Genetic Testing in Men With Metastatic Castration-Resistant Prostate Cancer.

This cross-sectional study assesses homologous recombination repair mutation genetic testing and associated characteristics among men with metastatic castration-resistant prostate cancer (mCRPC).

The prognostic value of Eastern Cooperative Oncology Group performance status on overall survival among patients with metastatic prostate cancer: a systematic review and meta-analysis.

Background: There is heterogeneity in the literature regarding the strength of association between Eastern Cooperative Oncology Group performance status (ECOG PS) and mortality. We conducted a systematic review and meta-analysis of studies reporting the prognostic value of ECOG PS on overall survival (OS) in metastatic prostate cancer (mPC). Methods: PubMed was searched from inception to March 21, 2022. A meta-analysis pooling the effect of ECOG PS categories (≥2 vs. <2, 2 vs. <2, and ≥1 vs. <1) on OS was performed separately for studies including patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) using a random-effects model. Analyses were stratified by prior chemotherapy and study type. Results: Overall, 75 studies, comprising 32,298 patients, were included. Most studies (72/75) included patients with mCRPC. Higher ECOG PS was associated with a significant increase in mortality risk, with the highest estimate observed among patients with mCRPC with an ECOG PS of ≥2 versus <2 (hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.87-2.37). When stratifying by study type, there was a higher risk estimate of mortality among patients with mCRPC with an ECOG PS of ≥1 versus <1 in real-world data studies (HR: 1.98, 95% CI: 1.72-2.26) compared with clinical trials (HR: 1.32, 95% CI: 1.13-1.54; p < 0.001). There were no significant differences in the HR of OS stratified by previous chemotherapy. Conclusion: ECOG PS was a significant predictor of OS regardless of category, previous chemotherapy, and mPC population. Additional studies are needed to better characterize the effect of ECOG PS on OS in mCSPC.

The use of aspirin and the risk of mortality in patients with prostate cancer.

PURPOSE: The association between the use of aspirin and mortality in patients with prostate cancer remains uncertain. We determine whether the use of aspirin in patients with prostate cancer is associated with a decreased risk of prostate cancer mortality and all cause mortality. MATERIALS AND METHODS: Using the United Kingdom National Cancer Data Repository, Clinical Practice Research Datalink and associated databases, we identified a cohort of men with nonmetastatic prostate cancer between 1998 and 2009, followed until 2012. Cox proportional hazards models were used to estimate adjusted HRs with 95% CIs of mortality outcomes associated with post-diagnostic use of aspirin defined as a time-varying exposure. Effect modification by pre-diagnostic aspirin use was also assessed. RESULTS: The cohort included 11,779 men followed for 5.4 years (SD 2.9). Post-diagnostic aspirin use was associated with an increased risk of prostate cancer mortality (HR 1.46, 95% CI 1.29-1.65) and all cause mortality (HR 1.37, 95% CI 1.26-1.50). These increased risks were restricted to patients initiating aspirin after the prostate cancer diagnosis (HR 1.84, 95% CI 1.59-2.12, and HR 1.70, 95% CI 1.53-1.88, respectively), and not in patients who were already exposed to aspirin before the diagnosis (HR 0.97, 95% CI 0.81-1.16 and HR 0.98, 95% CI 0.87-1.18, respectively). CONCLUSIONS: The post-diagnostic use of aspirin is not associated with a decreased risk of prostate cancer outcomes. Increased risks were restricted to patients initiating these drugs after their diagnosis, suggesting a noncausal association.

Post-diagnostic use of beta-blockers and the risk of death in patients with prostate cancer.

BACKGROUND: Recent observational studies have produced conflicting results with respect to beta-blocker use after prostate cancer diagnosis and mortality outcomes. OBJECTIVE: To determine whether post-diagnostic use of beta-blockers is associated with prostate cancer mortality and all-cause mortality. PATIENTS AND METHODS: A cohort of 6270 men newly-diagnosed with non-metastatic prostate cancer between 1st April 1998, and 31st December 2009, followed until 1st October 2012, was identified using large population-based electronic databases from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality outcomes associated with post-diagnostic use of beta-blockers. Secondary analyses were performed to examine the independent effects of non-selective beta-blockers, as well as cumulative duration of use. RESULTS: During a mean follow-up time of 3.8 years (standard deviation: 2.7 years), 1761 deaths occurred, including 715 from prostate cancer. Post-diagnostic use of beta-blockers was not associated with a decreased risk of prostate cancer mortality (HR: 0.97, 95% CI: 0.72-1.31) and all-cause mortality (HR: 0.97, 95% CI: 0.81-1.16). There was no statistically significant association for non-selective beta-blockers (prostate cancer mortality, HR: 1.05, 95% CI: 0.72-1.53 and all-cause mortality, HR: 0.94, 95% CI: 0.74-1.18), and no statistically significant trends of cumulative duration of use for both mortality outcomes. CONCLUSION: The use of beta blockers, including those of the non-selective type, was not associated with a decreased risk of prostate cancer and all-cause mortality.

Androgen deprivation therapy and the risk of colorectal cancer in patients with prostate cancer.

PURPOSE: Androgens are known to play an important protective role on colorectal carcinogenesis, and thus the objective of this study was to determine whether androgen deprivation therapy (ADT) is associated with an increased risk of incident colorectal cancer in patients with prostate cancer. METHODS: We conducted a population-based cohort study within the UK General Practice Research Database population which included all patients newly diagnosed with prostate cancer between 1 January 1988 and 31 December 2008, followed until 31 December 2009. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of incident primary colorectal cancer associated with the use of ADT. Secondary analyses considered cumulative duration of use and specific ADTs. RESULTS: The cohort included a total of 21,503 patients, of whom 184 were diagnosed with colorectal cancer during a mean (SD) follow-up 4.0 (3.0) years (rate 2.4/1,000 person-years). Overall, use of ADT was not associated with an increased risk of colorectal cancer (HR 0.99, 95 % CI 0.73-1.35). Similarly, no association was observed in terms of duration use, although this secondary analysis may have been limited by statistical power. With respect to specific ADTs, bilateral orchiectomy was the only therapy associated with an increased risk of colorectal cancer (HR 2.50, 95 % CI 1.13-5.52). CONCLUSION: Overall, the use of ADT is not associated with an increased risk of incident colorectal cancer. The increased risk observed with bilateral orchiectomy may possibly be due to the prolonged androgen suppression of this therapy.

The impact of the type of insurance plan on adherence and persistence with antidepressants: a matched cohort study.

OBJECTIVE: To compare adherence to, and persistence with, antidepressants (AD) in Quebec patients who are covered by private and public drug insurance. METHOD: A matched cohort study was conducted using prescription claims databases: reMed, a medication data registry for Quebec residents covered by private drug insurance, and Régie de l'assurance maladie du Québec database for Quebec residents with public drug insurance. Patients were aged 18 to 64 years and filled at least 1 prescription for an AD in monotherapy between December 2007 and September 2009 (194 privately and 2055 publicly insured patients). Adherence over 1 year was estimated using the proportion of prescribed days covered (PPDC). The difference in mean PPDC between patients with private and public drug insurance was estimated with linear regression. Persistence was compared between the groups with a Cox regression model. RESULTS: The PPDC was 86.4% (95% CI 83.3% to 89.5%) in privately insured and 82.2% (95% CI 78.5% to 85.9%) in publicly insured patients and the adjusted mean difference was 5.1% (95% CI 1.6% to 8.6%). Persistence was 51.0% in the private group and 19.7% in the public group at 1 year (P < 0.001); the adjusted hazard ratio was 0.49 (95% CI 0.30 to 0.79). CONCLUSION: Better adherence and persistence were observed in privately insured patients. Adherence difference may be due to lower copayment among privately insured patients.

Incidence, risk factors, and obstetrical outcomes of women with breast cancer in pregnancy.

Breast cancer in pregnancy is a rare condition. The objective of our study was to describe the incidence, risk factors, and obstetrical outcomes of breast cancer in pregnancy. We conducted a population-based cohort study on 8.8 million births using data from the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample from 1999-2008. The incidence of breast cancer was calculated and logistic regression analysis was used to evaluate the independent effects of demographic determinants on the diagnosis of breast cancer and to estimate the adjusted effect of breast cancer on obstetrical outcomes. There were 8,826,137 births in our cohort of which 573 cases of breast cancer were identified for an overall 10-year incidence of 6.5 cases per 100,000 births with the incidence slightly increasing over the 10-year period. Breast cancer appeared to be more common among women >35 years of age, odds ratio (OR)=3.36 (2.84-3.97); women with private insurance plans, OR=1.39 (1.10-1.76); and women who delivered in an urban teaching hospital, OR=2.10 (1.44-3.06). After adjusting for baseline characteristics, women with pregnancy-associated breast cancer were more likely to have an induction of labor, OR=2.25 (1.88, 2.70), but similar rates of gestational diabetes, preeclampsia, instrumental deliveries, and placental abruption. The incidence of breast cancer in pregnancy appears higher than previously reported with women over 35 being at greatest risk. Aside from an increased risk for induction of labor, women with breast cancer in pregnancy have similar obstetrical outcomes.

The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study.

OBJECTIVE: To determine if the use of pioglitazone is associated with an increased risk of incident bladder cancer in people with type 2 diabetes. DESIGN: Retrospective cohort study using a nested case-control analysis. SETTING: Over 600 general practices in the United Kingdom contributing to the general practice research database. PARTICIPANTS: The cohort consisted of people with type 2 diabetes who were newly treated with oral hypoglycaemic agents between 1 January 1988 and 31 December 2009. All incident cases of bladder cancer occurring during follow-up were identified and matched to up to 20 controls on year of birth, year of cohort entry, sex, and duration of follow-up. Exposure was defined as ever use of pioglitazone, along with measures of duration and cumulative dosage. MAIN OUTCOME MEASURE: Risk of incident bladder cancer associated with use of pioglitazone. RESULTS: The cohort included 115,727 new users of oral hypoglycaemic agents, with 470 patients diagnosed as having bladder cancer during follow-up (rate 89.4 per 100,000 person years). The 376 cases of bladder cancer that were diagnosed beyond one year of follow-up were matched to 6699 controls. Overall, ever use of pioglitazone was associated with an increased rate of bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate increased as a function of duration of use, with the highest rate observed in patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a cumulative dosage greater than 28,000 mg (2.54, 1.05 to 6.14). CONCLUSION: The use of pioglitazone is associated with an increased risk of incident bladder cancer among people with type 2 diabetes.

Correlating metabolic activity on 18F-FDG PET/CT with histopathologic characteristics of osseous and soft-tissue sarcomas: a retrospective review of 136 patients.

OBJECTIVE: The objective of our study was to determine whether there is a statistically significant correlation between metabolic activity of osseous and soft-tissue sarcomas as measured by the maximum standardized uptake value (SUV(max)) on (18)F-FDG PET/CT and histopathologic characteristics such as mitotic counts, the presence of necrosis, and the presence of a myxoid component. MATERIALS AND METHODS: We retrospectively evaluated 238 consecutive patients with known soft-tissue or osseous sarcoma who underwent (18)F-FDG PET/CT for initial staging or assessment for recurrence of disease. The SUV(max) of each primary or of the most intense metastatic lesion was measured and was compared with the histologic data provided in the final pathology reports. RESULTS: Histopathologic data were available for 136 sarcomas. The median SUV(max) values of sarcomas with mitotic counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00-6.99, 7.00-16.24, and 16.25 or greater were 5.0, 6.6, 10.3, and 13.0, respectively (p = 0.0003). The median SUV(max) for the sarcomas with necrosis (90 patients) was 8.6 and for those without necrosis (43 patients), 6.0 (p = 0.026). The median SUV(max) for the sarcomas without a myxoid component (118 patients) was 7.7 and with a myxoid component (16 patients) was 6.2 (p = 0.28). CONCLUSION: There was a statistically significant correlation between the mitotic count and the SUV(max) as well as between the presence of tumor necrosis and the SUV(max). Although a correlation between the presence of a myxoid component and SUV(max) was shown, it was not found to be statistically significant. These findings improve on the current information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy. Correlating the SUV(max) with histologic markers that also feature prominently in major sarcoma grading systems may help improve the accuracy of grading and of prognostication by allowing the SUV(max) to potentially serve as a surrogate marker in these grading systems, particularly in cases in which there is interobserver disagreement in the pathologic diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of histopathologic evaluation alone.