Prostate Cancer Screening and Young Black Men: Can Early Communication Avoid Later Health Disparities?

This study aims to determine if younger men, across racial and ethnic groups, discussed the benefits/risks/harms of PSA screening with health care professionals. Publicly available data were obtained from the Health Information National Trends Survey https://hints.cancer.gov/ in March 2019. Cross-sectional analysis of 518 men between the ages of 18 and 49 years from men who completed the survey between October 2011 and February 2012 (HINTS cycle 4) was performed. We used logistic regression to evaluate the association between race/ethnicity and discussions around PSA. Less than 10% of the participants reported a prior PSA; Black and Hispanic men were more likely compared with White men. Compared with White men, Black and other race men reported receiving less communications from some doctors recommending PSA screening (ORblack: 0.16, 95% CIblack: 0.07-0.38; ORother: 0.10, 95% CIother: 0.04-0.25), and that no one is sure PSA testing saves lives (ORblack: 0.49, 95% CIblack: 0.04-6.91; ORother: 0.17, 95% CIother: 0.06-0.48). Minority men, while more likely to have had a PSA, were less likely to be told of the harms and benefits of PSA testing, compared with White men. Increasing communication surrounding screening advantages and disadvantages between providers and patients can increase awareness and knowledge among younger men. In a post-COVID-19 environment, communication regarding the return to preventative screenings within vulnerable populations is an important message to convey. Research shows preventive screenings have dropped across all population groups due to the pandemic yet the decline disproportionately affects Black and other minority men.

Observed racial disparity in the negative predictive value of multi-parametric MRI for the diagnosis for prostate cancer.

OBJECTIVE: To evaluate the trend that despite recent advances in the screening, diagnosis, and management of prostate cancer (PCa), African-Americans (AAs) continue to have poorer outcomes compared to their Caucasian (CAU) counterparts. The reason for this may be rooted in biological differences in the cancer between the two groups; however, there may be some inherent disparities within the efficacy of the screening modalities. In this study, we aim to evaluate the negative predictive value (NPV) of multi-parametric MRI (mpMRI) between AA compared to CAUs. METHODS: All mpMRI between January 2014 and June 2017 were evaluated. The MRIs were read by dedicated genitourinary radiologists. Subsequently, the readings were correlated to final pathology after the patients underwent radical prostatectomy. The NPV and negative likelihood ratios (-LR) of mpMRI were evaluated in AAs versus CAUs based on four cutoffs (≥ Grade I, ≥ Grade II, ≥ Grade III and ≥ Grade IV). RESULTS: The mpMRI was almost equally as effective between AAs and CAUs in excluding Grade III (NPV = 89 and 94, respectively), and Grade IV or above (NPV = 96 and 98, respectively) PCa; however, the NPV of mpMRI was significantly lower for Grade I (NPV = 32 and 52, respectively) and Grade II (NPV = 50 and 79, respectively) PCa. CONCLUSION: Despite advances in the screening for PCa, there are disparities noted in the efficacy of screening tools between AAs and CAUs. For this reason, patients should be risk stratified and their screening results should be evaluated with consideration given to their baseline risk.

Surgical trends and patient factors associated with the treatment of apical pelvic organ prolapse from a national sample.

INTRODUCTION AND HYPOTHESIS: Prolapse of the vaginal apex can be treated using multiple surgical modalities. We describe national trends and patient characteristics associated with the surgical approach and compare perioperative outcomes of abdominal versus vaginal repair of apical pelvic organ prolapse (POP). METHODS: The 2006-2012 National Surgical Quality Improvement Program Database was queried for abdominal sacrocolpopexy (ASC) and vaginal apical suspensions. Patients were stratified by whether or not concomitant hysterectomy (CH) was performed or whether or not they were post-hysterectomy (PH). Multivariate logistic regressions were adjusted for confounding variables. RESULTS: A total of 6,147 patients underwent apical POP repair: 33.9% (2,085) ASCs, 66.1% (4,062) vaginal suspensions. 60.0% (3,689) underwent CH. In all cohorts, older patients were less likely to have ASC (CH: OR 0.48, CI 0.28-0.83, p = 0.008 for age ≥ 60; PH: OR 0.28, CI 0.18-0.43, p < 0.001). Over time, the proportion of all vaginal and abdominal repairs remained relatively stable. Use of minimally invasive ASC, however, increased over the study period (trend p < 0.001), and use of mesh for vaginal suspensions decreased (p < 0.001). ASC had a longer median operative time (PH 174 vs 95 min, p < 0.001; CH 192 vs 127 min, p < 0.001). Complication rates were the same for vaginal repairs and ASC, overall and when sub-stratified by hysterectomy status. CONCLUSIONS: Nationally, most apical POP repairs are performed via a vaginal route. Older age was predictive of the vaginal route for both CH and PH groups. ASCs had longer operative times. There has been increased utilization of minimally invasive ASC and decreased use of mesh-augmented vaginal suspensions over time.

Outcomes of minimally invasive abdominal sacrocolpopexy with resident operative involvement.

INTRODUCTION AND HYPOTHESIS: Resident involvement in complex surgeries is under scrutiny with increasing attention paid to health care efficiency and quality. Outcomes of urogynecological surgery with resident involvement are poorly described. We hypothesized that resident surgical involvement does not influence perioperative outcomes in minimally invasive abdominal sacrocolpopexy (ASC). METHODS: Using the 2006-2012 National Surgical Quality Improvement Program database, we identified 450 cases of laparoscopic or robotic ASC performed with resident involvement. Resident operative participation was stratified by experience (junior [PGY 1-3] vs senior level [PGY ≥4]). The primary outcome was operative time, and multinomial logistic regression was used to determine the effects of resident involvement and experience. Chi-squared analyses were used to assess the relationship between resident participation with length of stay (LOS) and 30-day complications and readmissions. RESULTS: Residents participated in 74% (n = 334) of these surgeries, and these cases were significantly longer (median 220 vs 195 min, p = 0.03). On multivariate analysis, senior level resident involvement was associated with longer operative times across all time intervals compared with <2 h (2 to ≤4 h relative risk reduction [RRR] 4.1, p = 0.007, CI 1.47-11.40; 4 to ≤6 h RRR 6.6, p = 0.001, CI 2.23-19.44; ≥6 h RRR 4.7, p = 0.020, CI 1.28-17.43). Resident participation was not associated with LOS, readmissions, or complications. CONCLUSIONS: Senior level resident involvement in minimally invasive ASC is associated with longer operative times, with no association with LOS or adverse perioperative outcomes. The educational benefit of surgical training does not adversely affect patient outcomes for ASC.

National Surgical Trends and Perioperative Outcomes of Midurethral Sling Placement for Stress Urinary Incontinence.

OBJECTIVE: To determine contemporary trends, patient characteristics, and outcomes for midurethral sling placement (MUS) at inpatient and ambulatory facilities from a national database. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified 7767 women who underwent isolated MUS 2006-2012. We stratified patients by hospitalization type (outpatient vs hospitalization). Primary outcomes were 30-day complications, readmissions, and reoperations. Multivariable logistic regression was used to determine patient and surgery factors associated with adverse perioperative outcomes. RESULTS: Among the 7767 women undergoing MUS, 84.3% underwent outpatient surgery (n = 6547), with greater use of outpatient facilities over time (P < .001). Overall, 3.9% of patients (n = 300) experienced one or more postoperative complications. Complications were more likely among inpatients (7.4% vs 3.2%; odds ratio [OR] 0.48, confidence interval [CI] 0.36-0.64, P < .001), with gynecologists as compared to urologists (4.4% vs 3.1%; OR 1.53, CI 1.16-2.02, P = .003), and with resident participation (5.1% vs 3.7%; OR 1.32, CI 1.01-1.73, P = .04). On multivariable analysis, outpatients were less likely to experience readmissions (0.9% vs 2.8%; OR 0.2, CI 0.09-0.56, P = .002) or undergo reoperation (0.3% vs 3.1%; OR 0.10, CI 0.02-0.38, P = .001). CONCLUSION: Use of outpatient surgical centers for MUS is increasing, with lower rates of complications, readmissions, and reoperations compared to inpatient treatment. Although there is a difference in complications by specialty and with resident involvement, overall incidence of complications is low.

Suppression of antiviral innate immunity by sunitinib enhances oncolytic virotherapy.

The use of lytic viruses to preferentially infect and eliminate cancer cells while sparing normal cells is a promising experimental therapeutic approach for treating cancer. However, the efficacy of oncolytic virotherapy is often limited by two innate immunity pathways, the protein kinase PKR and the 2'-5'-oligoadenylate (OAS)/RNase L systems, which are widely present in many but not all tumor cell types. Previously, we reported that the anticancer drug, sunitinib, an inhibitor of VEGF-R and PDGF-R, has off-target effects against both PKR and RNase L. Here we show that combining sunitinib treatments with infection by an oncolytic virus, vesicular stomatitis virus (VSV), led to the elimination of prostate, breast, and kidney malignant tumors in mice. In contrast, either virus or sunitinib alone slowed tumor progression but did not eliminate tumors. In prostate tumors excised from treated mice, sunitinib decreased levels of the phosphorylated form of translation initiation factor, eIF2-α, a substrate of PKR, by 10-fold while increasing median viral titers by 23-fold. The sunitinib/VSV regimen caused complete and sustained tumor regression in both immunodeficient and immunocompetent animals. Results indicate that transient inhibition of innate immunity with sunitinib enhances oncolytic virotherapy allowing the recovery of tumor-bearing animals.

The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer.

INTRODUCTION: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. METHODS: Data from the REDUCE trial was used to identify predictive factors for 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) and calibration plots. RESULTS: A total of 18 nomograms assessing the risks of cancer, high grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), erectile dysfunction (ED), acute urinary retention (AUR), gynecomastia, urinary tract infection (UTI) and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. CONCLUSIONS: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision-making that is accessible, intuitive, and clinically relevant.

Formalized prediction of clinically significant prostate cancer: is it possible?

Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.

Role of postchemotherapy retroperitoneal lymph node dissection in advanced germ cell tumors.

Advanced germ cell tumors (GCTs) are curable with the appropriate integration of cisplatin-based chemotherapy and postchemotherapy surgical resection of residual masses. For men with retroperitoneal metastases, postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is a vital component of this treatment algorithm. The rationale for PC-RPLND is based on the consistent 10% to 20% and 35% to 55% incidence of viable malignancy and teratoma, respectively. Prognostic factors and nomograms cannot predict the presence of necrosis with sufficient accuracy to obviate the need for PC-RPLND. This article reviews the indications, technique, and outcomes of PC-RPLND in the management of advanced GCT.

Focal therapy in the management of localized prostate cancer.

OBJECTIVES: • To assess the rationale, efficacy, and morbidity of various methods of achieving focal prostatic ablation. • To determine the current role of focal therapy in the management of localized prostate cancer. METHODS: • We performed a literature review of focal therapy in prostate cancer, with an emphasis on more established methods such as cryoablation and high-intensity focused ultrasound. RESULTS AND CONCLUSIONS: • Focal ablative methods allow targeted destruction of prostatic tissue while limiting the morbidity associated with whole-gland therapy. • Local cancer control after focal therapy appears promising but does not approach that of established whole-gland therapies. • Until we have the ability to identify patients reliably with truly focal disease and predict their natural history, focal therapy cannot be considered to be the definitive therapy for localized prostate cancer.

Racial disparities in urologic health care.

In the United States, disparities in health care delivery and access are apparent between different racial and ethnic groups. Minorities, including African Americans, often suffer disproportionately from disease compared to Caucasians. In the urologic arena, this is apparent in urologic cancer screening, treatment choices, and survival, as well as in the arena of chronic kidney disease, transplant allocation, and transplant outcomes. Latino men also seem to be affected more often by erectile dysfunction than Caucasian counterparts. Disparities such as these have been identified as a problem in the delivery of health care in the United States, and resources have been allocated to help allay the disparity. Through organizations such as the Cleveland Clinic Minority Men's Health Center, policy initiatives, and increased cultural awareness by physicians, steps can be made to reduce and eliminate health care disparities.

Are nomograms needed in the management of bladder cancer?

Bladder cancer has a remarkably variable natural history. Noninvasive, low-grade (TaLG) lesions have a propensity to recur but pose little threat to the patient's longevity. Non-muscle-invasive, high-grade (Ta-TIS-T1HG) lesions can be effectively treated with intravesical BCG, but a subset may progress to muscle-invasive and metastatic bladder cancer. Muscle-invasive cancers (T2-T3) are uniformly lethal if inadequately treated, and subsets of patients benefit from perioperative chemotherapy and some may be adequately treated with bladder preservation strategies. The ability to accurately predict this variable natural history is essential to optimize treatment. At each stage of disease, the prognosis is often influenced by multiple parameters (e.g., tumor grade and stage, age, comorbidity) and treatments (e.g., radical cystectomy vs. BCG), and different endpoints are relevant based on the stage of disease (recurrence for TaLG, progression for Ta-TIS-T1HG, survival for T2-T4a). Historically, prediction of these endpoints for decision-making has been accomplished with physician judgment and/or basic decision aids such as risk classification systems. However, such methods of risk estimation are unable to fully account for the complex tumor biology and behavior of bladder cancer, potentially leading to inaccurate predictions and inappropriate treatment assignment. Nomograms are capable of incorporating multiple variables and generating accurate risk estimates tailored to the individual patient which may greatly facilitate patient counseling and treatment selection. Although their use has become more widespread, bladder cancer nomograms remain a relatively nascent field of study, and further development of novel nomograms that can account for all clinical stages of bladder cancer is needed.

Defining the optimal treatment for clinical stage I nonseminomatous germ cell testicular cancer using decision analysis.

PURPOSE There is equipoise regarding the optimal treatment of clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT). Formal mechanisms that enable patients to consider cancer outcomes, treatment-related morbidity, and personal preferences are needed to facilitate decision making between retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and surveillance. METHODS Decision analysis was performed using a Markov model that incorporated likelihoods of survival, treatment-related morbidity, and utilities for seven undesired post-treatment health states to estimate the quality-adjusted survival (QAS) for each treatment option. Utilities were obtained from 24 hypothetical NSGCT patients using a visual analog (rating) scale and standard gamble. Results Overall, QAS associated with each treatment was high and differences in QAS were small. Surveillance was the preferred intervention for patients with a risk of relapse less than 33% and 37% using the rating scale and standard-gamble method of utility assessment, respectively. Active treatment was favored over surveillance for patients with relapse risk on surveillance greater than 33% and 37% by the rating scale (RPLND preferred) and standard-gamble methods (primary chemotherapy preferred), respectively. Substantial differences in average utilities were seen depending on the method used. By the rating scale, patients substantially devalued life in six of seven undesired health states but they were surprisingly tolerant of treatment-related morbidity using standard gamble. CONCLUSION A decision model has been developed for CS I NSGCT that estimates QAS for RPLND, primary chemotherapy, and surveillance by considering cancer outcomes, morbidity, and patient preferences. Surveillance was the preferred intervention for all except those patients at high risk for relapse.

Performance of prostate cancer prevention trial risk calculator in a contemporary cohort screened for prostate cancer and diagnosed by extended prostate biopsy.

PURPOSE: Statistical models such as the Prostate Cancer Prevention Trial risk calculator have been developed to estimate the cancer risk in an individual and help determine indications for biopsy. We assessed risk calculator performance in a large contemporary cohort of patients sampled by extended biopsy schemes. MATERIALS AND METHODS: The validation cohort comprised 3,482 men who underwent a total of 4,515 prostate biopsies. Calculator performance was evaluated by ROC AUC and calibration plots. A multivariate regression model was fitted to address important predictor variables in the validation data set. Prediction error was calculated as the response variable in another multivariate regression model. RESULTS: Using an average of 13 cores per biopsy prostate cancer was detected in 1,862 patients. The calculator showed an AUC of 0.57 to predict all cancers and 0.60 for high grade cancer. Multivariate analysis of the predictive ability of various clinical factors revealed that race and the number of biopsy cores did not predict overall or high grade cancer at biopsy. Prior negative biopsy, patient age and free prostate specific antigen were significantly associated with prediction error for overall and high grade cancer. Race and family history had a significant association with prediction error only for high grade disease. CONCLUSIONS: To our knowledge our external validation of the Prostate Cancer Prevention Trial risk calculator was done in the largest cohort of men screened for prostate cancer to date. Results suggest that the current calculator remains predictive but does not maintain initial accuracy in contemporary patients sampled by more extensive biopsy schemes. Data suggest that the predictive ability of the calculator in current clinical practice may be improved by modeling contemporary data and/or incorporating additional prognostic variables.

Complications of open primary and post-chemotherapy retroperitoneal lymph node dissection for testicular cancer.

OBJECTIVE: Treatment decisions regarding the use of retroperitoneal lymph node dissection (RPLND) for low-stage and advanced testicular cancer may be influenced by the morbidity of the procedure. We sought to compare the complication profile of primary (P-) and post-chemotherapy (PC-) RPLND using a standardized complication grading scale. MATERIALS AND METHODS: A retrospective analysis was conducted of 112 and 96 patients who underwent P-RPLND and PC-RPLND, respectively, between 1982 and 2007 for perioperative outcomes and late complications. Postoperative complications were graded using a 5-tiered scale based on the severity and/or level of intervention required for resolution. RESULTS: P-RPLND patients had rates of 5%, 24%, and 7% for intraoperative, postoperative, and late complications, respectively. For PC-RPLND, these rates were 12%, 32%, and 7%, respectively (P = 0.11, 0.19, and 1, respectively). Major postoperative complications (grades III-V) were observed in 3 (3%) P-RPLND and 8 (8%) PC-RPLND patients (P = 0.15), including 1 fatal pulmonary embolus in a PC-RPLND patient. Ileus accounted for 63% and 45% of postoperative complications of P-RPLND and PC-RPLND, respectively. PC-RPLND was associated with significantly greater operative times, blood loss, and transfusion rates (P < 0.001). Compared with PC-RPLND after first-line chemotherapy for advanced NSGCT, there were no significant differences in perioperative outcomes for PC-RPLND performed in other settings. CONCLUSIONS: P-RPLND and PC-RPLND are associated with low rates of serious short- and long-term complications and negligible mortality, without significant differences between the 2 procedures. The safe morbidity profile of RPLND performed by fellowship-trained urologic oncologists should be considered during treatment decision-making for low-stage and advanced testicular cancer.

The current state of brachytherapy nomograms for patients with clinically localized prostate cancer.

For men diagnosed with clinically localized prostate cancer, definitive therapy with radical prostatectomy, external beam radiation therapy, or brachytherapy offers a high chance of cure. Currently, there are insufficient data to recommend 1 treatment approach over another, leaving physicians and patients to decide based on their own biases and preferences. Prediction tools, such as nomograms and probability tables, have been created as decision aids to facilitate patient counseling and decision making. Nomograms in particular can assess the therapeutic efficacy of a given therapy by providing individualized estimates of the risk of failure after treatment. The authors performed a comprehensive literature review to identify nomograms assessing the efficacy of brachytherapy in patients with clinically localized prostate cancer, and found a paucity of such models. Analysis of currently available brachytherapy nomograms reveals suboptimal predictive power compared with models based on other treatment modalities. The purpose of this review is to spur development of new and more accurate prediction tools for predicting outcomes after brachytherapy, offering physicians and patients the opportunity to equally assess the efficacy of all available treatment modalities for clinically localized prostate cancer. Cancer 2009;115(13 suppl):3121-7. (c) 2009 American Cancer Society.

Development of a prostate cancer metagram: a solution to the dilemma of which prediction tool to use in patient counseling.

Many treatment options are available to the human with clinically localized prostate cancer, including surgery, radiation, and even active surveillance. To the authors' knowledge, there is no consensus on the optimal management of this patient population, with most clinicians tending to recommend the treatment with which they are most familiar. Effective patient counseling allowing informed decision making can be best achieved with a formalized system that offers accurate predictions of outcomes for all available treatment approaches. The authors organized the currently available prostate cancer prediction tools toward the formation of a metagram that can be used to tailor management to the individual patient. A comprehensive review of the literature was performed to identify published prediction tools intended for use in prostate cancer. Tools were categorized by a combination of treatment modality and the outcome being predicted, and incorporated into a metagram constructed of 16 different treatment options and 10 outcomes related to cancer control, survival, and morbidity. A search of the literature revealed 44 prostate cancer prediction tools that assessed at least 1 of the 160 treatment/outcome combinations that comprise the metagram. Only 31 cells of the metagram were populated with currently available tools. Prediction tools offer the most accurate estimates of outcomes in prostate cancer, but their current role in patient counseling is complicated by the large number of existing tools, as well as a lack of comparative data. To address this, the authors incorporated the most relevant prediction tools currently available into a prostate cancer metagram that may offer evidence-based and individualized predictions for multiple endpoints after all available treatment options in clinically localized prostate cancer. The metagram also reveals areas of deficiency in the current catalog of prediction tools. Many more prediction tools are needed. Cancer 2009;115(13 suppl):3039-45. (c) 2009 American Cancer Society.

Prognostic significance of nondiagnostic molecular changes in urine detected by UroVysion fluorescence in situ hybridization during surveillance for bladder cancer.

OBJECTIVES: To determine the outcomes for patients with nondiagnostic fluorescence in situ hybridization (FISH) (ie, < 4 gains of chromosomes 3, 7, or 17 in < or = 3 cells). FISH detects urothelial carcinoma and is especially beneficial in patients with negative or atypical urine cytology findings. A positive result is defined as a gain of > or = 2 chromosomes (3, 7, or 17) in 4 cells, isolated loss of 9p21 in 12 cells, or isolated gains of only 1 chromosome in > or = 10% of cells. Most FISH-positive patients will develop recurrent urothelial carcinoma within 1 year. METHODS: We compared the data from 149 patients with a nondiagnostic FISH result and > or = 30 months of follow-up with the data from patients with a negative FISH result from the same period. The time to conversion to a positive FISH result or the development of a bladder tumor was recorded. RESULTS: Patients with nondiagnostic FISH results had significantly greater rates of progression to positive FISH findings or the development of a bladder tumor than did patients with negative FISH findings. Most progression occurred within 1 year. Patients with nondiagnostic FISH results and concurrent negative cytology and cystoscopy had a very low risk of developing recurrent disease, similar to that found with truly negative FISH results. CONCLUSIONS: Nondiagnostic FISH results are related to a greater risk of progression to positive FISH results and tumor recurrence than those with negative FISH findings. However, after controlling for negative cytologic and cystoscopic status, a nondiagnostic FISH result does not appear to be an independent predictor of disease recurrence, and aggressive investigation is not warranted.

The specific definition of high risk prostate cancer has minimal impact on biochemical relapse-free survival.

PURPOSE: Accurate categorization of high risk prostate cancer cases remains elusive. Various schemes based on clincopathological criteria have been proposed to stratify cases by presumed recurrence risk. We determined whether survival outcomes are dependent on the specific definition. MATERIALS AND METHODS: The study population included men who underwent radical prostatectomy from 1987 to 1995 (708) and 1996 to 2007 (3,351). Patients who received adjuvant therapy or had no postoperative prostate specific antigen were excluded from analysis. High risk patients were identified based on 6 commonly used definitions. Biochemical failure was defined as a prostate specific antigen of 0.4 ng/ml or greater and increasing or initiation of salvage therapy. Estimates of biochemical relapse-free survival were generated with the Kaplan-Meier method. Hazard ratios for disease recurrence were estimated using Cox proportional hazards analysis. RESULTS: High risk patients determined by the 6 definitions demonstrated a 2.7 to 5.3-fold increased hazard of biochemical relapse, and 5 and 10-year biochemical relapse-free survival rates were 36% to 58% and 25% to 43%, respectively. When stratified by date of treatment high risk patients from 1987 to 1995 generally had worse biochemical relapse-free survival compared to those treated after 1996. Within each era the variation in biochemical relapse-free survival among various high risk definitions was not substantial. CONCLUSIONS: Biochemical relapse-free survival after radical prostatectomy does not vary substantially based on the specific definition of high risk prostate cancer. There is a trend toward improved biochemical relapse-free survival in patients treated more recently, perhaps reflecting stage migration or changes in surgical technique. The data suggest that high risk prostate cancer may represent a relatively homogeneous population.