Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, Part I: Introduction, Risk Assessment, Staging, and Risk-Based Management.

PURPOSE: The summary presented herein represents Part I of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing risk assessment, staging, and risk-based management in patients diagnosed with clinically localized prostate cancer. Please refer to Parts II and III for discussion of principles of active surveillance, surgery and follow-up (Part II), and principles of radiation and future directions (Part III). MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. RESULTS: The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding risk assessment, staging, and risk-based management are detailed herein. CONCLUSIONS: This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

Routine Postoperative Hemoglobin Assessment Poorly PredictsTransfusion Requirement among Patients Undergoing Minimally Invasive Radical Prostatectomy.

INTRODUCTION: An advantage of minimally invasive radical prostatectomy over open surgery is decreased blood loss. At our institution hemoglobin is routinely checked 4 and 14 hours postoperatively. We assessed the relevance of this practice in a contemporary cohort undergoing minimally invasive radical prostatectomy. METHODS: We retrospectively reviewed data from patients undergoing laparoscopic or robotic radical prostatectomy at our institution between January 2010 and September 2018. We identified 3,631 patients with preoperative and postoperative hemoglobin values, and assessed the role of routine hemoglobin assessment in determining need for transfusion within 30 days. Medicare reimbursement rates for 2019 were used for cost analysis. RESULTS: Of 3,631 patients in our cohort 44 (1.2%) required transfusion. At 4 hours following surgery the median hemoglobin decrease was 8.0% (IQR 4.8 to 11.4) for patients who did not receive transfusion and 12.5% (9.5 to 19.2) for those who received transfusion. At 14 hours the median decrease was 14.2% (IQR 10.0 to 18.4) vs 33.1% (22.6 to 38.6). Routine hemoglobin assessment had no role in the decision to transfuse in 18 patients (41%). No patient was transfused based on 4-hour values alone. Omitting 1 hemoglobin assessment could have resulted in institutional savings of $37,000 during this period. CONCLUSIONS: As transfusion following minimally invasive radical prostatectomy is rare, scheduled postoperative hemoglobin assessments in the absence of symptoms are unnecessary to recognize bleeding events. The largest hemoglobin difference between men who did vs did not receive transfusion was seen at 14 hours postoperatively. Thus, this single hemoglobin evaluation is sufficient.

An assessment of Prostate Cancer Research International: Active Surveillance (PRIAS) criteria for active surveillance of clinically low-risk prostate cancer patients.

INTRODUCTION: Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients. METHODS: A D'Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts. RESULTS: The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49-0.75), pT3 (OR 0.41; 95% CI 0.31-0.55), nodal metastases (OR 0.37; 95% CI 0.10-1.31), or any adverse feature (OR 0.56; 95% CI 0.45-0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46-1.09 and survival HR 0.72; 95% CI 0.36-1.47). CONCLUSIONS: Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria.

A case-mix-adjusted comparison of early oncological outcomes of open and robotic prostatectomy performed by experienced high volume surgeons.

OBJECTIVE: To compare early oncological outcomes of robot assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) performed by high volume surgeons in a contemporary cohort. METHODS: We reviewed patients who underwent radical prostatectomy for prostate cancer by high volume surgeons performing RALP or ORP. Biochemical recurrence (BCR) was defined as PSA ≥ 0.1 ng/mL or PSA ≥ 0.05 ng/mL with receipt of additional therapy. A Cox regression model was used to evaluate the association between surgical approach and BCR using a predictive model (nomogram) based on preoperative stage, grade, volume of disease and PSA. To explore the impact of differences between surgeons, multivariable analyses were repeated using surgeon in place of approach. RESULTS: Of 1454 patients included, 961 (66%) underwent ORP and 493 (34%) RALP and there were no important differences in cancer characteristics by group. Overall, 68% of patients met National Comprehensive Cancer Network (NCCN) criteria for intermediate or high risk disease and 9% had lymph node involvement. Positive margin rates were 15% for both open and robotic groups. In a multivariate model adjusting for preoperative risk there was no significant difference in BCR rates for RALP compared with ORP (hazard ratio 0.88; 95% CI 0.56-1.39; P = 0.6). The interaction term between nomogram risk and procedure type was not statistically significant. Using NCCN risk group as the covariate in a Cox model gave similar results (hazard ratio 0.74; 95% CI 0.47-1.17; P = 0.2). The interaction term between NCCN risk and procedure type was also non-significant. Differences in BCR rates between techniques (4.1% vs 3.3% adjusted risk at 2 years) were smaller than those between surgeons (2.5% to 4.8% adjusted risk at 2 years). CONCLUSIONS: In this relatively high risk cohort of patients undergoing radical prostatectomy we found no evidence to suggest that ORP resulted in better early oncological outcomes then RALP. Oncological outcome after radical prostatectomy may be driven more by surgeon factors than surgical approach.

Costs of medical care after open or minimally invasive prostate cancer surgery: a population-based analysis.

BACKGROUND: Evidence suggests that minimally invasive radical prostatectomy (MRP) and open radical prostatectomy (ORP) have similar short-term clinical and functional outcomes. MRP with robotic assistance is generally more expensive than ORP, but it is not clear whether subsequent costs of care vary by approach. METHODS: In the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked with Medicare claims, men aged 66 years or older who received MRP or ORP in 2003 through 2006 for prostate cancer were identified. Total cost of care was estimated as the sum of Medicare payments from all claims for hospital care, outpatient care, physician services, home health and hospice care, and durable medical equipment in the first year from the date of surgical admission. The impact of surgical approach on costs was estimated, controlling for patient and disease characteristics. RESULTS: Of 5445 surgically treated prostate cancer patients, 4454 (82%) had ORP and 991 (18%) had MRP. Mean total first-year costs were more than $1200 greater for MRP compared with ORP ($16,919 vs $15,692; P = .08). Controlling for patient and disease characteristics, MRP was associated with 2% greater mean total payments, but this difference was not statistically significant. First-year costs were greater for men who were older, black, lived in the Northeast, had lymph node involvement, more advanced tumor stage, or greater comorbidity. CONCLUSIONS: In this population-based cohort of older men, MRP and ORP had similar economic outcomes. From a payer's perspective, any benefits associated with MRP may not translate to net savings compared with ORP in the first year after surgery.

Validation study of a web-based assessment of functional recovery after radical prostatectomy.

BACKGROUND: Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. METHODS: We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. RESULTS: Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. CONCLUSIONS: We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice.

Critical elements in fellowship training.

In this article, we present the critical elements of fellowship training for the urologic oncologist. As an example, the Memorial Sloan-Kettering Cancer Center experience is outlined in detail, including the clinical experience, research curriculum, laparoscopic and minimally invasive exposure, and didactic lecture series.

Radical prostatectomy for clinically localized, high risk prostate cancer: critical analysis of risk assessment methods.

PURPOSE: Standardized criteria are lacking to define high risk, clinically localized prostate cancer before definitive treatment. Reliance on simple risk stratification schemes to define high risk cancers has led many physicians and patients toward therapeutic nihilism, inappropriately selecting androgen deprivation instead of definitive local therapy. Of patients undergoing radical prostatectomy we identified those at high risk based on 8 previously described definitions. We examined pathological characteristics and prostate specific antigen outcomes. MATERIALS AND METHODS: The study population included 4,708 men treated with radical prostatectomy alone between 1985 and 2004. Estimates of prostate specific antigen relapse for patients at high risk were generated with the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the HR for recurrence in high risk vs nonhigh risk cohorts. RESULTS: Depending on the definition used patients at high risk composed 3% to 38% of the study population. The proportion of patients with extracapsular extension, seminal vesicle invasion and lymph node metastasis among men with high risk cancer was 35% to 71%, 10% to 33% and 7% to 23%, respectively. Of the high risk tumors 22% to 63% proved to be confined to the prostate pathologically. While patients at high risk had a 1.8 to 4.8-fold increased hazard of prostate specific antigen relapse, their 5-year relapse-free probability after radical prostatectomy alone was 49% (95% CI 39 to 58) to 80% (95% CI 77 to 83). Of patients at high risk who had relapse 25% across all definitions experienced relapse more than 2 years after surgery and in 26% to 39% prostate specific antigen doubling time at recurrence was 10 months or greater. CONCLUSIONS: Patients diagnosed with high risk cancer by currently available definitions do not have a uniformly poor prognosis after radical prostatectomy. Many cancers classified clinically as high risk are actually confined to the prostate pathologically. The risk of extraprostatic disease and prostate specific antigen relapse varies greatly depending on the definition used.

Locally ablative therapies for primary radiation failures: a review and critical assessment of the efficacy.

A significant number of men with prostate cancer will experience biochemical failure following treatment with primary radiation therapy. For patients with biopsy-proven recurrent cancer confined to the prostate, local salvage therapy may be a potentially curative treatment option. Most men, however, do not undergo local salvage therapy owing to difficulties in diagnosis as well as concerns over treatment-related complications in the salvage setting. Recently, improvements in technique and technology have substantially reduced the morbidity associated with locally ablative therapies, resulting in an increased interest in the use of minimally invasive therapies such as brachytherapy, cryotherapy, and high-intensity focused ultrasound in the salvage setting. Although these treatments are well tolerated, concerns remain over incomplete and inadequate treatment with locally ablative therapies. Future studies are required to appropriately select candidates for salvage ablative therapies and to determine the long-term oncologic efficacy of these treatments.

Risk assessment for biochemical recurrence prior to radical prostatectomy: significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA-elevation in serum.

Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate-specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate-specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this "base" model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA < or = 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA < or = 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap-corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA-elevation (tPSA < or = 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756-0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for "moderately elevated" PSA. For patients with a moderate tPSA-elevation (tPSA < or = 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR-prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR.

Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients.

OBJECTIVES: To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables. METHODS: We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records. RESULTS: In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P < 0.001). CONCLUSIONS: The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.

Achieving optimal outcomes after radical prostatectomy.

PURPOSE: The most favorable outcome that can be achieved after radical prostatectomy is complete tumor resection without recurrence and full recovery of continence and potency. Risks of erectile dysfunction, incontinence, and disease recurrence are well described, but in isolation, do not adequately inform patients of the possibility of becoming cancer-free while at the same time returning to their preoperative functional state. We sought to determine the frequency of optimal outcomes after radical prostatectomy and the time to such outcomes. PATIENTS AND METHODS: Patients who underwent radical prostatectomy performed at a tertiary referral center between July 1998 and July 2003 for clinical stage T1 to T3 prostate cancer were identified. Patients were excluded if they were incontinent or impotent preoperatively, or if they had received radiotherapy or neoadjuvant androgen deprivation therapy previously. Six hundred forty-seven patients were analyzed for time to recovery of full continence and potency without cancer recurrence after surgery. Optimal outcome probability was calculated with a Markov state transition model to simulate clinical outcomes in the first 4 years following radical prostatectomy. RESULTS: Mean patient age was 58 years, and mean pretreatment prostate-specific antigen was 6.9 ng/mL. Cancer-free status with full continence and potency was achieved in 30% of men at 12 months, 42% at 24 months, 47% at 36 months, and 53% at 48 months postoperatively. CONCLUSION: Optimal outcomes after radical prostatectomy can be achieved in a small majority of cases. Time to full recovery is primarily dictated by recovery of erectile function. This information is helpful for patients interested in their chances of returning to their preoperative functional state.