23, I2: 73%, six studies) and prostate cancer-specific mortality (pHR: 0.76, 95% CI: 0.43, 1.33, P-value = 0.33, I2=60%, four studies). Pooled estimates for all outcomes varied in sensitivity analysis by diabetes status and primary treatment of prostate cancer. Systematic review revealed mixed findings on metformin use and the risk of CRPC. Metformin may reduce the risk of biochemical recurrence in prostate cancer. Given the potential of selection bias in the observational studies, randomized trials should be designed to assess the efficacy of metformin use in prostate cancer.
56 citations
TL;DR: mp-MRI can detect radiorecurrent prostate cancer and the optimal examination included T2-weighted imaging and high b-value DWI; adding ADC maps and DCE imaging did not significantly improve the diagnostic accuracy.
Abstract: Multiparametric magnetic resonance imaging (mp-MRI) is increasingly advocated for prostate cancer detection. There are limited reports of its use in the setting of radiorecurrent disease. Our aim was to assess mp-MRI for detection of radiorecurrent prostate cancer and examine the added value of its functional sequences. Thirty-seven men with mean age of 69.7 (interquartile range, 66–74) with biochemical failure after external beam radiotherapy underwent mp-MRI (T2-weighted, high b-value, multi-b-value apparent diffusion coefficient (ADC) and dynamic contrast-enhanced (DCE) imaging); then transperineal systematic template prostate mapping (TPM) biopsy. Using a locked sequential read paradigm (with the sequence order above), two experienced radiologists independently reported mp-MRI studies using score 1–5. Radiologist scores were matched with TPM histopathology at the hemigland level (n=74). Accuracy statistics were derived for each reader. Interobserver agreement was evaluated using kappa statistics. Receiver–operator characteristic area under curve (AUC) for readers 1 and 2 increased from 0.67 (95% confidence interval (CI), 0.55–0.80) to 0.80 (95% CI, 0.69–0.91) and from 0.67 (95% CI, 0.55–0.80) to 0.84 (95% CI, 0.76–0.93), respectively, between T2-weighted imaging alone and full mp-MRI reads. Addition of ADC maps and DCE imaging to the examination did not significantly improve AUC for either reader (P=0.08 and 0.47 after adding ADC, P=0.90 and 0.27 after adding DCE imaging) compared with T2+high b-value review. Inter-reader agreement increased from k=0.39 to k=0.65 between T2 and full mp-MRI review. mp-MRI can detect radiorecurrent prostate cancer. The optimal examination included T2-weighted imaging and high b-value DWI; adding ADC maps and DCE imaging did not significantly improve the diagnostic accuracy.
54 citations
TL;DR: The results show that the use of acupuncture in treatment of men with CP/CPPS symptoms resulted in a significant decrease in total NIH-CPSI scores.
Abstract: Acupuncture relieves symptoms in chronic prostatitis/chronic pelvic pain syndrome: a randomized, sham-controlled trial
52 citations
TL;DR: MRI, especially multiparametric (MP)-MRI, has a moderate diagnostic accuracy as a significant predictor of disease reclassification among AS candidates and the high NPV and specificity for the prediction of biopsy re classification upon clinical follow-up suggest that negative prostate MRI findings may support a patient remaining under AS.
Abstract: Active surveillance (AS) is an increasingly important attempt to avoid overtreatment of patients who harbor clinically insignificant disease while offering curative treatment to those in whom disease is reclassified as higher risk after an observation period and repeat biopsy We aim to evaluate the diagnostic performance of magnetic resonance imaging (MRI) in predicting upgrading on confirmatory biopsy in men with low-risk prostate cancer (PCa) on AS We searched the PubMed for pertinent studies up to November 2014 We used standard methods recommended for meta-analyses of diagnostic test evaluations The analysis was based on a summary receiver operating characteristic (SROC) curve Meta-regression analysis was used to assess the effects of some confounding factors on the results of the meta-analysis The potential presence of publication bias was tested using the Deeks’ funnel plots Seven studies provided the diagnostic data on MRI and AS of PCa, comprising 1028 patients The pooled estimates of MRI on disease reclassification among AS candidates were as follows: sensitivity, 069 (95% confidence interval (CI), 044–086); specificity, 078 (95% CI, 053–091); positive likelihood ratio, 31 (95% CI, 16–60); negative likelihood ratio, 040 (95% CI, 023–070); and diagnostic odds ratio, 8 (95% CI, 4–16) The P-value for heterogeneity was 10 mm lesion may suggest an increased risk for disease progression
50 citations
TL;DR: Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.
Abstract: The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P 0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.
TL;DR: The use of laparoscopic-assisted prostatectomy increased from 1% in 2002 to 41% in 2006 in the privately insured i3 database while remaining stable at 12% in the Medicare population as discussed by the authors.
Abstract: Several treatment options for clinically localized prostate cancer currently exist under the established guidelines. We aim to assess nationally representative trends in treatment over time and determine potential geographic variation using two large national claims registries. Men with prostate cancer insured by Medicare (1998–2006) or a private insurer (Ingenix database, 2002–2006) were identified using International Classification of Diseases-9 and Current Procedural Terminology-4 codes. Geographic variation and trends in the type of treatment utilized over time were assessed. Geographic data were mapped using the GeoCommons online mapping platform. Predictors of any treatment were determined using a hierarchical generalized linear mixed model using the logit link function. The use of radical prostatectomy increased, 33–48%, in the privately insured i3 database while remaining stable at 12% in the Medicare population. There was a rapid uptake in the use of newer technologies over time in both the Medicare and i3 cohorts. The use of laparoscopic-assisted prostatectomy increased from 1% in 2002 to 41% in 2006 in i3 patients, whereas the incidence increased from 3% in 2002 to 35% in 2006 for Medicare patients. The use of neoadjuvant/adjuvant androgen deprivation therapy was lower in the i3 cohort and has decreased over time in both i3 and Medicare. Physician density had an impact on the type of primary treatment received in the New England region; however, this trend was not seen in the western or southern regions of the United States. Using two large national claims registries, we have demonstrated trends over time and substantial geographic variation in the type of primary treatment used for localized prostate cancer. Specifically, there has been a large increase in the use of newer technologies (that is, laparoscopic-assisted prostatectomy and intensity-modulated radiation therapy). These results elucidate the need for improved data collection on prostate cancer treatment outcomes to reduce unwarranted variation in care.
TL;DR: The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality and supports adjunctive therapies that can augment cell death pathways.
Abstract: It is now recognized that the tumor microenvironment creates a protective neo-tissue that isolates the tumor from the various defense strategies of the body. Evidence demonstrates that, with successive therapeutic attempts, cancer cells acquire resistance to individual treatment modalities. For example, exposure to cytotoxic drugs results in the survival of approximately 20-30% of the cancer cells as only dividing cells succumb to each toxic exposure. With follow-up treatments, each additional dose results in tumor-associated fibroblasts secreting surface-protective proteins, which enhance cancer cell resistance. Similar outcomes are reported following radiotherapy. These defensive strategies are indicative of evolved capabilities of cancer to assure successful tumor growth through well-established anti-tumor-protective adaptations. As such, successful cancer management requires the activation of multiple cellular 'kill switches' to prevent initiation of diverse protective adaptations. Thermal therapies are unique treatment modalities typically applied as monotherapies (without repetition) thereby denying cancer cells the opportunity to express defensive mutations. Further, the destructive mechanisms of action involved with cryoablation (CA) include both physical and molecular insults resulting in the disruption of multiple defensive strategies that are not cell cycle dependent and adds a damaging structural (physical) element. This review discusses the application and clinical outcomes of CA with an emphasis on the mechanisms of cell death induced by structural, metabolic, vascular and immune processes. The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality. Our understanding of these mechanisms now supports adjunctive therapies that can augment cell death pathways.
TL;DR: Proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity and proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer are discussed.
Abstract: Beneficial effects of physical activity have been illustrated in numerous aspects of health. With the increasing incidence of prostate cancer and changes in physical activity of men, understanding the link between the two has important implications for changing this cancer burden. Both positive and negative associations between physical activity and prostate cancer have been previously demonstrated in observational epidemiological studies. Elucidating the biological mechanisms would lead to a better understanding of how physical activity influences the progression of prostate cancer. This review was undertaken to: (1) identify evidence in literature that demonstrates the effects of physical activity on skeletal muscle secretomes, (2) indicate the plausible signaling pathways these proteins might activate, and (3) identify evidence in literature that demonstrates the roles of the signaling pathways in prostate cancer progression and regression. We also discuss proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer. We discuss proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity. We further identify future directions for research, including a better understanding of the biological mechanisms, the need to standardize physical activity and identify mechanistic end points of physical activity that can then be correlated with outcomes.
TL;DR: A systematic review and subsequent meta-analysis has shown superiority of α1-adrenergic receptor blockers over placebo in achieving successful voiding in patients with AUR and recommend use ofα1- adrenergic receptors before TWOC and discourage emergency operative management.
Abstract: Acute urinary retention (AUR) is a common urological emergency. In this article, we review the current literature and present a structured summary in management of AUR. A systematic review was conducted using the keywords 'acute AND retention AND urin*' within the title in search engines including Medline, EMBASE and EBM Review. The obtained literature was manually reviewed by the primary author (PDY) and was further refined by confining the subject to management of AUR. Exclusion criteria included paediatric and female population studies, case reports, reviews, surveys, economical assessment and articles on AUR in prostate cancer and post-operative patients. Total of 54 articles met our inclusion and exclusion criteria. The trial without catheter (TWOC) post-immediate catheterisation is widely practiced although there remains a significant variability in terms of type and duration of catheterisation required, use of concurrent medical therapy or post-catheterisation management. Our systematic review and subsequent meta-analysis has shown superiority of α1-adrenergic receptor blockers over placebo in achieving successful voiding in patients with AUR. Suprapubic catheter (SPC) is an alternative to urethral catheterisation (indwelling catheter (IDC)) and may provide several advantages. Clean intermittent self-catheterisation may be a safe and useful option for patients with AUR until their definitive management. The overall long-term outcome of in-and-out catheterisation remains promising in selected patients. Surgery is an end point in patients with unsuccessful TWOC as well as in those with significant lower urinary tract symptoms post-successful TWOC. We recommend use of α1-adrenergic receptor blockers before TWOC and discourage emergency operative management. Use of SPC over IDC in AUR is debatable. Duration of catheterisation is controversial but <3 days is a safe option in avoiding catheterisation-related complications. Although TURP remains the current gold standard, there has been an emergence of newer operative management utilising laser techniques.
TL;DR: Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen.
Abstract: To compare histological feature of prostate cancer (PCa) according androgenic status in patients who underwent radical prostatectomy (RP). Between March 2007 and September 2013, we prospectively analysed 937 patients who were referred to our centre for RP. Clinical, pathological and biological data have been prospectively collected. Preoperative total testosterone (TT) and bioavailable testosterone (BT) serum determinations were carried out. The threshold for low serum testosterone was set at TT<3 ng/ml. Preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern were determined in prostate biopsies and in prostate tissue specimens, crosschecked by two uro-pathologists. Nine hundred and thirty-seven consecutive patients were included. In all, 14.9% patients had low TT in the population. An exact match between biopsy and prostate specimens in GS grading was observed for 50.6% patients (n=474). Also, 40.9% of all patients were upgraded (n=383): 45.3% (n=63) in low serum testosterone patients and 40.1% (n=320) in normal serum testosterone patients. For prostate specimens, the proportion of patients with predominant Gleason pattern 4 was higher in patients with low TT compared with normal TT (41.7% vs 29.1%, P=0.0029). In all, 20.1% were upgraded from predominant Gleason pattern 3 on biopsies specimen to predominant Gleason 4 pattern on the prostate specimen in patients with low TT, whereas 11.6% were upgraded for normal TT patients (P=0.002). Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen. This observation should be taken into account in localised PCa management, especially for active surveillance or when a nerve-sparing approach is considered.
TL;DR: The combination of statins and metformin in men undergoing RP for prostate cancer (PCa) may be associated with a lower BCR risk than would be predicted based on the independent effects of both medications.
Abstract: Synergism between metformin and statins in modifying the risk of biochemical recurrence following radical prostatectomy in men with diabetes
TL;DR: It is concluded that the novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging and further translational studies of prostate R SI-MRI in the diagnosis and staging of PCa are indicated.
Abstract: Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension
Johns Hopkins University1, Amasya University2, Washington University in St. Louis3, Fred Hutchinson Cancer Research Center4, University of Texas at San Antonio5, University of California, San Diego6, University of Colorado Denver7, National Institutes of Health8, Johns Hopkins University School of Medicine9
TL;DR: In men without clinical suspicion of prostate cancer, greater overall inflammation, luminal and intraepithelial acute inflammation and stromal and intraepsithelial chronic inflammation were associated with higher serum PSA.
Abstract: Intraprostatic inflammation is positively associated with serum PSA in men with PSA −1 , normal DRE and negative for prostate cancer
TL;DR: LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks, and no clinically meaningful changes in laboratory tests were observed.
Abstract: Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy
TL;DR: The inclusion of Gs=3+4 in patients suitable to AS does not enhance the risk of unfavourable disease after radical prostatectomy, and additional factors such as number of cores taken and the presence of ASAP should be considered in Patients suitable for AS.
Abstract: To assess whether the addition of clinical Gleason score (Gs) 3+4 to the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria affects pathologic results in patients who are potentially suitable for active surveillance (AS) and to identify possible clinical predictors of unfavourable outcome. Three hundred and twenty-nine men who underwent radical prostatectomy with complete clinical and follow-up data and who would have fulfilled the inclusion criteria of the PRIAS protocol at the time of biopsy except for the addition of biopsy Gs=3+4 and with at least 10 cores taken have been evaluated. One experienced genitourinary pathologist selected those with real Gs=3+3 and 3+4 in only one core according to the 2005 International Society of Urological Pathology criteria. The primary end point was the proportion of unfavourable outcome (nonorgan confined disease or Gs⩾4+3). Logistic regressions explored the association between preoperative characteristics and the primary end point. Two hundred and four patients were evaluated and 46 (22.5%) patients harboured unfavourable disease at final pathology. After a median follow-up of 73.5 months, there was no cancer-specific death, and 4 (2.0%) patients had biochemical relapse. There were no significant differences in terms of high Gs, locally advanced disease, unfavourable disease and biochemical relapse-free survival among patients with clinical Gs=3+3 vs Gs=3+4. At multivariable analysis, the presence of atypical small acinar proliferation (ASAP) and lower number of core taken were independently associated with a higher risk of unfavourable disease. The inclusion of Gs=3+4 in patients suitable to AS does not enhance the risk of unfavourable disease after radical prostatectomy. Additional factors such as number of cores taken and the presence of ASAP should be considered in patients suitable for AS.
TL;DR: The overall rate of intermediate- and high-grade prostate cancer found on repeat biopsy for ASAP is low and repeatBiopsy of men diagnosed with ASAP remains prudent.
Abstract: Rate of Gleason 7 or higher prostate cancer on repeat biopsy after a diagnosis of atypical small acinar proliferation
TL;DR: No significant differences in tumor burden, treatment choice or survival outcomes between African Americans and Caucasians cared for in the equal-access VA Healthcare setting are found.
Abstract: African-American men with prostate cancer typically have higher tumor risk at diagnosis, lower rates of surgical treatment and poorer cancer-specific survival compared with Caucasians. Receipt of care within the Veterans Affairs (VA) healthcare system may reduce barriers that influence these disparities. We sampled 1258 men with nonmetastatic prostate cancer diagnosed at the Greater Los Angeles and Long Beach VA Medical Centers between 1998 and 2004. We compared African Americans and Caucasians with respect to tumor characteristics using ordinal logistic regression, treatment choice across substrata of tumor risk using logistic regression, and cancer-specific and other-cause mortality using competing risks regression analysis. Multivariate ordinal logistic regression revealed no significant differences in odds of higher tumor risk (odds ratio (OR) 1.22, 95% confidence interval (CI) 0.98–1.53, P=0.08), Gleason score (OR 0.90, 95% CI 0.7–1.16, P=0.4) or clinical stage (OR 1.04, 95% CI 0.79–1.38, P=0.8) for African Americans compared with Caucasians. African-American men had similar odds of aggressive treatment as did Caucasians for low-risk (OR 0.92, 95% CI 0.57–1.53, P=0.8), intermediate-risk (OR 0.75, 95% CI 0.44–1.26, P=0.3) and high-risk disease (OR 0.87, 95% CI 0.52–1.44, P=0.6). In competing risks regression analysis, African Americans had a lower but nonsignificant hazard of cancer-specific mortality compared with Caucasians (sub-hazard ratio 0.6, 95% CI 0.28–1.26, P=0.2) and nearly identical risk of other-cause mortality (sub-hazard ratio 0.98, 95% CI 0.78–1.22, P=0.8). We found no significant differences in tumor burden, treatment choice or survival outcomes between African Americans and Caucasians cared for in the equal-access VA Healthcare setting.
TL;DR: Combining PSA levels and kinetics may help select patients with CRPC for bone scans and develop tables to predict the risk of positive bone scans by PSA and PSADT.
Abstract: To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort. Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients’ demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations. A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2–6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8–10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5–14.9, 15–49.9 and ⩾50 ng ml−1, respectively (P-trend <0.001). Men with PSADT ⩾15, 9–14.9, 3–8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan. PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans.
TL;DR: The results suggest that CTCs may be indicative of disseminated disease and assessment of C TCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments.
Abstract: The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy
TL;DR: Caution must be exercised when interpreting T1- and T2-weighted imaging early post biopsy, whereas ADC images are more likely to maintain clinical efficacy, whereas PZ and TZ ADC is not significantly altered as early as 1 month postBiopsy.
Abstract: To determine the evolution of prostatic multi-parametric magnetic resonance imaging (mp-MRI) signal following transrectal ultrasound (TRUS)-guided biopsy. Local ethical permission and informed written consent was obtained from all the participants (n=14, aged 43–69, mean 64 years). Patients with a clinical suspicion of prostate cancer (PSA range 2.2–11.7, mean 6.2) and a negative (PIRAD 1–2/5) pre-biopsy mp-MRI (pre-contrast T1, T2, diffusion-weighted and dynamic-contrast-enhanced MRI) who underwent 10-core TRUS-guided biopsy were recruited for additional mp-MRI examinations performed at 1, 2 and 6 months post biopsy. We quantified mp-MRI peripheral zone (PZ) and transition zone (TZ) normalized T2 signal intensity (nT2-SI); T1 relaxation time (T10); diffusion-weighted MRI, apparent diffusion coefficient (ADC); dynamic contrast-enhanced MRI, maximum enhancement (ME); slope of enhancement (SoE) and area-under-the-contrast-enhancement-curve at 120 s (AUC120). Significant changes in mp-MRI parameters were identified by analysis of variance with Dunnett’s post testing. Diffuse signal changes were observed post-biopsy throughout the PZ. No significant signal change occurred following biopsy within the TZ. Left and right PZ mean nT2-SI (left PZ: 5.73, 5.16, 4.90 and 5.12; right PZ: 5.80, 5.10, 4.84 and 5.05 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) and mean T10 (left PZ: 1.02, 0.67, 0.78, 0.85; right PZ: 1.29, 0.64, 0.78, 0.87 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) were reduced significantly (P<0.05) from pre-biopsy values for up to 6 months post biopsy. Significant changes (P<0.05) of PZ-ME and AUC120 were observed at 1 month but resolved by 2 months post biopsy. PZ ADC did not change significantly following biopsy (P=0.23–1.0). There was no significant change of any TZ mp-MRI parameter at any time point following biopsy (P=0.1–1.0). Significant PZ (but not TZ) T2 signal changes persist up to 6 months post biopsy, whereas PZ and TZ ADC is not significantly altered as early as 1 month post biopsy. Caution must be exercised when interpreting T1- and T2-weighted imaging early post biopsy, whereas ADC images are more likely to maintain clinical efficacy.
TL;DR: Preliminary data are provided to suggest that RT 3 days per week compared with 2 daysper week may improve the strength and physical functioning in prostate cancer survivors, but may also blunt improvements in psychosocial functioning.
Abstract: Effects of resistance training frequency on physical functioning and quality of life in prostate cancer survivors: a pilot randomized controlled trial
TL;DR: Overall low CSM rates were revealed despite the highly unfavorable clinical disease, suggesting that less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment.
Abstract: The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option.
TL;DR: PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose, which may help provide modifiable targets in preventing recurrence of PCa.
Abstract: Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort
TL;DR: PSF1 is expressed in high-grade prostate cancer and may be a useful biomarker to identify patients with a poor prognosis at the time of diagnosis, and correlated significantly with PSA values at diagnosis.
Abstract: Partner of SLD5 1 (PSF1) is an evolutionarily conserved DNA replication factor. Previous studies have suggested that transcriptional activity of the PSF1 gene correlated with malignancy of cancer cells. The objective of the current study was to evaluate the relationship between PSF1 expression and the clinical features of prostate cancer. We determined the expression of PSF1 in 120 needle biopsy samples of prostate cancer by immunohistochemistry. We divided patients into PSF1-positive or -negative groups and analyzed the relationships between the expression of PSF1, the Gleason score, PSA level, TNM classification and prognosis. Our results showed that the PSF1 expression correlated significantly with PSA values at diagnosis (P=0.0028), with tumor grade (P<0.0001), and with clinical stage (P=0.0005). Moreover, the PSF1 expression correlated significantly with overall survival (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.17–15.8; P=0.003) and progression-free survival in 99 consecutive patients with prostate cancer. Noteworthy, the prognosis of PSF1-positive cases was also worse in patients with a Gleason score of 8–10 (HR 3.7; 95% CI 1.28–13.43; P=0.0143). Limitations include that this study had a retrospective design, that patients in the study were heterogeneous and included those with early and advanced cancer, and that small tumor fragments may not be representative of the entire carcinoma. PSF1 is expressed in high-grade prostate cancer and may be a useful biomarker to identify patients with a poor prognosis at the time of diagnosis.