Overtreatment Of Prostate Cancer Research Articles

Cost Comparison Between Watchful Waiting With Active Surveillance and Active Treatment of Clinically Localized Prostate Cancer

In part because of concern regarding overtreatment in men with prostate cancer, watchful waiting with active surveillance (WWAS) has been increasingly used in men diagnosed with low-risk prostate cancer. The present study investigates the difference in costs between men with low-risk prostate cancer treated with up-front radical prostatectomy (RP) versus WWAS. A cost model was constructed using data from centers that have published their results in men who were followed up with WWAS compared with the actual costs of up-front RP calculated from a high volume center. Two WWAS arms of 15-year duration were created in which the follow-up protocol and conversion rate to active treatment were varied. The cost of up-front RP including costs of surgery, complications, and follow up for 15 years was $15 235 per person. Costs of WWAS were estimated using annual conversion rates from WWAS to RP of both 5% and 7%. Costs per person in the WWAS arms ranged from $6558 to $11 992 in the scenarios created which represent a 43%-78.7% reduction in costs when compared with men undergoing up-front RP. Watchful waiting with active surveillance is being increasingly used in hopes of decreasing the potential overtreatment of prostate cancer in men with low-risk disease. The present study suggests that WWAS is likely to markedly decrease costs when compared with active treatment with RP.

335 COST COMPARISON BETWEEN WATCHFUL WAITING WITH ACTIVE SURVEILLANCE AND ACTIVE TREATMENT FOR CLINICALLY LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Cost Effectiveness I1 Apr 2010335 COST COMPARISON BETWEEN WATCHFUL WAITING WITH ACTIVE SURVEILLANCE AND ACTIVE TREATMENT FOR CLINICALLY LOCALIZED PROSTATE CANCER Anthony Corcoran, Pamela Peele, and Ronald Benoit Anthony CorcoranAnthony Corcoran More articles by this author , Pamela PeelePamela Peele More articles by this author , and Ronald BenoitRonald Benoit More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.401AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In part due to the concern of overtreatment in men with prostate cancer, watchful waiting with active surveillance (WWAS) has been increasingly utilized in men diagnosed with low risk prostate cancer. The present study investigates the difference in costs between men with low risk prostate cancer treated with up front radical prostatectomy (RP) and men who undergo WWAS. METHODS A model was constructed using data from centers which have published their outcomes in men who were followed with WWAS. Two WWAS arms were created. Each arm varied both the follow up protocol and conversion rate to RP. The two WWAS arms were further stratified by the length of time men were assumed to undergo serial prostate biopsies with the potential to convert to active treatment, as well as the frequency of prostate biopsy. Annual conversion rates from WWAS to RP used in the models were 5% and 7% based on recent published outcomes of men undergoing WWAS. The costs of WWAS in these scenarios were compared to the cost of up front RP. The costs of complications resulting from radical prostatectomy were included in the costs of RP. Costs were calculated for 15 years from the time of diagnosis in all arms of the model. A discount rate of 5% was utilized to determine the present value of future costs. A sensitivity analysis was performed to test the robustness of the model by varying the assumptions used in the model. RESULTS Costs of up front RP including costs of surgery, complications, and follow up for 15 years were $15,235 per person. Costs per person in the WWAS arms ranged from $6,558 to $11,992 in the scenarios created, which represent a 21% - 57% reduction in costs when compared to treatment of these men with up front RP. CONCLUSIONS Watchful waiting with active surveillance is being increasingly practiced as a method to decrease potential overtreatment of prostate cancer in men with low risk disease. The present study demonstrates that WWAS is likely to markedly decrease costs when compared to active treatment with RP. Pittsburgh, PA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e133 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Corcoran More articles by this author Pamela Peele More articles by this author Ronald Benoit More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The impact of core biopsy fragmentation in prostate cancer

Since accurate tumor localization and quantification are essential requisites avoiding prostate cancer overtreatment, we analyzed the impact of core fragmentation and the relation between core biopsy taken and pathological information in regard to cancer extension and aggressiveness (Gleason score). One hundred and ninety-nine men submitted to trans-rectal prostate biopsy by the same urologist between October 2006 and October 2008 were included, and the number of cores obtained by biopsy compared to the number of cores examined by the same pathologist. Total core number obtained by biopsy was 21.54 (± 3.56) compared to 24.08 (± 4.77) examined by the pathologist, P < 0.01. Dividing prostate gland by areas such as base, mid and apical right and left, all areas showed statistically different core number between biopsy and pathological examination report (P < 0.01). Mean ratio of positive core cancer length was 0.41 (± 0.12) and 0.32 (± 0.8) comparing individual and overall cores analysis, respectively (P < 0.01). The mean Gleason score in the individual and overall cores analysis were 6.6 (6-9) and 6.3 (6-9), respectively, P < 0.01. Considering the ongoing trend for earlier diagnosis of increasing numbers of younger men with low-risk prostate cancer, this study is original and demonstrates the possibility of core fragmentation, explaining in part over- and under-staging. One core per container and an overall Gleason score and percentage of adenocarcinoma for each container are encouraged.

Active Surveillance for Localized Prostate Cancer – Current Practices and Recommendations

Prostate cancer is now the most commonly diagnosed solid tumor in American men, due in part to widespread screening and aggressive diagnostic practices. Prostate cancer autopsy studies show the uniquely high prevalence rates of small, indolent tumors in men dying of other causes. These findings have led to increased concern for the overdetection and overtreatment of prostate cancer. Active surveillance for prostate cancer allows one to limit prostate cancer treatment with concomitant risks of treatment-related morbidity to the men who will benefit the most from aggressive therapies. Several tools have been developed in treated and surveyed men to assist physicians in selecting men with potentially indolent tumors amenable to active surveillance. Recent published results describe institutional experiences with active surveillance and delayed selective therapy for men with low-grade, early prostate cancer. Although median follow-up from these studies is relatively short, the outcomes appear favorable. Data from these reports provide information for selecting men for this approach, as well as for following them over time and determining triggers for further intervention. Ongoing clinical trials with watchful waiting and active surveillance for prostate cancer will ultimately provide improved evidence for managing early, localized disease.

Use of an inhibitor of differentiation-1 (Id1) expression (exp) to discriminate good prognosis (GP) from poor prognosis (PP) prostate cancer (PCa)

e16128 Background: In the PSA era a significant proportion of PCa patients (pts) at onset have potential indolent tumors that will not impact their life expectancy or quality of life. Most of them will be radically treated and suffer its consequences. Thus, PCa overtreatment is a great concern among clinicians. Pre-treatment molecular factors may help differentiate indolent from aggressive PCa. Id1, involved in cell differentiation and angiogenesis, has recently showed to mediate lung metastasis (mts) from breast cancer. Its role in PCa endothelial (end) cells is well established but its exp and role in PCa cells is controversial. Using a new monoclonal antibody (MoAb) (195–14) for immunohistochemistry (IHC), Id1 exp is limited to some PP breast and bladder tumors. Whether Id1 exp is relevant in PCa prognosis is unknown. We tested 195–14 in PP and GP PCa samples and matched mts where available. Methods: 52 PCa pts were studied, 20 GP + 32 PP. All formalin-fixed and paraffin-embedded primary biopsies and matched mts of 16 of them were stained for tumor and end cell Id1 exp. 195–14 (1:500), (Biocheck), was used for IHC. Results: GP group: median age 65, all pts T2N0M0, median Gleason score 6 (6–9), median PSA at onset 5,5 ng/ml. After a median follow-up of 38 months (ms) 1 pt showed radiological and PSA progression (P); other PSA P. All but one remain alive. PP group: median age was 70, T3-T4 (70%), Gleason 8–10 (61%), median PSA at onset 58 ng/ml, 2 or more mts locations (79%), 94% showed P to docetaxel, median time-to- progression and overall survival after chemotherapy were 18 weeks and 7 ms. Among PP, 39% of primary PCa and 38% of mts showed Id1 tumor cell exp and 79% of primary tumors and 81% of mts showed end Id1 exp. In the GP group 0% showed Id1 tumor cell exp, and 50% showed end Id1 exp. The unexpected Id1 exp difference in tumor cells in PP compared to GP pts predicted clinical outcome. Consistently with other reports end Id1 exp is high in both groups. PP showed higher levels. Conclusions: Id1 exp discriminated GP from PP in our PCa cohort. These novel results highlight Id1 as a prognostic marker in PCa. Whether Id1 exp in the diagnostic biopsy can impact PCa therapeutic decision-making needs further investigation. No significant financial relationships to disclose.

Modalities for Imaging of Prostate Cancer

Prostate cancer is the second most common cause of cancer deaths among males in the United States. Prostate screening by digital rectal examination and prostate-specific antigen has shifted the diagnosis of prostate cancer to lower grade, organ confined disease, adding to overdetection and overtreatment of prostate cancer. The new challenge is in differentiating clinically relevant tumors from ones that may otherwise never have become evident if not for screening. The rapid evolution of imaging modalities and the synthesis of anatomic, functional, and molecular data allow for improved detection and characterization of prostate cancer. However, the appropriate use of imaging is difficult to define, as many controversial studies regarding each of the modalities and their utilities can be found in the literature. Clinical practice patterns have been slow to adopt many of these advances as a result. This review discusses the more established imaging techniques, including Ultrasonography, Magnetic Resonance Imaging, MR Spectroscopy, Computed Tomography, and Positron Emission Tomography. We also review several promising techniques on the horizon, including Dynamic Contrast-Enhanced MRI, Diffuse-Weighted Imaging, Superparamagnetic Nanoparticles, and Radionuclide Scintigraphy.

Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men

Overtreatment of prostate cancer (PCa) is a concern, especially in patients who might qualify for the diagnosis of insignificant prostate cancer (IPCa). The ability to identify IPCa prior to definitive therapy was tested. In a cohort of 1132 men a nomogram was developed to predict the probability of IPCa. Predictors consisted of prostate-specific antigen (PSA), clinical stage, biopsy Gleason sum, core cancer length and percentage of positive biopsy cores (percent positive cores). IPCa was defined as organ-confined PCa (OC) with tumor volume (TV) <0.5 cc and without Gleason 4 or 5 patterns. Finally, an external validation of the most accurate IPCa nomogram was performed in the same group. IPCa was pathologically confirmed in 65 (5.7%) men. The 200 bootstrap-corrected predictive accuracy of the new nomogram was 90% versus 81% for the older nomogram. However, in cutoff-based analyses of patients who were qualified by our and the older nomograms as high probability for IPCa, respectively 63% and 45% harbored aggressive PCa variants at radical prostatectomy (Gleason score 7-10, ECE, SVI, and/or LNI). Despite a high accuracy, currently available models for prediction of IPCa are incorrect in 10% to 20% of predictions. The rate of misclassification is even further inflated when specific cutoffs are used. As a consequence, extreme caution is advised when statistical tools are used to assign the diagnosis of IPCa.

Accuracy of life tables in predicting overall survival in patients after radical prostatectomy

To test the accuracy of life tables (LT), the standard tool for predicting life-expectancy (LE), but the accuracy of which is unknown in patients with prostate cancer, where the 10-year LE is a widely accepted threshold for the delivery of definitive therapy. We tested the accuracy of predictions of LE from LT in 9678 men treated with radical prostatectomy (RP) for prostate cancer. The predictions of LE from LT at 10 years after RP were compared to Kaplan Meier-derived 10-year survival values. Moreover, the accuracy of LT predictions was quantified in a Cox-regression using Harrell's concordance index. To control for the effect of prostate cancer mortality, analyses were repeated in a subset of 5955 patients with no evidence of disease recurrence. Additional stratification schemes were applied to control for age and comorbidity. At RP, the median age was 64 years, the median Charlson Comorbidity Index (CCI) was 1 and the median LT-derived LE was 16 years. The median actuarial survival was not reached (mean 12.4 years). In the whole group the LT-predicted 10-year survival was 96.8%, vs an observed of 75.3%. In men with no disease recurrence the LT-predicted survival was 97.3%, vs 81.1% observed. After age and CCI stratification, LT overestimated the 10-year survival the most in those aged 65-69 years and in patients with CCI scores of >2. The overestimation of LE can lead to overtreatment of prostate cancer, especially in those men who die early from other causes.

Low-risk prostate cancer can and should often be managed with active surveillance and selective delayed intervention

In this Viewpoint article, Professor Klotz argues that active surveillance of patients with low-risk prostate cancer, followed by intervention when pre-specified criteria are fulfilled, is an approach that could prevent unnecessary overtreatment of prostate cancer. Professor Klotz describes patients eligible for this approach, the strategy for active surveillance, and the criteria for intervention.

4004 ORAL Avoiding overtreatment of prostate cancer: optimising patient selection for active surveillance

Inhibition of tumor angiogenesis through simultaneously disturbing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) mediated signaling pathways is a well-established approach in intervention of tumor. A series of 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety were synthesized and evaluated as potent angiokinase inhibitors. Compound 8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing apoptosis. Compound 8a has emerged as a promising lead compound for development of angiokinase inhibitors targeting VEGFR and PDGFR.

PSA density as a predictor of aggressive prostate cancer on repeat prostate biopsy

5007 Background: Prostate biopsy procedures carry a high false-negative rate. However, since Gleason score is strongly associated with cancer-specific mortality; efforts to identify men who harbor high-grade prostate cancer will likely assist in patient selection for repeat biopsies. We sought to identify risk factors for the detection of aggressive prostate cancer (Gleason ≥ 7) on repeat biopsy. Methods: Clinical and pathologic variables collected from subjects undergoing a repeat biopsy included all prostate specific antigen (PSA) values, PSA density (PSAD), PSA doubling time (PSADT). PSADT was examined using PSAs up to the first biopsy, and also in an exploratory analysis using both pre- and post-biopsy PSAs. Predictors of aggressive prostate cancer were identified using recursive partitioning and a stepwise Cox regression model. Results: 511 patients with initial negative biopsies underwent 1,319 biopsy procedures. Median follow-up was 3.7 years. Aggressive cancer was diagnosed in 52 of 511 (10.18%) patients. Recursive partitioning analysis selected PSAD as the sole factor for distinguishing high- and low-risk groups. Based on K-M analysis, a PSAD &lt;= 0.304 ng/ml/cc carried 2 and 5 year aggressive cancer detection rates of 4% (± 1.9%) and 9% (± 3.5%) respectively, whereas a PSAD &gt; 0.304 ng/ml/cc carried cancer detection rates of 23% (± 11.9%) and 36% (±15.3%) at 2 and 5 years (p-value &lt;.0001). Independent prognostic factors included (HR, 95% CI): PSA &gt;= 9.7 (2.565, 1.404 - 4.688), PSAD 0.13 - &lt; 0.19 ng/ml/cc (0.423, 0.179 - 0.999) and volume &gt;= 43.3 cc (0.454, 0.247 - 0.833). PSADT became significant when all PSA data were analyzed: PSADT &lt; 2 years (4.203, 1.894 - 9.325) and PSADT &gt;= 5 years (0.17, 0.89- 0.326). Conclusions: In decision tree analysis, a high PSAD is predictive of aggressive prostate cancer on a repeat biopsy. In addition, high PSA, lower PSAD and prostate volume are predictive of aggressive prostate cancer. However in follow-up using all PSA values, a PSADT &lt; 2 yrs. becomes the most significant predictor of aggressive cancer. Such data may help identify the most appropriate patients for a repeat biopsy and could reduce the rate of unnecessary biopsies and the inherent over-treatment of prostate cancer. No significant financial relationships to disclose.

Incidence of initial local therapy among men with lower-risk prostate cancer in the United States: Miller DC, Gruber SB, Hollenbeck BK, Montie JE, Wei JT, Department of Urology, University of Michigan, Ann Arbor, MI

Background The frequently indolent nature of early-stage prostate cancer in older men and in men with low- or moderate-grade tumors and the demonstration that the survival benefits of radical prostatectomy are primarily among men younger than 65 years have led to concerns about prostate cancer overtreatment. Methods Using data from 13 Surveillance, Epidemiology, and End Results registries, we performed a retrospective cohort study of 71,602 men who were diagnosed with localized or regional prostate cancer between 2000 and 2002. We quantified the incidence of initial curative therapy (i.e., surgery or radiation therapy) among men with lower-risk cancers as defined by their limited likelihood of either dying from expectantly managed prostate cancer or achieving a survival benefit from local therapy. Stratified analyses and multinomial logistic regression models were used to quantify the absolute and relative rates of curative therapy among men in various age-grade strata. All statistical tests were two-sided. Results We identified 24,405 men with lower-risk prostate cancers and complete data for the first course of treatment. Initial curative therapy was undertaken in 13,537 of these men (55%); 81% of treated men received radiation therapy. The likelihood of curative therapy, relative to expectant management, varied statistically significantly among lower-risk age-grade strata (all P Conclusions These data quantify a target population for whom greater use of expectant approaches may reduce overtreatment and improve the quality of localized prostate cancer care.

Incidence of Initial Local Therapy Among Men With Lower-Risk Prostate Cancer in the United States

The frequently indolent nature of early-stage prostate cancer in older men and in men with low- or moderate-grade tumors and the demonstration that the survival benefits of radical prostatectomy are primarily among men younger than 65 years have led to concerns about prostate cancer overtreatment. Using data from 13 Surveillance, Epidemiology, and End Results registries, we performed a retrospective cohort study of 71,602 men who were diagnosed with localized or regional prostate cancer between 2000 and 2002. We quantified the incidence of initial curative therapy (i.e., surgery or radiation therapy) among men with lower-risk cancers as defined by their limited likelihood of either dying from expectantly managed prostate cancer or achieving a survival benefit from local therapy. Stratified analyses and multinomial logistic regression models were used to quantify the absolute and relative rates of curative therapy among men in various age-grade strata. All statistical tests were two-sided. We identified 24,405 men with lower-risk prostate cancers and complete data for the first course of treatment. Initial curative therapy was undertaken in 13,537 of these men (55%); 81% of treated men received radiation therapy. The likelihood of curative therapy, relative to expectant management, varied statistically significantly among lower-risk age-grade strata (all P<.05). Assuming that initial expectant management is appropriate for all lower-risk cancers, 2564 men (10%) in this population-based sample were overtreated with radical prostatectomy and 10,973 (45%) with radiation therapy. These data quantify a target population for whom greater use of expectant approaches may reduce overtreatment and improve the quality of localized prostate cancer care.

Free and total human glandular kallikrein 2 in patients with prostate cancer

Objectives The use of prostate-specific antigen (PSA, hK3) results in the overdiagnosis and overtreatment of prostate cancer. Markers are needed that could identify aggressive, fast-growing tumors and help decide which patients would benefit most from aggressive treatment. Human glandular kallikrein 2 (hK2) could be such a marker. The aim of this study was to test how PSA and hK2 could predict the pathologic stage and grade in a set of patients with clinically organ-confined disease. Methods Heparin plasma was collected from 188 patients who had undergone radical prostatectomy at the Turku University Central Hospital. Total and free PSA, as well as total and free hK2, were measured and the results compared with the pathologic TNM stage, tumor World Health Organization grade, and Gleason score. Results Free and total hK2 performed similarly to PSA in their ability to separate groups of patients with different stages or grades. Concentrations of both kallikreins were significantly different in patients with World Health Organization grade 1 cancer compared with grade 2. Neither marker could separate patients with different Gleason scores. Although PSA concentrations increased most between patients with Stage pT2b and those with pT3a, the increase in hK2 was most pronounced between those with Stage pT3a and those with pT3b. Conclusions Although hK2 could not predict the cancer stage or grade better than PSA, changes in the hK2 and PSA concentrations occurred at different points in cancer progression. hK2 may have a role in the prognosis of prostate cancer, but additional studies with longer follow-up are required to determine whether hK2 can help when selecting treatment options.

Some comments and data on the overtreatment of prostate cancer

Screening and clinical staging of prostate cancer (CaP) do not unequivocally earmark those who should undergo biopsy, nor does biopsy unequivocally distinguish between virulent and benign forms of the disease. The introduction of the prostate-specific antigen (PSA) test has resulted in earlier detection of CaP, a doubling of its incidence rate, and a parallel increase in the number of men treated. However, as shown by Etzioni et al. (1), PSA screening is responsible for a significant level of overdiagnosis, i.e., “the detection of prostate cancer that otherwise would not have been diagnosed within the patient's lifetime.” Earlier detection and overdiagnosis, rather than any radical improvements in surgical and radiotherapeutic techniques, albeit harmoniously applied, have had the effect of presenting us with levels of 10-year cause-specific survival higher than the 5-year survivals for most other cancers.

PSA screening for prostate cancer: The current controversy – a viewpoint

Prostate cancer is an important health problem. Randomized trials have not yet proven whether or not screening with prostate-specific antigen measurements reduces morbidity or mortality. The potential for overtreatment of prostate cancers not destined to cause future mortality, the uncertainty about the benefits of aggressive treatment of screen-detected cancers, and the relatively high costs of prostate cancer screening programs are all areas of concern. A shared approach to decisions about screening individual patients pending better evidence is one strategy for clinicians to consider in dealing with this controversial problem.

Detection of latent prostate cancer from routine screening: Comparison with breast cancer screening

Objectives One criticism of routine prostate cancer screening is the possibility that latent prostate cancer would be detected and treated in men who would otherwise never need treatment for their prostate cancer. This increase in latent cancer detection with screening could lead to overtreatment, with its resulting increases in morbidity, mortality, and health care costs. In contrast, breast cancer screening is widely accepted, and there is little concern about latent breast cancer detection and overtreatment of breast cancer due to screening. This study compares the detection of latent prostate cancer from screening with the detection of latent cancer in an established cancer screening program (breast cancer screening) and examines the risk that screening leads to an increase in detection of latent cancer over traditional methods of detection for both breast and prostate cancer. Methods The present study reviews outcomes data from several large prostate and breast cancer screening trials. The natural history of latent prostate and breast cancer is then reviewed. By applying this information, the rate of latent prostate cancer detection and latent breast cancer detection with screening is compared. Results Recent large-scale prostate cancer screening studies have reported a latent cancer detection rate of 2.9% to 8.0%. This rate of detection is virtually the same as that found by traditional methods of detection. Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer that accounts for 16.2% to 23.7% of breast cancers detected in screening programs using mammography. The literature estimates that DCIS will remain latent in 50% to 66% of patients. These data suggest that the latent breast cancer detection rate in screening programs is 8.1 % to 15.6%, which is a threefold to fivefold increase compared with the detection rate of latent breast cancer prior to screening with mammography. Conclusions These results suggest that the latent prostate cancer detection rate from screening is similar to or less than the latent breast cancer detection rate from screening. Furthermore, prostate cancer screening does not appear to increase the detection rate of latent cancer over traditional methods of detection. This should eliminate concern that prostate cancer screening will lead to overtreatment of prostate cancer.