Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States.

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales. SIGNIFICANCE: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals.

Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma.

BACKGROUND: Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. METHODS: In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. RESULTS: A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. CONCLUSION: The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. CLINICAL TRIAL REGISTRATION: NCT02935309.

Number of Unfavorable Intermediate-Risk Factors Predicts Pathologic Upstaging and Prostate Cancer-Specific Mortality Following Radical Prostatectomy: Results From the SEARCH Database.

BACKGROUND: To validate and further improve the stratification of intermediate risk prostate cancer into favorable and unfavorable subgroups for patients undergoing radical prostatectomy. MATERIALS AND METHODS: The SEARCH database was queried for IR patients undergoing radical prostatectomy without adjuvant radiotherapy. UIR disease was defined any patient with at least one unfavorable risk factor (URF), including primary Gleason pattern 4, 50% of more biopsy cores containing cancer, or multiple National Comprehensive Cancer Network IR factors. RESULTS: One thousand five hundred eighty-six patients with IR prostate cancer comprised the study cohort. Median follow-up was 62 months. Patients classified as UIR were significantly more likely to have pathologic high-risk features, such as Gleason score 8 - 10, pT3-4 disease, or lymph node metastases, than FIR patients (P < 0.001). Furthermore, UIR patients had significantly higher rates of PSA-relapse (PSA, hazard ratio [HR] = 1.89, P < 0.001) and distant metastasis (DM, HR = 2.92, P = 0.001), but no difference in prostate cancer-specific mortality (PCSM) or all-cause mortality in multivariable analysis. On secondary analysis, patients with ≥2 URF had significantly worse PSA-RFS, DM, and PCSM than those with 0 or 1 URF. Moreover, 40% of patients with ≥2 URF had high-risk pathologic features. CONCLUSIONS: Patients with UIR prostate cancer are at increased risk of PSA relapse, DM, and pathologic upstaging following prostatectomy. However, increased risk of PCSM was only detected in those with ≥2 URF. This suggests that further refinement of the UIR subgroup may improve risk stratification. Prostate Prostate 77:154-163, 2017. © 2016 Wiley Periodicals, Inc.

Is clinical stage T2c prostate cancer an intermediate- or high-risk disease?

BACKGROUND: Clinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. According to the D'Amico grouping and American Urological Association guidelines, cT2c is a high risk, whereas the National Comprehensive Cancer Network and the European Urological Association classify cT2c as an intermediate risk. This study assessed whether cT2c tumors without other high-risk factors (clinical stage T2c, not otherwise specified [cT2c-NOS]) behaved as an intermediate or high risk through an analysis of biochemical recurrence (BCR) after radical prostatectomy. METHODS: Two thousand seven hundred fifty-nine men from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database and 12,900 men from Johns Hopkins Hospital (JHH) from 1988-2011 and 1982-2012, respectively, were analyzed. Patients were grouped into low-risk (prostate-specific antigen [PSA] < 10 ng/mL, Gleason sum ≤ 6, and cT1-T2a), intermediate-risk (PSA = 10-20 ng/mL, Gleason sum = 7, or cT2b), and high-risk PC categories (PSA > 20 ng/mL, Gleason sum = 8-10, or cT3). Men with cT2c tumors who were not otherwise at high risk (ie, PSA< 20 ng/mL and Gleason sum < 8) were placed into a separate category termed cT2c-NOS. Associations between cT2c-NOS and intermediate- and high-risk patients and BCR were tested with the log-rank test and Cox proportional analysis models. RESULTS: Ninety-nine men (4%) from SEARCH and 202 men (2%) from JHH had tumors classified as cT2c-NOS. The cT2c-NOS patients had a BCR risk similar to that of the intermediate-risk patients (SEARCH, P = .27; JHH, P = .23) but a significantly lower BCR risk in comparison with the high-risk patients (SEARCH, P < .001; JHH, P < .001). When they were specifically compared with intermediate- and high-risk patients, after adjustments for year and center, cT2c-NOS patients had outcomes comparable to those of intermediate-risk patients (SEARCH, P = .53; JHH, P = .54) but significantly better than those of high-risk patients (SEARCH, P = .003; JHH, P < .001). CONCLUSIONS: Patients with cT2c disease without other high-risk features had outcomes similar to the outcomes of patients with intermediate-risk PC and significantly better than the outcomes of patients with high-risk PC. These findings suggest that men with cT2c disease should be considered to be at intermediate risk.

Ambrosia pollen in Tulsa, Oklahoma: aerobiology, trends, and forecasting model development.

BACKGROUND: Ambrosia pollen is an important aeroallergen in North America; the ability to predict daily pollen levels may provide an important benefit for sensitive individuals. OBJECTIVE: To analyze the long-term Ambrosia pollen counts and develop a forecasting model to predict the next day's pollen concentration. METHODS: Airborne pollen has been collected since December 1986 with a Burkard spore trap at the University of Tulsa. Summary statistics and season metrics were calculated for the 27 years of data. Concentration and previous-day meteorologic data from 1987 to 2011 were used to develop a multiple regression model to predict pollen levels for the following day. Model output was compared to 2012 and 2013 ragweed pollen data. RESULTS: The Tulsa ragweed season extends from the middle of August to late October. The mean start date is August 22, the mean peak date is September 10, and the mean end date is October 20. The mean cumulative season total is 11,599 pollen/m(3), and the mean daily concentration is 197 pollen/m(3). Previous-day meteorologic and phenologic data were positively related to pollen concentration (P < .001). Precipitation was modeled as a dichotomous variable. The final model included minimum temperature, dichotomous precipitation, dew point, and phenology variable (R = 0.7146, P < .001). Analysis of the model's accuracy revealed that the model was highly representative of the 2012 and 2013 seasons (R = 0.680, P < .001). CONCLUSION: Multiple regression models may be useful in explaining the variability of Ambrosia pollen levels. Further testing of the modeling parameters in different geographical areas is needed.