Race-dependent association of clinical trial participation with improved outcomes for high-risk prostate cancer patients treated in the modern era.

It is unclear whether cancer patients enrolled in clinical trials have improved outcomes compared with non-study patients. We compared prostate cancer-specific mortality (PCSM) in patients in a real-world setting (SEER-Medicare database) versus on a trial (NRG/RTOG 0521). The 7-year freedom from PCSM was superior in trial patients (92.4% vs. 88.1%, sHR = 1.77 [95% CI 1.05-2.97], P = 0.03). Black trial patients had significantly superior freedom from PCSM than Black real-world patients (sHR 6.52, 95% CI 1.43-29.72, P = 0.02), which was not seen among non-Black patients. Trial patients may have improved outcomes, and racial disparities are accentuated in the real world.

Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics.

BACKGROUND: Several definitions have attempted to stratify metastatic castrate-sensitive prostate cancer (mCSPC) into low and high-volume states. However, at this time, comparison of these definitions is limited. Here we aim to compare definitions of metastatic volume in mCSPC with respect to clinical outcomes and mutational profiles. METHODS: We performed a retrospective review of patients with biochemically recurrent or mCSPC whose tumors underwent somatic targeted sequencing. 294 patients were included with median follow-up of 58.3 months. Patients were classified into low and high-volume disease per CHAARTED, STAMPEDE, and two numeric (≤3 and ≤5) definitions. Endpoints including radiographic progression-free survival (rPFS), time to development of castration resistance (tdCRPC), and overall survival (OS) were evaluated with Kaplan-Meier survival curves and log-rank test. The incidence of driver mutations between definitions were compared. RESULTS: Median OS and tdCRPC were shorter for high-volume than low-volume disease for all four definitions. In the majority of patients (84.7%) metastatic volume classification did not change across all four definitions. High volume disease was significantly associated with worse OS for all four definitions (CHAARTED: HR 2.89; p < 0.01, STAMPEDE: HR 3.82; p < 0.01, numeric ≤3: HR 4.67; p < 0.01, numeric ≤5: HR 3.76; p < 0.01) however, were similar for high (p = 0.95) and low volume (p = 0.79) disease across all four definitions. Those with discordant classification tended to have more aggressive clinical behavior and mutational profiles. Patients with low-volume disease and TP53 mutation experienced a more aggressive course with rPFS more closely mirroring high-volume disease. CONCLUSIONS: The spectrum of mCSPC was confirmed across four different metastatic definitions for clinical endpoints and genetics. All definitions were generally similar in classification of patients, outcomes, and genetic makeup. Given these findings, the simplicity of numerical definitions might be preferred, especially when integrating metastasis directed therapy. Incorporation of tumor genetics may allow further refinement of current metastatic definitions.

Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Mapping expanded prostate cancer index composite to EQ5D utilities to inform economic evaluations in prostate cancer: Secondary analysis of NRG/RTOG 0415.

PURPOSE: The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities. METHODS AND MATERIALS: This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE). RESULTS: A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28-1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: "EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)- 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)"; RMSE was 0.10462. CONCLUSIONS: This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations.

Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.

Acute hematologic toxicity is a frequent adverse effect of beta-emitter targeted radionuclide therapies (TRTs). Alpha emitters have the potential of delivering high linear energy transfer (LET) radiation to the tumor attributed to its shorter range. Antibody-based TRTs have increased blood-pool half-lives, and therefore increased marrow toxicity, which is a particular concern with alpha emitters. Accurate 3D absorbed dose calculations focusing on the interface region of blood vessels and bone can elucidate energy deposition patterns. Firstly, a cylindrical geometry model with a central blood vessel embedded in the trabecular tissue was modeled. Monte Carlo simulations in GATE were performed considering beta (177Lu, 90Y) and alpha emitters (211At, 225Ac) as sources restricted to the blood pool. Subsequently, the radioactive sources were added in the trabecular bone compartment in order to model bone marrow metastases infiltration (BMMI). Radial profiles, dose-volume histograms and voxel relative differences were used to evaluate the absorbed dose results. We demonstrated that alpha emitters have a higher localized energy deposition compared to beta emitters. In the cylindrical geometry model, when the sources are confined to the blood pool, the dose to the trabecular bone is greater for beta emitting radionuclides, as alpha emitters deposit the majority of their energy within 70 µm of the vessel wall. In the BMMI model, alpha emitters have a lower dose to untargeted trabecular bone. Our results suggest that when alpha emitters are restricted to the blood pool, as when labeled to antibodies, hematologic toxicities may be lower than expected due to differences in the microdistribution of delivered absorbed dose.

Cost-Effectiveness of Metastasis-Directed Therapy in Oligorecurrent Hormone-Sensitive Prostate Cancer.

PURPOSE: Oligorecurrent prostate cancer has historically been treated with indefinite androgen deprivation therapy (ADT), although many patients and providers opt to defer this treatment at the time of recurrence given quality-of-life and/or comorbidity considerations. Recently, metastasis-directed therapy (MDT) has emerged as a potential intermediary between surveillance and immediate continuous ADT. Simultaneously, advanced systemic therapy in addition to ADT has also been shown to improve survival in metastatic hormone-sensitive disease. This study aimed to compare the cost-effectiveness of treating oligorecurrent patients with upfront MDT before standard-of-care systemic therapy. METHODS AND MATERIALS: A Markov-based cost-effectiveness analysis was constructed comparing 3 strategies: (1) upfront MDT → salvage abiraterone acetate plus prednisone (AAP) + ADT → salvage docetaxel + ADT; (2) upfront AAP + ADT → salvage docetaxel + ADT; and (3) upfront docetaxel + ADT → salvage AAP + ADT. Transition probabilities and utilities were derived from the literature. Using a 10-year time horizon and willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY), net monetary benefit values were subsequently calculated for each treatment strategy. RESULTS: At 10 years, the base case revealed a total cost of $141,148, $166,807, and $136,154 with QALYs of 4.63, 4.89, and 4.00, respectively, reflecting a net monetary benefit of $322,240, $322,018, and $263,407 for upfront MDT, upfront AAP + ADT, and upfront docetaxel + ADT, respectively. In the probabilistic sensitivity analysis using a Monte Carlo simulation (1,000,000 simulations), upfront MDT was the cost-effective strategy in 53.6% of simulations. The probabilistic sensitivity analysis revealed 95% confidence intervals for cost ($75,914-$179,862, $124,431-$223,892, and $103,298-$180,617) and utility in QALYs (3.85-6.12, 3.91-5.86, and 3.02-5.22) for upfront MDT, upfront AAP + ADT, and upfront docetaxel + ADT, respectively. CONCLUSIONS: At 10 years, upfront MDT followed by salvage AAP + ADT, is comparably cost-effective compared with upfront standard-of-care systemic therapy and may be considered a viable treatment strategy, especially in patients wishing to defer systemic therapy for quality-of-life or comorbidity concerns. Additional studies are needed to determine whether MDT causes a sustained meaningful delay in disease natural history and whether any benefit exists in combining MDT with upfront advanced systemic therapy.

Prostate cancer incidence across stage, NCCN risk groups, and age before and after USPSTF Grade D recommendations against prostate-specific antigen screening in 2012.

BACKGROUND: We sought to determine the extent to which US Preventive Services Task Force (USPSTF) 2012 Grade D recommendations against prostate-specific antigen screening may have impacted recent prostate cancer disease incidence patterns in the United States across stage, National Comprehensive Cancer Network (NCCN) risk groups, and age groups. METHODS: SEER*Stat version 8.3.4 was used to calculate annual prostate cancer incidence rates from 2010 to 2015 for men aged ≥50 years according to American Joint Committee on Cancer stage at diagnosis (localized vs metastatic), NCCN risk group (low vs unfavorable [intermediate or high-risk]), and age group (50-74 years vs ≥75 years). Age-adjusted incidences per 100,000 persons with corresponding year-by-year incidence ratios (IRs) were calculated using the 2000 US Census population. RESULTS: From 2010 to 2015, the incidence (per 100,000 persons) of localized prostate cancer decreased from 195.4 to 131.9 (Ptrend  < .001) and from 189.0 to 123.4 (Ptrend  < .001) among men aged 50-74 and ≥75 years, respectively. The largest relative year-by-year decline occurred between 2011 and 2012 in NCCN low-risk disease (IR, 0.77 [0.75-0.79, P < .0001] and IR 0.68 [0.62-0.74, P < .0001] for men aged 50-74 and ≥75 years, respectively). From 2010-2015, the incidence of metastatic disease increased from 6.2 to 7.1 (Ptrend  < .001) and from 16.8 to 22.6 (Ptrend  < .001) among men aged 50-74 and ≥75 years, respectively. CONCLUSIONS: This report illustrates recent prostate cancer "reverse migration" away from indolent disease and toward more aggressive disease beginning in 2012. The incidence of localized disease declined across age groups from 2012 to 2015, with the greatest relative declines occurring in low-risk disease. Additionally, the incidence of distant metastatic disease increased gradually throughout the study period.

A Circulating Tumor Cell-RNA Assay for Assessment of Androgen Receptor Signaling Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.

Rationale: Our objective was to develop a circulating tumor cell (CTC)-RNA assay for characterizing clinically relevant RNA signatures for the assessment of androgen receptor signaling inhibitor (ARSI) sensitivity in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We developed the NanoVelcro CTC-RNA assay by combining the Thermoresponsive (TR)-NanoVelcro CTC purification system with the NanoString nCounter platform for cellular purification and RNA analysis. Based on the well-validated, tissue-based Prostate Cancer Classification System (PCS), we focus on the most aggressive and ARSI-resistant PCS subtype, i.e., PCS1, for CTC analysis. We applied a rigorous bioinformatic process to develop the CTC-PCS1 panel that consists of prostate cancer (PCa) CTC-specific RNA signature with minimal expression in background white blood cells (WBCs). We validated the NanoVelcro CTC-RNA assay and the CTC-PCS1 panel with well-characterized PCa cell lines to demonstrate the sensitivity and dynamic range of the assay, as well as the specificity of the PCS1 Z score (the likelihood estimate of the PCS1 subtype) for identifying PCS1 subtype and ARSI resistance. We then selected 31 blood samples from 23 PCa patients receiving ARSIs to test in our assay. The PCS1 Z scores of each sample were computed and compared with ARSI treatment sensitivity. Results: The validation studies using PCa cell line samples showed that the NanoVelcro CTC-RNA assay can detect the RNA transcripts in the CTC-PCS1 panel with high sensitivity and linearity in the dynamic range of 5-100 cells. We also showed that the genes in CTC-PCS1 panel are highly expressed in PCa cell lines and lowly expressed in background WBCs. Using the artificial CTC samples simulating the blood sample conditions, we further demonstrated that the CTC-PCS1 panel is highly specific in identifying PCS1-like samples, and the high PCS1 Z score is associated with ARSI resistance samples. In patient bloods, ARSI-resistant samples (ARSI-R, n=14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n=17) (Rank-sum test, P=0.003). In the analysis of 8 patients who were initially sensitive to ARSI (ARSI-S) and later developed resistance (ARSI-R), we found that the PCS1 Z score increased from the time of ARSI-S to the time of ARSI-R (Pairwise T-test, P=0.016). Conclusions: Using our new methodology, we developed a first-in-class CTC-RNA assay and demonstrated the feasibility of transforming clinically-relevant tissue-based RNA profiling such as PCS into CTC tests. This approach allows for detecting RNA expression relevant to clinical drug resistance in a non-invasive fashion, which can facilitate patient-specific treatment selection and early detection of drug resistance, a goal in precision oncology.

Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial.

IMPORTANCE: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. OBJECTIVE: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. MAIN OUTCOMES AND MEASURES: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. RESULTS: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. CONCLUSIONS AND RELEVANCE: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

Self-reported Conflicts of Interest and Trial Sponsorship of Clinical Trials in Prostate Cancer Involving Radiotherapy.

OBJECTIVES: To examine the association between trial sponsorship and conflicts of interest (COI) with clinical trial conclusions for prostate cancer trials related to radiotherapy. MATERIALS AND METHODS: The MEDLINE database was searched for all prostate cancer clinical trials published between 2004 and 2013 and identified 1396 studies. Two investigators independently identified trials published in the English language of ≥30 patients, and extracted relevant data. Clinical trials were classified according to trial characteristics, sponsorship source and type, COI, and study conclusion, and analyzed by univariable and multivariable logistic regression. RESULTS: Of 240 eligible trials, 160 (67.5%) evaluated drugs without radiotherapy, 60 (25%) involved radiotherapy, and 18 (7.5%) involved procedures without radiotherapy. Of the 60 radiotherapy trials eligible for analysis, positive sponsorship and potential COI were present in 58.3% and 20% of trials, respectively. Study conclusions were positive, negative, or neutral in 78.3%, 5%, and 16.7% of trials, respectively. No association was found between positive conclusions and either industry support of potential COI. Positive conclusions were reported in 86.7% and 83.3% of trials with sponsorship and COI, respectively, as compared with 75.6% and 77.1% of those without sponsorship (P=0.37) and COI (P=0.64). Sponsorship was significantly associated with radiotherapy trials combined with drugs (odds ratio 5.5, P=0.01) and higher-risk disease (odds ratio 4.71, P=0.01). CONCLUSIONS: The presence of sponsorship was associated with radiotherapy trials involving drugs or studying higher-risk prostate cancer. However, there were no identified associations between study conclusion and sponsorship type or COI.

Multinational Prospective Study of Patient-Reported Outcomes After Prostate Radiation Therapy: Detailed Assessment of Rectal Bleeding.

PURPOSE: The new short Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) patient-reported health-related quality of life (HRQOL) tool has removed the rectal bleeding question from the previous much longer version, EPIC-26. Herein, we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospective multicenter cohorts. METHODS AND MATERIALS: In a prospective multicenter test cohort (n=865), EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011. A second prospective multicenter cohort (n=442) was used for independent validation. A repeated-effects model was used to predict the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores. RESULTS: Two years after radiation therapy, 91% of patients were free of bleeding, and only 2.6% reported bothersome bleeding problems. Correlations between EPIC-26 and EPIC-CP bowel scores were very high (r2=0.90-0.96) and were statistically improved with the addition of rectal bleeding information (r2=0.94-0.98). Considering all patients, only 0.2% of patients in the test cohort and 0.7% in the validation cohort reported bothersome bleeding and had clinically relevant HRQOL changes missed with EPIC-CP. However, of the 2.6% (n=17) of men with bothersome rectal bleeding in the test cohort, EPIC-CP failed to capture 1 patient (6%) as experiencing meaningful declines in bowel HRQOL. CONCLUSIONS: Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding, and <1% of patients experience bothersome bleeding and are not captured by EPIC-CP as having meaningful HRQOL declines after radiation therapy. However, in the small subset of patients with bothersome rectal bleeding, the longer EPIC-26 should strongly be considered, given its superior performance in this patient subset.

Limitations of the Cancer of the Prostate Risk Assessment (CAPRA) Prognostic Tool for Prediction of Metastases and Prostate Cancer-specific Mortality in Patients Treated With External Beam Radiation Therapy.

OBJECTIVES: To assess the performance of the Cancer of the Prostate Risk Assessment (CAPRA) prognostic tool for freedom-from-metastases (FFM) and cause-specific survival (CSS) in patients with localized prostate cancer treated with definitive external beam radiotherapy (EBRT), and to determine whether the performance of CAPRA is influenced by androgen deprivation therapy (ADT) use or the presence of Gleason pattern 5 (GP-5). MATERIALS AND METHODS: A total of 612 patients from a prospective database of 718 patients treated with dose-escalated EBRT from 1998 to 2008 who met CAPRA scoring criteria were included in the study. Performance of CAPRA and association of CAPRA score, GP-5 and short-term or long-term ADT use (STAD or LTAD, respectively) with FFM and CSS were evaluated using Cox models. The impact of ADT use on accuracy of the CAPRA-based CaPSURE model for CSS was assessed. The discriminatory ability of the CAPRA model and modified models incorporating GP-5 and ADT use were compared using the C-index. RESULTS: Increasing CAPRA score correlated with worse FFM and CSS, and was prognostic for FFM and CSS for the overall cohort. CAPRA showed poorer discrimination for FFM and CSS in patients treated with EBRT+LTAD than those who received EBRT alone or EBRT+STAD. The addition of GP-5 and ADT use to CAPRA score increased the predictive accuracy of the CAPRA model for both FFM (C-index 0.809 vs. 0.779, P<0.001) and CSS (C-index 0.864 vs. 0.796, P=0.003). CONCLUSIONS: The CAPRA score should be modified to incorporate GP-5 and ADT use for risk adjustment and risk prediction in prostate cancer patients who receive EBRT.

Investigation of the diffusion abnormality index as a new imaging biomarker for early assessment of brain tumor response to radiation therapy.

BACKGROUND: Diffusion MRI, although having the potential to be a biomarker for early assessment of tumor response to therapy, could be confounded by edema and necrosis in or near the brain tumors. This study aimed to develop and investigate the ability of the diffusion abnormality index (DAI) to be a new imaging biomarker for early assessment of brain metastasis response to radiation therapy (RT). METHODS: Patients with either radiosensitive or radioresistant brain metastases that were treated by whole brain RT alone or combined with bortezomib as a radiation sensitizer had diffusion-weighted (DW) MRI pre-RT and 2 weeks (2W) after starting RT. A patient-specific diffusion abnormality probability function (DAProF) was created to account for abnormal low and high apparent diffusion coefficients differently, reflecting respective high cellularity and edema/necrosis. The DAI of a lesion was then calculated by the integral of DAProF-weighted tumor apparent diffusion coefficient histogram. The changes in DAI from pre-RT to 2W were evaluated for differentiating the responsive, stable, and progressive tumors and compared with the changes in gross tumor volume and conventional diffusion metrics during the same time interval. RESULTS: In lesions treated with whole brain RT, the DAI performed the best among all metrics in predicting the posttreatment response of brain metastases to RT. In lesions treated with whole brain RT + bortezomib, although DAI was the best predictor, the performance of all metrics worsened compared with the first group. CONCLUSIONS: The ability of DAI for early assessment of brain metastasis response to RT depends upon treatment regimes.

12th Annual meeting of the Society of Urologic Oncology (SUO) bladder cancer sessions I and II summary report.

Health care reform with the Affordable Care Act aims to control health care costs, in part, through the use of comparative effectiveness research and quality of care measures. Bladder cancer is one of the most expensive malignancies to manage as related to the need for continuous monitoring and the treatment of recurrence. The use of clinical practice guidelines relying on evidence based medicine in the management of patients with bladder cancer will help to ensure quality of care and cost containment. The goal of session I was to provide a thorough discussion of the quality of care and cost issues related to bladder cancer including an examination of levels of evidence, implementation and compliance with clinical practice guidelines, the use of standardized reporting methodologies, and comparative effectiveness research. Bladder cancer is a common malignancy with a variable biology and natural history. Although the majority of patients are diagnosed with non-invasive disease, approximately 20-40% of patients either present with or develop more advanced disease. The 5-year survival for patients with lymph node involvement at the time of surgery is 20-30% and patients with metastatic disease treated with chemotherapy have a median survival of only 15 months. Novel approaches for the management of patients with bladder cancer are desperately needed. The goal of session II was to review the current state of translational research in bladder cancer as related to both early and late stage disease including a discussion of novel molecular targets and targeted therapeutics, pharmacogenomics to predict response to therapy, and exploring the role for agents targeting angiogenesis.

The Cancer of the Prostate Risk Assessment (CAPRA) in patients treated with external beam radiation therapy: evaluation and optimization in patients at higher risk of relapse.

BACKGROUND: The Cancer of the Prostate Risk Assessment (CAPRA) was developed to predict freedom from biochemical failure (FFBF) following radical prostatectomy (RP). Its utility following external beam radiation therapy (EBRT) has not been externally evaluated. METHODS: A retrospective study of 612 patients treated with dose-escalated EBRT at the University of Michigan Medical Center. RESULTS: Compared to the derivation cohort, EBRT treated patients had higher-risk disease (28% with CAPRA of 6-10 vs. 5%, respectively). A total of 114 patients (19%) had BF with 5-year BF ranging from 7% with CAPRA 0-3 to 35% with CAPRA 7-10. For RT patients the risk of BF at 5-year was similar to 4 surgical cohorts for CAPRA scores 0-2 but lower for all CAPRA scores ≥ 3. The difference favoring RT increased with increasing CAPRA score reaching a 27-50% absolute improved at 5-years for CAPRA scores of 6-10. On multivariate analysis each CAPRA point increased the risk of BF (p<0.0001) while Gleason pattern 5 in the biopsy also increased BF (p=0.01) and long-term androgen deprivation therapy (ADT) significantly reduced the risk of BF (p=0.015). CONCLUSIONS: Compared to surgical series the risk of BF was lower with dose-escalated EBRT with the greatest difference at the highest CAPRA scores.