Assessment of prostate cancer progression using a translational needle photoacoustic sensing probe: Preliminary study with intact human prostates ex-vivo.

In our previous studies, we demonstrated the ability of an interstitial all-optical needle photoacoustic (PA) sensing probe and PA spectral analysis (PASA) to assess the aggressiveness of prostate cancer. In this clinical translation investigation, we integrated the optical components of the needle PA sensing probe into a 18G steel needle. The translational needle PA sensing probe was evaluated using intact human prostates in a simulated ultrasound-guided transperineal prostate biopsy. PA signals were acquired at 1220 nm, 1370 nm, 800 nm and 266 nm at each interstitial measurement location and quantified by PASA within the frequency range of 8-28 MHz. The measurement locations were stained for establishing spatial correlations between the quantitative measurements and the histological diagnosing. Most of the quantitative PA assessments reveal statistically significant differences between the benign and cancerous regions. Multivariate analysis combining the PASA quantifications shows an accuracy close to 90% in differentiating the benign and cancerous regions in the prostates.

Interstitial assessment of aggressive prostate cancer by physio-chemical photoacoustics: An ex vivo study with intact human prostates.

PURPOSE: Transrectal ultrasound (TRUS)-guided biopsy is the standard procedure for evaluating the presence and aggressiveness of prostate cancer. TRUS biopsy involves tissue removal, and suffers from low core yield as well as high false negative rate. A less invasive and more accurate diagnostic procedure for prostate cancer is therefore highly desired. Combining the optical sensitivity and ultrasonic resolution to resolve the spatial distribution of the major molecular components in tissue, photoacoustic (PA) technology could be an alternative approach for the diagnosis of prostate cancer. The purpose of this study was to examine the feasibility of identifying aggressive prostate cancer using interstitial PA measurements. METHODS: Seventeen patients with prebiopsy magnetic resonance imaging (MRI), TRUS biopsies, and planned prostatectomies were enrolled in this study. The interstitial PA measurements were achieved using our recently developed needle PA probe, which was inserted into the ex vivo prostates in the fashion of a biopsy needle. A total of 70 interstitial PA measurements were acquired. The PA measurements were quantified by a previously established PA physio-chemical analysis (PAPCA) method. The histology has confirmed the nonaggressive and aggressive cancerous conditions at the insertion locations. The diagnostic accuracy was also compared to that provided by the prebiopsy MRI. RESULTS: The quantitative study shows significant differences between the individual parameters of the nonaggressive and the aggressive cancerous regions (P < 0.005). Multivariate analysis of the quantitative features achieved a diagnostic accuracy of 78.6% for differentiating nonaggressive and aggressive prostate cancer tissues. CONCLUSIONS: The proposed procedure has shown promises in the diagnosis of aggressive prostate cancer.

Cost-effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer.

OBJECTIVE: To determine how best to use magnetic resonance imaging (MRI) and targeted MRI/ultrasonography fusion biopsy for early detection of prostate cancer (PCa) in men with elevated prostate-specific antigen (PSA) concentrations and whether it can be cost-effective. METHODS: A Markov model of PCa onset and progression was developed to estimate the health and economic consequences of PCa screening with MRI. Patients underwent PSA screening from ages 55 to 69 years. Patients with elevated PSA concentrations (>4 ng/mL) underwent MRI, followed by targeted fusion or combined (standard + targeted fusion) biopsy on positive MRI, and standard or no biopsy on negative MRI. Prostate Imaging Reporting and Data System (PI-RADS) score on MRI was used to determine biopsy decisions. Deaths averted, quality-adjusted life-years (QALYs), cost and incremental cost-effectiveness ratio (ICER) were estimated for each strategy. RESULTS: With a negative MRI, standard biopsy was more expensive and had lower QALYs than performing no biopsy. The optimum screening strategy (ICER $23 483/QALY) recommended combined biopsy for patients with PI-RADS score ≥3 and no biopsy for patients with PI-RADS score <3, and reduced the number of screening biopsies by 15%. Threshold analysis suggests MRI continues to be cost-effective when the sensitivity and specificity of MRI and combined biopsy are simultaneously reduced by 19 percentage points. CONCLUSIONS: Our analysis suggests MRI followed by targeted MRI/ultrasonography fusion biopsy can be a cost-effective approach to the early detection of PCa.

Optimizing active surveillance strategies to balance the competing goals of early detection of grade progression and minimizing harm from biopsies.

BACKGROUND: Active surveillance (AS) for prostate cancer includes follow-up with serial prostate biopsies. The optimal biopsy frequency during follow-up has not been determined. The goal of this investigation was to use longitudinal AS biopsy data to assess whether the frequency of biopsy could be reduced without substantially prolonging the time to the detection of disease with a Gleason score ≥ 7. METHODS: With data from 1375 men with low-risk prostate cancer enrolled in AS at Johns Hopkins, a hidden Markov model was developed to estimate the probability of undersampling at diagnosis, the annual probability of grade progression, and the 10-year cumulative probability of reclassification or progression to Gleason score ≥ 7. It simulated 1024 potential AS biopsy strategies for the 10 years after diagnosis. For each of these strategies, the model predicted the mean delay in the detection of disease with a Gleason score ≥ 7. RESULTS: The model estimated the 10-year cumulative probability of reclassification from a Gleason score of 6 to a Gleason score ≥ 7 to be 40.0%. The probability of undersampling at diagnosis was 9.8%, and the annual progression probability for men with a Gleason score of 6 was 4.0%. On the basis of these estimates, a simulation of an annual biopsy strategy estimated the mean time to the detection of disease with a Gleason score ≥ 7 to be 14.1 months; however, several strategies eliminated biopsies with only small delays (<12 months) in detecting grade progression. CONCLUSIONS: Although annual biopsy for low-risk men on AS is associated with the shortest time to the detection of disease with a Gleason score ≥ 7, several alternative strategies may allow less frequent biopsying without sizable delays in detecting grade progression. Cancer 2018;124:698-705. © 2017 American Cancer Society.

Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and Detection of Aggressive Prostate Cancer.

IMPORTANCE: Potential survival benefits from treating aggressive (Gleason score, ≥7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease. OBJECTIVE: To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort. INTERVENTIONS/EXPOSURES: Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy. MAIN OUTCOMES AND MEASURES: Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes. RESULTS: Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men. CONCLUSIONS AND RELEVANCE: Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.

Two-Stage Biomarker Protocols for Improving the Precision of Early Detection of Prostate Cancer.

BACKGROUND: New cancer biomarkers are being discovered at a rapid pace; however, these tests vary in their predictive performance characteristics, and it is unclear how best to use them. METHODS: We investigated 2-stage biomarker-based screening strategies in the context of prostate cancer using a partially observable Markov model to simulate patients' progression through prostate cancer states to mortality from prostate cancer or other causes. Patients were screened every 2 years from ages 55 to 69. If the patient's serum prostate-specific antigen (PSA) was over a specified threshold in the first stage, a second stage biomarker test was administered. We evaluated design characteristics for these 2-stage strategies using 7 newly discovered biomarkers as examples. Monte Carlo simulation was used to estimate the number of screening biopsies, prostate cancer deaths, and quality-adjusted life-years (QALYs) per 1000 men. RESULTS: The all-cancer biomarkers significantly underperformed the high-grade cancer biomarkers in terms of QALYs. The screening strategy that used a PSA threshold of 2 ng/mL and a second biomarker test with high-grade sensitivity and specificity of 0.86 and 0.62, respectively, maximized QALYs. This strategy resulted in a prostate cancer death rate within 1% of using PSA alone with a threshold of 2 ng/mL, while reducing the number of biopsies by 20%. Sensitivity analysis suggests that the results are robust with respect to variation in model parameters. CONCLUSIONS: Two-stage biomarker screening strategies using new biomarkers with risk thresholds optimized for high-grade cancer detection may increase quality-adjusted survival and reduce unnecessary biopsies.

Relief of Urinary Symptom Burden after Primary Prostate Cancer Treatment.

PURPOSE: Harms of prostate cancer treatment on urinary health related quality of life have been thoroughly studied. In this study we evaluated not only the harms but also the potential benefits of prostate cancer treatment in relieving the pretreatment urinary symptom burden. MATERIALS AND METHODS: In American (1,021) and Spanish (539) multicenter prospective cohorts of men with localized prostate cancer we evaluated the effects of radical prostatectomy, external radiotherapy or brachytherapy in relieving pretreatment urinary symptoms and in inducing urinary symptoms de novo, measured by changes in urinary medication use and patient reported urinary bother. RESULTS: Urinary symptom burden improved in 23% and worsened in 28% of subjects after prostate cancer treatment in the American cohort. Urinary medication use rates before treatment and 2 years after treatment were 15% and 6% with radical prostatectomy, 22% and 26% with external radiotherapy, and 19% and 46% with brachytherapy, respectively. Pretreatment urinary medication use (OR 1.4, 95% CI 1.0-2.0, p = 0.04) and pretreatment moderate lower urinary tract symptoms (OR 2.8, 95% CI 2.2-3.6) predicted prostate cancer treatment associated relief of baseline urinary symptom burden. Subjects with pretreatment lower urinary tract symptoms who underwent radical prostatectomy experienced the greatest relief of pretreatment symptoms (OR 4.3, 95% CI 3.0-6.1), despite the development of deleterious de novo urinary incontinence in some men. The magnitude of pretreatment urinary symptom burden and beneficial effect of cancer treatment on those symptoms were verified in the Spanish cohort. CONCLUSIONS: Men with pretreatment lower urinary tract symptoms may experience benefit rather than harm in overall urinary outcome from primary prostate cancer treatment. Practitioners should consider the full spectrum of urinary symptom burden evident before prostate cancer treatment in treatment decisions.

Treatment Availability Influences Physicians' Portrayal of Robotic Surgery During Clinical Appointments.

In order to empower patients as decision makers, physicians must educate them about their treatment options in a factual, nonbiased manner. We propose that site-specific availability of treatment options may be a novel source of bias, whereby physicians describe treatments more positively when they are available. We performed a content analysis of physicians' descriptions of robotic prostatectomy within 252 appointments at four Veterans Affairs medical centers where robotic surgery was either available or unavailable. We coded how physicians portrayed robotic versus open prostatectomy across specific clinical categories and in the appointment overall. We found that physicians were more likely to describe robotic prostatectomy as superior when it was available [F(1, 42) = 8.65, p = .005]. We also provide initial qualitative evidence that physicians may be shaping their descriptions of robotic prostatectomy in an effort to manage patients' emotions and demand for the robotic technology. To our knowledge, this is the first study to provide empirical evidence that treatment availability influences how physicians describe the advantages and disadvantages of treatment alternatives to patients during clinical encounters, which has important practical implications for patient empowerment and patient satisfaction.

Understanding Inpatient Cost Variation in Kidney Transplantation: Implications for Payment Reforms.

OBJECTIVE: To examine the magnitude and sources of inpatient cost variation for kidney transplantation. METHODS: We used the 2005-2009 Nationwide Inpatient Sample to identify patients who underwent kidney transplantation. We first calculated the patient-level cost of each transplantation admission and then aggregated costs to the hospital level. We fit hierarchical linear regression models to identify sources of cost variation and to estimate how much unexplained variation remained after adjusting for case-mix variables commonly found in administrative datasets. RESULTS: We identified 8866 living donor (LDRT) and 5589 deceased donor (DDRT) renal transplantations. We found that higher costs were associated with the presence of complications (LDRT, 14%; P <.001; DDRT, 24%; P <.001), plasmapheresis (LDRT, 27%; P <.001; DDRT, 27%; P <.001), dialysis (LDRT, 4%; P <.001), and prolonged length of stay (LDRT, 84%; P <.001; DDRT, 82%; P <.001). Even after case-mix adjustment, a considerable amount of unexplained cost variation remained between transplant centers (DDRT, 52%; LDRT, 66%). CONCLUSION: Although significant inpatient cost variation is present across transplant centers, much of the cost variation for kidney transplantation is not explained by commonly used risk-adjustment variables in administrative datasets. These findings suggest that although there is an opportunity to achieve savings through payment reforms for kidney transplantation, policymakers should seek alternative sources of information (eg, clinical registry data) to delineate sources of warranted and unwarranted cost variation.

Evaluation of point-of-care PRO assessment in clinic settings: integration, parallel-forms reliability, and patient acceptability of electronic QOL measures during clinic visits.

PURPOSE: Assessment of patient-reported outcomes (PROs), such as health-related quality of life, has become an important component of healthcare that measures the impact of disease and medical treatment on patient health. Collecting PROs during point-of-care assessments and integrating them into the clinical setting, however, remains challenging. The objective of this pilot study was to evaluate the reliability, usability, and acceptability of point-of-care electronic PRO assessments implemented in a prostate cancer clinic. METHODS: Fifty subjects completed paper-pencil and computerized formats of the Expanded Prostate Cancer Index Composite (EPIC), a validated, condition-specific QOL instrument, at separate times before treatment. Parallel-forms reliability was evaluated by comparing mean scores, variations in response distribution, and correlations between administration formats. Correlation coefficients of at least 0.70 were used for reliability testing. Differences between administration forms, indicating potential bias, were compared using the signed-rank test. A 6-item acceptability scale was also used to evaluate patient acceptability and satisfaction with the electronic format. RESULTS: Mean scores and standard deviations were similar between the paper-pencil and electronic forms across all EPIC instrument domains, and no assessment bias was found. Each EPIC domain demonstrated a high reliability between administration formats (correlation coefficients: 0.70-0.98). The majority (>90 %) of respondents found that the computerized QOL format was user friendly and simple to use. CONCLUSIONS: Point-of-care computerized QOL assessments were reliable and acceptable to patients in this study, supporting the feasibility of PRO integration at the point-of-care in clinical settings.

A Generalized Assessment of the Impact of Regionalization and Provider Learning on Patient Outcomes.

We present a generalized model to assess the impact of regionalization on patient care outcomes in the presence of heterogeneity in provider learning. The model characterizes best regionalization policies as optimal allocations of patients across providers with heterogeneous learning abilities. We explore issues that arise when solving for best regionalization, which depends on statistically estimated provider learning curves. We explain how to maintain the problem's tractability and reformulate it into a binary integer program problem to improve solvability. Using our model, best regionalization solutions can be computed within reasonable time using current-day computers. We apply the model to minimally invasive radical prostatectomy and estimate that, in comparison to current care delivery, within-state regionalization can shorten length of stay by at least 40.8%.

Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment.

BACKGROUND: TMPRSS2:ERG (T2:ERG) and prostate cancer antigen 3 (PCA3) are the most advanced urine-based prostate cancer (PCa) early detection biomarkers. OBJECTIVE: Validate logistic regression models, termed Mi-Prostate Score (MiPS), that incorporate serum prostate-specific antigen (PSA; or the multivariate Prostate Cancer Prevention Trial risk calculator version 1.0 [PCPTrc]) and urine T2:ERG and PCA3 scores for predicting PCa and high-grade PCa on biopsy. DESIGN, SETTING, AND PARTICIPANTS: T2:ERG and PCA3 scores were generated using clinical-grade transcription-mediated amplification assays. Pretrained MiPS models were applied to a validation cohort of whole urine samples prospectively collected after digital rectal examination from 1244 men presenting for biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Area under the curve (AUC) was used to compare the performance of serum PSA (or the PCPTrc) alone and MiPS models. Decision curve analysis (DCA) was used to assess clinical benefit. RESULTS AND LIMITATIONS: Among informative validation cohort samples (n=1225 [98%], 80% from patients presenting for initial biopsy), models incorporating T2:ERG had significantly greater AUC than PSA (or PCPTrc) for predicting PCa (PSA: 0.693 vs 0.585; PCPTrc: 0.718 vs 0.639; both p<0.001) or high-grade (Gleason score >6) PCa on biopsy (PSA: 0.729 vs 0.651, p<0.001; PCPTrc: 0.754 vs 0.707, p=0.006). MiPS models incorporating T2:ERG score had significantly greater AUC (all p<0.001) than models incorporating only PCA3 plus PSA (or PCPTrc or high-grade cancer PCPTrc [PCPThg]). DCA demonstrated net benefit of the MiPS_PCPTrc (or MiPS_PCPThg) model compared with the PCPTrc (or PCPThg) across relevant threshold probabilities. CONCLUSIONS: Incorporating urine T2:ERG and PCA3 scores improves the performance of serum PSA (or PCPTrc) for predicting PCa and high-grade PCa on biopsy. PATIENT SUMMARY: Incorporation of two prostate cancer (PCa)-specific biomarkers (TMPRSS2:ERG and PCA3) measured in the urine improved on serum prostate-specific antigen (or a multivariate risk calculator) for predicting the presence of PCa and high-grade PCa on biopsy. A combined test, Mi-Prostate Score, uses models validated in this study and is clinically available to provide individualized risk estimates.

Sexual Health Concerns Among Cancer Survivors: Testing a Novel Information-Need Measure Among Breast and Prostate Cancer Patients.

While it is recognized that cancer treatment can contribute to problems in sexual function, much less is currently known about the specific sexual health concerns and information needs of cancer survivors. This study tested a new instrument to measure cancer survivors' sexual health concerns and needs for sexual information after cancer treatment. The Information on Sexual Health: Your Needs after Cancer (InSYNC), developed by a multidisciplinary team of experts, is a novel 12-item questionnaire to measure sexual health concerns and information needs of cancer survivors. We tested the measure with a sample of breast and prostate cancer survivors. A convenience sample of 114 cancer survivors (58 breast, 56 prostate) was enrolled. Results of the InSYNC questionnaire showed high levels of sexual concern among cancer survivors. Areas of concern differed by cancer type. Prostate cancer survivors were most concerned about being able to satisfy their partners (57 %) while breast cancer survivors were most concerned with changes in how their bodies worked sexually (46 %). Approximately 35 % of all cancer survivors wanted more information about sexual health. Sexual health concerns and unmet information needs are common among breast and prostate cancer survivors, varying in some aspects by type of cancer. Routine screening for sexual health concerns should be included in comprehensive cancer survivorship care to appropriately address health care needs. The InSYNC questionnaire is one tool that may help clinicians identify concerns facing their patients.

Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.

BACKGROUND: In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. METHODS: The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. RESULTS: Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters. CONCLUSIONS: The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival.

Multicenter Evaluation of the Prostate Health Index to Detect Aggressive Prostate Cancer in Biopsy Naïve Men.

PURPOSE: We evaluated the ability of PHI to discriminate aggressive prostate cancer from indolent or no cancer in a biopsy naïve population. MATERIALS AND METHODS: Two independent prospective cohorts of 561 and 395 subjects, respectively, with no prior prostate biopsy who were enrolled at different clinical sites were used to validate the results. We compared the diagnostic specificity of PHI to prebiopsy total and percent free prostate specific antigen using prostate biopsy results. We also determined the optimal PHI threshold to discriminate aggressive prostate cancer (Gleason score 7 or greater) from indolent or no prostate cancer (Gleason score 6 or less). RESULTS: In the primary cohort higher PHI values were significantly associated with Gleason score 7 or greater. The AUC to detect aggressive prostate cancer was 0.815. At 95% sensitivity PHI specificity was 36.0% vs 17.2% and 19.4% for total and percent free prostate specific antigen, respectively. At 95% sensitivity for detecting aggressive prostate cancer the optimal PHI cutoff was 24, which would help avoid 41% of unnecessary biopsies. A cutoff of 24 led to 36% biopsies avoided with few aggressive cancers missed. These results were confirmed in the validation cohort. CONCLUSIONS: The PHI detected aggressive prostate cancer with better specificity than total and percent free prostate specific antigen in a biopsy naïve population. It could be a useful tool to decrease unnecessary prostate biopsies.

Variation in use of active surveillance among men undergoing expectant treatment for early stage prostate cancer.

PURPOSE: We examined variation in active surveillance use in Medicare eligible men undergoing expectant treatment for early stage prostate cancer. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology and End Results) and Medicare data we identified 49,192 men diagnosed with localized prostate cancer from 2004 through 2007. Of 7,347 patients who did not receive treatment (ie expectant management) within 12 months of diagnosis we assessed the prevalence of active surveillance (ie repeat prostate biopsy and prostate specific antigen measurement) vs watchful waiting across health care markets. We fit multivariable logistic regression models to examine associations of active surveillance with patient demographics, cancer severity and health care market characteristics. RESULTS: During the study interval use of active surveillance vs watchful waiting increased significantly in patients treated expectantly from 9.7% in 2004 to 15.3% in 2007 (p <0.001). Active surveillance was less common in older patients, those with high risk tumors and those with more comorbidities (each p <0.001). Patients who were white and had higher socioeconomic status were more likely to receive active surveillance (each p <0.05). After adjusting for patient and tumor characteristics significant differences in the predicted probability of active surveillance persisted across health care markets (range 2.4% to 30.1%). No significant variation in active surveillance use was associated with specific health care market characteristics, including intensity of end of life care, Medicare reimbursement or provider density. CONCLUSIONS: Active surveillance has been relatively uncommon in Medicare beneficiaries with localized prostate cancer. Its use relative to watchful waiting varies based on patient demographics, tumor severity and geographic location.

Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study.

CONTEXT: Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment. The persistence of such symptoms over time necessitates an improvement of survivor care so that the medical and support needs of these patients are met. OBJECTIVE: This study aims to perform a patient-centered survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates, evaluate survivors' access to preventive care services post-prostate cancer treatment, and assess the informational needs of these survivors regarding their prostate cancer. DESIGN, SETTING, AND PATIENTS: Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on 31 December 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned. MAIN OUTCOME MEASURES: (1) Physical symptoms--assessing bowel, sexual, urinary, and vitality symptoms by treatment modality. (2) Access to care--identifying whether diagnostic tests for prostate cancer (prostate-specific antigen (PSA) and digital rectal examination) were performed. Determining whether the survivors had knowledge of the "watchful waiting" paradigm for prostate cancer surveillance. (3) Informational needs--assessing whether the informational needs of patients were addressed by providers. Evaluating the significant predictors associated with seeking information about prostate cancer from any other source. Identifying what factors influenced a person to actively seek out information and what factors guide which primary information source a survivor would use. RESULTS: Median duration between prostate cancer diagnosis and survey response was 9 years. Of the study population, 80 % was diagnosed at an early stage. Survivors had reported significant problems in the 4 weeks prior to survey. Of the survivors, 88.1 % reported having a PSA test since diagnosis of prostate cancer, with 93 % of them having it done at least once per year. Of the survivors, 82.6 % reported that a healthcare provider gave them information on prostate cancer. Of this 82.6 %, 86.4 % had this information provided by a urologist, 45.4 % by a primary care physician, and 29.2 % by an oncologist. The primary source of information for these survivors was "healthcare provider" (59.2 %). CONCLUSION: Persistent symptoms subsequent to prostate cancer treatment suggest a gap in symptom management. Future research should support long-term studies of active surveillance versus active treatment outcomes to understand the feasibility of minimizing the burden of long-term physical symptoms arising from prostate cancer treatment. Clinicians must assess post-treatment distress long after treatment has ended to identify when supportive care is needed. More informational resources should be allocated to prostate cancer survivors to ensure that they are well-educated about their prognosis. IMPLICATIONS FOR CANCER SURVIVORS: This study is needed to ensure that the post-treatment symptoms of prostate cancer survivors are properly addressed and managed by healthcare providers over the long term.

Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

IMPORTANCE: The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. OBJECTIVE: To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. DESIGN, SETTING, AND PATIENTS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. MAIN OUTCOMES AND MEASURES: The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. RESULTS: In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P < .001) and from 36% (95% CI, 35%-38%) to 57% (95% CI, 55%-59%) among men with high risk of noncancer mortality (P < .001). The use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P < .001). Among all patients diagnosed in SEER, the use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95% CI, 24%-25%), or 244.2 per 1000 patients diagnosed with prostate cancer (P < .001). CONCLUSION AND RELEVANCE: Among men diagnosed with prostate cancer between 2004 and 2009 who had low-risk disease, high risk of noncancer mortality, or both, the use of advanced treatment technologies has increased.

Differential adoption of laser prostatectomy for treatment of benign prostatic hyperplasia.

OBJECTIVE: To evaluate whether socioeconomic environment affects the adoption of new laser technology for treatment of benign prostatic hyperplasia (BPH). METHODS: Using all payer data, we identified all discharges for laser prostatectomy or transurethral resection of the prostate (TURP) performed in Florida (2001-2009). We determined whether or not each of 114 healthcare markets (Hospital Service Areas) offered laser prostatectomy or TURP and assessed the market-level socioeconomic environment using a previously described ZIP code-based summary score. We used generalized estimating equations to examine the association of socioeconomic environment with offering laser prostatectomy or TURP, adjusting for additional market characteristics. RESULTS: Better socioeconomic environment was associated with offering laser prostatectomy (odds ratio 1.21 for each 1 point increase in summary score, 95% confidence interval 1.08-1.35, P <.001). Adoption of laser prostatectomy over time was more rapid in markets with superior socioeconomic environment (P <.001 for interaction of socioeconomic summary score with year), such that by study midpoint, 82% of advantaged vs 54% of disadvantaged markets had adopted this new technology. In contrast, socioeconomic environment had only minimal effects on whether or not a market offered TURP. CONCLUSION: We found delayed access to new laser technology in more disadvantaged socioeconomic environments, which may translate into disparities in certain outcomes after transurethral surgery for BPH.

Managed care and the diffusion of intensity-modulated radiotherapy for prostate cancer.

OBJECTIVE: To better understand associations between managed care penetration in health care markets and the adoption of intensity-modulated radiotherapy (IMRT). METHODS: We used Surveillance, Epidemiology, and End Results-Medicare data to identify men diagnosed with prostate cancer between 2001 and 2007 who were treated with radiotherapy (n = 55,162). We categorized managed care penetration in Health Service Areas (HSAs) as low (<3%), intermediate (3%-10%), and high (>10%), and assessed our main outcomes (ie, probability of IMRT adoption, which is the ability of a health care market to deliver IMRT, and IMRT utilization in HSA markets) using a Cox proportional hazards model and Poisson regression model, respectively. RESULTS: Compared with markets with low managed care penetration, populations in highly penetrated HSAs were more racially diverse (25% vs 15% non-white, P <.01), densely populated (2110 vs 145 people/square mile, P <.01), and wealthier (median income, $48,500 vs $31,900, P <.01). The probability of IMRT adoption was greatest in markets with the highest managed care penetration (eg, 0.82 [high] vs 0.72 [low] in 2007, P = .05). Among adopting markets, the use of IMRT increased in all HSA categories. However, relative to markets with low managed care penetration, IMRT use was constrained in markets with the highest penetration (0.69 [high] vs 0.76 [low] in 2007, P <.01). CONCLUSION: Markets with higher managed care penetration demonstrated a greater propensity for acquiring IMRT technology. However, after adopting IMRT, more highly penetrated markets had roughly 7% slower growth in IMRT use during the study period. These findings provide insight into the implications of delivery system reforms for cancer-related technologies.