Shilpa S. Mehta

The Changing Face of Low-Risk Prostate Cancer: Trends in Clinical Presentation and Primary Management

PURPOSE Early intervention for prostate cancer is associated with excellent long-term survival, but many affected men, especially those with low-risk disease characteristics, might not experience adverse impact to survival or quality of life were treatment deferred. We sought to characterize temporal trends in clinical presentation and primary disease management among patients with low-risk prostate cancer. METHODS Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 8,685 men with various stages of prostate cancer. Included were 2,078 men who were diagnosed between 1989 and 2001 and had a serum prostate specific antigen </= 10 ng/mL, Gleason sum </= 6, and clinical T stage </= 2a. Trends in risk distribution, tumor characteristics, and primary treatment were evaluated. RESULTS The proportion of patients with low-risk tumor characteristics rose from 29.8% in 1989 to 1992, to 45.3% in 1999 to 2001 (P <.0001). There have been sharp increases in the use of brachytherapy and androgen deprivation monotherapy, from 3.1% and 3.1%, to 12.0% and 21.7%, respectively. Utilization rates for prostatectomy, external-beam radiotherapy, and observation have fallen accordingly, from 63.8%, 16.1%, and 13.8%, to 51.6%, 6.8%, and 7.9% (P <.0001 for all except prostatectomy [P =.0019]). Age and socioeconomic status were significantly associated with treatment selection, but overall, the treatment trends were echoed on subgroup analysis of patients 75 years or older. CONCLUSION Low-risk features characterize a growing proportion of prostate cancer patients, and there have been significant shifts in the management of low-risk disease. Overtreatment may be a growing problem, especially among older patients.

Role of Surgeon Volume in Radical Prostatectomy Outcomes

PURPOSE To examine the effect of hospital and surgeon volume on postoperative outcomes and to determine whether hospital or surgeon volume is the stronger predictor. PATIENTS AND METHODS Using 1997 to 1998 claims data from a national 5% random sample of Medicare beneficiaries, we identified 2,292 men who underwent radical prostatectomy at 1,210 hospitals by 1,788 surgeons. Hospitals were classified as high (> or = 60 per year) or low (< 60 per year) volume according to radical prostatectomy experience over the 2-year period. Surgeons were classified as high (> or = 40 per year) or low (< 40 per year) volume. Multivariate logistic regression was performed to control for patient demographics and comorbidities when assessing the association of hospital and surgeon volume with in-hospital complications, length of stay, and anastomotic stricture rates. In-hospital complications included cardiac, respiratory, vascular, wound, genitourinary, and miscellaneous surgical and medical conditions. RESULTS High-volume surgeons had half the complication risk (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.32 to 0.89) and shorter lengths of stay (4.1 v 5.2 days, P =.03) compared with low-volume surgeons. High-volume hospital patients tended to have fewer anastomotic strictures (OR = 0.72; 95% CI, 0.49 to 1.04). Patient age (> or = 75 years) was associated with more complications (OR = 1.9; 95% CI, 1.39 to 2.70), more anastomotic strictures (OR = 2.2; 95% CI, 1.54 to 3.15), and longer hospital stays (parameter estimate = 2.26; 95% CI, 1.75 to 2.77). CONCLUSION Surgeon volume is inversely related to in-hospital complications and length of stay in men undergoing radical prostatectomy. Hospital volume is not significantly associated with outcomes after adjusting for physician volume. Further study is necessary to elucidate the mechanism of the volume-outcome effect.

Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer.

Although once reserved for the management of metastatic prostate cancer, androgen deprivation therapy (ADT) is being used increasingly to treat lower stages of disease. We sought to assess patterns of ADT use in a contemporary cohort of men newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer who had > or =12 months of follow-up evaluation were identified in a national disease registry of patients with prostate cancer. The patterns of ADT use, both primary and secondary, were characterized and stratified by risk according to prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort of 1485 men, 46% underwent ADT at some point during their treatment: 41% as primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk disease characteristics. Among patients treated with radical prostatectomy and radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients, respectively. Secondary hormonal manipulation was observed in 5% and 7% of patients treated initially with surgery or radiation, respectively. ADT is commonly used to treat men with prostate cancer. Much of the use of ADT is in men with low- and intermediate-risk disease characteristics. The appropriateness of such therapy requires further study, including its effect, not only on disease endpoints, but also on resource utilization and health-related quality of life.

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.

Predicting disease recurrence in intermediate and high-risk patients undergoing radical prostatectomy using percent positive biopsies: results from CaPSURE

OBJECTIVES To determine whether percent positive biopsies could be used to predict the probability of disease recurrence in contemporary patients undergoing radical prostatectomy in community-based practice settings. Previous studies have demonstrated the importance of systematic prostate biopsy results in the risk assessment for newly diagnosed patients with prostate cancer. METHODS We studied 1265 patients enrolled in CaPSURE (a longitudinal registry of patients with prostate cancer) who underwent radical prostatectomy as definitive local treatment of their prostate cancer. Preoperative characteristics, including age, race, prostate-specific antigen (PSA) level at diagnosis, clinical T stage, biopsy Gleason score, and percent positive prostate biopsies at the time of diagnosis, were determined for each patient. Disease recurrence was defined as PSA level of 0.2 ng/mL or greater on two consecutive occasions after radical prostatectomy or the occurrence of a second cancer treatment more than 6 months after surgery. Cox proportional regression analysis was performed to determine the significant independent predictors of disease recurrence. Patients were assigned to previously described risk groups on the basis of clinical tumor stage, PSA at diagnosis, and biopsy Gleason score. The likelihood of disease recurrence for each risk group, stratified according to the percentage of positive biopsies (0% to 33%, 34% to 66%, and more than 66%), was determined using the Kaplan-Meier method and compared using the log-rank test. RESULTS The median follow-up was 3.3 years after surgery. The serum PSA level at diagnosis, biopsy Gleason score, percent positive biopsies, and ethnicity were significant independent predictors of disease recurrence. The percentage of positive prostate biopsies was a significant predictor of disease recurrence for low, intermediate, and high-risk patients. For patients with high-risk disease, the likelihood of disease recurrence 5 years after surgery was 24%, 34%, and 59% for patients with 0% to 33%, 34% to 66%, and more than 66% positive biopsies, respectively. CONCLUSIONS Serum PSA, biopsy Gleason score, and percent positive biopsies were significant predictors of disease recurrence in this population. The percent positive biopsies may be useful in identifying high-risk patients suitable for definitive local therapy.

Predictors of Secondary Cancer Treatment in Patients Receiving Local Therapy for Prostate Cancer: Data From Cancer of the Prostate Strategic Urologic Research Endeavor

PURPOSE Secondary cancer treatment is common after definitive local therapy for prostate cancer and it may be an indicator of the efficacy and cost of primary local treatment. We determined predictors of secondary cancer treatment in patients initially treated with radical prostatectomy or external beam radiation. MATERIALS AND METHODS We examined 2,336 patients in Cancer of the Prostate Strategic Urologic Research Endeavor, a longitudinal registry of patients with prostate cancer, who underwent initial treatment with radical prostatectomy (1,744) or external beam radiation (592). Patients had at least 1 month of followup and all pretreatment information was available. The percent of patients receiving secondary cancer treatment, time to secondary treatment and type of secondary treatment delivered was determined. Multivariate analysis was done to determine independent predictors of secondary cancer treatment. In patients initially treated with prostatectomy a similar analysis was performed to identify predictors of receiving androgen deprivation versus radiation. RESULTS A total of 590 patients (25%) received secondary cancer treatment, including prostatectomy in 391 (22%) and radiation in 199 (34%). Secondary cancer treatment was equally divided between radiation and androgen deprivation in 52% and 47%, respectively, of those initially treated with prostatectomy, while 92% initially treated with radiation received androgen deprivation. Predictors of any secondary treatment included patient age, biopsy Gleason score and prostate specific antigen at diagnosis. There was a trend toward increased secondary treatment more than 6 months after local therapy in patients initially treated with radiation. Increased age and lymph node metastases were independent predictors of receiving androgen deprivation after prostatectomy, while there was increased use of radiation in patients with positive surgical margins or extracapsular disease extension. CONCLUSIONS Secondary treatment differs in patients initially treated with radical prostatectomy and radiation. Pretreatment factors can be used to counsel patients regarding the likelihood of secondary treatment, while age and prostatectomy results appear to determine the type of secondary treatment in those initially treated with prostatectomy.

Psychological Impact of Erectile Dysfunction: Validation of a New Health Related Quality of Life Measure for Patients With Erectile Dysfunction

PURPOSE Male erectile dysfunction has a substantial impact on health related quality of life. We examined the psychometric properties of 2 new scales created to measure the psychological impact of erectile dysfunction. MATERIALS AND METHODS Patients enrolled in a long-term study of men with erectile dysfunction completed clinical and health related quality of life information at baseline and at 3 followup points. The questionnaire incorporated a number of standard scales of psychosocial characteristics as well as questions developed from comments made during focus groups of men with erectile dysfunction and of their female partners. Principal components analysis was used to identify underlying constructs in response to the new questions. RESULTS A total of 168 men completed the baseline quality of life questionnaire. The principal components analysis of the psychological impact of erectile dysfunction questions resulted in 2 new scales. Reliability was good with an internal consistency reliability of 0.91 for scale 1 and 0.72 for scale 2. Test-retest reliability was 0.76 and 0.66, respectively. Men reporting a greater psychological impact of erectile dysfunction also reported greater impairment in functional status, lower sexual self-efficacy, greater depression and anxiety at the last intercourse. Each new scale significantly differentiated men with mild/moderate versus severe erectile dysfunction. CONCLUSIONS We developed 2 new scales to measure the psychological impact of erectile dysfunction and they showed good reliability and validity. These new scales, named the Psychological Impact of Erectile Dysfunction instrument, comprehensively capture the psychological effect of erectile dysfunction on health related quality of life, which is not adequately assessed by existing patient centered measures of erectile function.

Contemporary trends in imaging test utilization for prostate cancer staging: Data from the cancer of the prostate strategic urologic research endeavor

PURPOSE Previous investigators have reported widespread overuse of imaging tests for staging clinically localized prostate cancer. In this study imaging test utilization rates were analyzed in a contemporary group of patients, and clinical and demographic predictors of testing were identified. MATERIALS AND METHODS Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a longitudinal registry of men with various stages of prostate cancer. A total of 4,966 men met study inclusion criteria of available treatment and staging data. The rates of computerized tomography, magnetic resonance imaging and bone scans performed between the dates of diagnosis and primary treatment were analyzed in patients at 3 levels of clinical risk based on serum prostate specific antigen, Gleason sum and T stage. Time trends in test utilization were analyzed by linear regression. Contemporary rates were compared with those identified in a previous analysis of an earlier CaPSURE cohort. Demographic and clinical predictors of utilization were identified using generalized linear model analysis. RESULTS Since June 1997, the overall use of staging tests has decreased 63%, 25.9% and 11.4% in patients at low, intermediate and high risk, respectively. The most precipitous decrease was noted for bone scan but the use of cross-sectional imaging also decreased in all groups. Utilization rates were lower in 2001 than in any other year studied in CaPSURE. CONCLUSIONS The rates of testing decreased significantly in all risk groups. However, in the absence of established clinical practice guidelines many patients at low and intermediate risk continue to undergo unnecessary testing, while a growing number of those at high risk are proceeding to treatment without previous imaging.

How potent is potent? Evaluation of sexual function and bother in men who report potency after treatment for prostate cancer: data from CaPSURE.

OBJECTIVES To characterize the association between potency and comprehensive sexual function. The accurate assessment of sexual function is critical for the evaluation of outcomes after treatment of prostate cancer. The assessments of potency typically used in this context, however, may be oversimplified. METHODS CaPSURE is a large, observational database of men with prostate cancer. Participants complete health-related quality-of-life questionnaires, including the University of California, Los Angeles Prostate Cancer Index, every 6 months after treatment. A total of 5135 men completed at least one questionnaire and did not use medications for erectile function. The men were categorized as potent or impotent based on their ability to have erections and/or intercourse in the prior 4 weeks. Using the remaining questions on the Prostate Cancer Index, sexual function and bother scores were calculated for each group. RESULTS Of the 5135 men, 27.4% were potent. The mean sexual function scores were 56 and 13 for potent and impotent men, respectively (P <0.0001). The corresponding mean bother scores were 62 and 36 (P <0.0001). The function scores ranged from 0 to 100 and 0 to 92 among potent and impotent men, respectively, and bother scores from 0 to 100 in both groups. Function was inversely associated with age in both groups, but bother did not change among potent men and ameliorated among impotent men. Individual Prostate Cancer Index questions correlated with potency to a variable extent. CONCLUSIONS Although potent and impotent men have divergent sexual function and bother scores after treatment, the wide range of these scores in both groups denotes a complex picture of sexual function. The simple documentation of potency after treatment provides an insufficient measure of sexual health-related quality of life and should be supplemented with more comprehensive measures.

Is ethnicity an independent predictor of prostate cancer recurrence after radical prostatectomy

PURPOSE Prostate cancer incidence and mortality are higher in black than in white American men. We determined whether ethnicity is an independent predictor of disease recurrence in men undergoing radical prostatectomy. MATERIALS AND METHODS We studied 1,468 patients who underwent radical prostatectomy at the University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor database, a longitudinal disease registry of patients with prostate cancer. Preoperative characteristics, including age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage, biopsy Gleason score and percent positive prostate biopsies at diagnosis were determined in each patient. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment at least 6 months after surgery. Cox proportional hazards analysis was performed to determine independent predictors of time to disease recurrence. To control for pretreatment disease characteristics simultaneously patients were assigned to previously described risk groups based on clinical tumor stage, PSA at diagnosis and biopsy Gleason score. The likelihood of disease recurrence per risk group stratified according to ethnicity was determined using the Kaplan-Meier method and compared using the log rank test. Additional multivariate analysis was performed in the subset of patients enrolled in Cancer of the Prostate Strategic Urological Research Endeavor on whom education and income information was available. RESULTS Disease recurred in 304 of the 1,468 patients (21%). Black ethnicity, serum PSA at diagnosis, biopsy Gleason score and percent positive prostate biopsies were independent predictors of recurrence on multivariate analysis. Black ethnicity remained an independent predictor of disease recurrence in the multivariate model after stratifying patients into risk groups (p = 0.0007). Ethnicity was most important in patients at high risk, in whom estimated 5-year disease-free survival was 65% and 28% in white and black men, respectively. Education, income and ethnicity correlated highly. When education and income were entered into the multivariate model, ethnicity was no longer an independent predictor of outcome after prostatectomy. CONCLUSIONS Ethnicity appears to be an independent predictor of disease recurrence after adjusting for pretreatment measures of disease extent in patients undergoing radical prostatectomy. It appears to be particularly important in those with high risk disease characteristics. However, black ethnicity, education and income are highly correlated variables, suggesting that sociodemographic factors may contribute to the poorer outcomes in black patients even after adjusting for differences in pretreatment disease characteristics.