The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Focal therapy for prostate cancer: what is really needed to move from investigational to valid therapeutic alternative?-a narrative review.

Background and Objective: The most widely accepted therapeutic alternatives for men with intermediate risk prostate cancer (PCa) are mainly represented by whole gland therapies such as surgery or radiotherapy. However, these treatments can carry in some cases profound functional side effects. With the improvement of risk assessment tools and imaging modalities, in particular with the introduction of multiparametric magnetic resonance imaging of the prostate, a fine topographic characterisation of PCa lesions within the prostatic gland is now possible. This has allowed the development of gland-sparing therapies such as focal therapy (FT) as a means to provide an even more tailored approach in order to safely reduce, where feasible, the harms carried by whole gland therapies. Unfortunately, adoption of FT has been considered so far investigational due to some unsolved issues that currently hamper the use of FT as a valid alternative. Here, we aim to identify the main aspects needed to move FT forward from investigational to a valid therapeutic alternative for clinically localized PCa. Methods: The literature discussing the evolution of focal therapy in the years and its current landscape was broadly searched to identify the factors hindering FT adoption and possible solutions. Key Content and Findings: There are three broad areas hindering FT as a valid therapeutic alternative: (I) Correct patient selection; (II) harmonising the different FT technologies; (III) the lack of oncological outcomes. Conclusions: By targeting the three aforementioned weaknesses of FT, greater adoption is expected, finally making FT a valid therapeutic alternative, potentially reshaping prostate cancer treatment and functional outcomes.

Rates of metastatic prostate cancer in newly diagnosed patients: Numbers needed to image according to risk level.

BACKGROUND: The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown. METHODS: Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed. RESULTS: Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1a-c ), 8920 (4.9%) harbored M1a-c stage: 50 (0.07%), 45 (0.1%), 161 (0.5%), 1290 (5.1%), and 7374 (22.0%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk. These resulted in NNI of 1347, 602, 174, 20, and 5, respectively. CONCLUSIONS: Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Prostate-specific Membrane Antigen Imaging in Clinical Guidelines: European Association of Urology, National Comprehensive Cancer Network, and Beyond.

Prostate-specific membrane antigen (PSMA) imaging is characterized by superior accuracy compared to conventional imaging for identification of nodal and distant metastases in prostate cancer. The majority of international clinical guidelines recommend PSMA positron emission tomography/computed tomography for patients experiencing biochemical recurrence, even at low prostate-specific antigen values, to identify candidates for salvage therapies. However, its use in for primary staging is still not recommended.

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer. Design, Setting, and Participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019. Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy. Main Outcomes and Measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts. Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782). Conclusions and Relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

Salvage Lymph Node Dissection for Nodal Recurrent Prostate Cancer: A Systematic Review.

CONTEXT: Identification of early nodal recurrence after primary prostate cancer (PCa) treatment by functional imaging may guide metastasis-directed therapy such as salvage lymph node dissection (SLND). OBJECTIVE: The aim of this systematic review was to assess the oncological role and the safety of SLND in the era of modern imaging in case of exclusive nodal recurrence after primary PCa treatment with curative intent. EVIDENCE ACQUISITION: A systematic literature search in the PubMed and Cochrane databases was performed up to August 2018 according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Overall, 27 SLND series have been selected for synthesis. EVIDENCE SYNTHESIS: Prostate-specific membrane antigen or choline positron emission tomography/computed tomography was the reference detection technique. SLND was performed by open or laparoscopic approach with <10% of grade 3 or more complication rate. Mean follow-up was 29.4 mo. Complete biochemical response after SLND was achieved in 13-79.5%of cases (mean 44.3%). The 2- and 5-yr biochemical progression-free survival rates ranged from 23% to 64% and from 6% to 31%, respectively. Fiver-year overall survival was approximately 84%. Main drawbacks limiting the interpretation of the effectiveness of SLND were the retrospective design of single-center series, heterogeneity between series in terms of adjuvant treatment, endpoints, definitions of progression and study population, as well as the absence of long-term follow-up. CONCLUSIONS: A growing body of accumulated data suggests that SLND is a safe metastasis-directed therapy option in nodal recurrence after primary treatment. However, to date, high level of evidence is still missing to draw any clinically meaningful conclusion about the oncological impact of SLND on long-term endpoints. PATIENT SUMMARY: When imaging identifies exclusive nodal recurrent prostate cancer, surgery directed to the positive lesions is safe and can offer at least a temporary biochemical response. The oncological role assessed by strong clinical endpoints remains uncertain.

Are clinical guidelines designed according to guidelines? Cross-sectional assessment of quality and transparency of clinical guidelines in urology.

PURPOSE: Guidelines and recommendations become increasingly important in clinical urologic practice. This study aims to inform clinicians using guidelines on how to evaluate the quality of the methodology and transparency of these documents. METHODS: The guidelines on management of castration-resistant prostate cancer of the American Urology Association, European Association of Urology, National Comprehensive Cancer Network, National Institute for Health and Care Excellence, European Society of Medical Oncology were reviewed using the AGREE-II tool (Appraisal of Guidelines for Research and Evaluation). We reported and compared the domain scores for the domains 1 scope and purpose, 2 stakeholder involvement, 3 rigor of development, 4 clarity of presentation, 5 applicability, and 6 editorial independence (100% indicates highest-best quality score). RESULTS: The domains evaluated highest and with lowest variability were 'editorial independence' (92% {88-95%}) and 'clarity of presentation' (83% {72-90%}), while the domains with the lowest scores and most variability were 'stakeholder involvement' (56% {36-79%}) and 'applicability' (40% {30-63%}). Length and extent of detail of guidelines vary considerably, each with its own strengths and limitations and adapted to target users. Standard external review using AGREE criteria may be preferable. A formal search strategy was not performed. Findings may be outdated by guidelines' updates. CONCLUSIONS: Clinicians using practice guidelines need to be aware of the different domains of methodology and transparency used to assess the quality of guidelines contents and recommendations. Urologists increasingly use guidelines for support in evidence-based recommendations in clinical practice. It is very important to know how to assess these documents. This study applies standard criteria to compare the design and background of different available guidelines on prostate cancer no longer responding to hormonal treatment.

Effectiveness of a Combination of Cranberries, Lactobacillus rhamnosus, and Vitamin C for the Management of Recurrent Urinary Tract Infections in Women: Results of a Pilot Study.

Urinary tract infections (UTIs) are common in women and many patients with recurrent UTIs do not eradicate the condition albeit being treated with multiple courses of antibiotics. The use of nutritional supplements might reduce the risk of recurrent UTIs. However, the role of supplements taken as single agents appears to be limited. We hypothesized that a combination of cranberries, Lactobacillus rhamnosus, and vitamin C might produce a clinical benefit due to their additive or synergistic effects. We prospectively enrolled 42 consecutive women with recurrent UTIs treated with 120mg cranberries (minimum proanthocyanidin content: 32mg), 1 billion heat-killed L. rhamnosus SGL06, and 750mg vitamin C thrice daily for 20 consecutive d. Patients were advised to stop taking these supplements for 10 d and then to repeat the whole cycle three times. Patients were contacted three mo and six mo following the end of the administration of these supplements and evaluated with a semistructured interview and urinalysis. Responders were defined as the absence of symptoms and negative urinalysis or urine culture. Follow-up data were available for 36 patients. Overall, 26 (72.2%) and 22 patients (61.1%) were responders at the 3-mo and 6-month follow-up. No major side effects were recorded. The administration of cranberries, L. rhamnosus, and vitamin C might represent a safe and effective option in women with recurrent UTIs. PATIENT SUMMARY: We evaluated the effectiveness of cranberries, Lactobacillus rhamnosus, and vitamin C thrice daily for 20 consecutive d monthly for 3 mo for the management of recurrent urinary tract infections in women. Our results show that this approach might represent a safe and effective option.

Assessment of the Rate of Adherence to International Guidelines for Androgen Deprivation Therapy with External-beam Radiation Therapy: A Population-based Study.

BACKGROUND: The National Comprehensive Cancer Network and the European Association of Urology guidelines recommend using radiation therapy (RT) with androgen deprivation therapy (ADT) to treat high-risk and locally advanced prostate cancer patients. OBJECTIVE: To evaluate the degree of adherence to these guidelines. DESIGN, SETTING, AND PARTICIPANTS: Between 2003 and 2009, in the Surveillance Epidemiology and End Results (SEER)-Medicare database, 14 180 patients were diagnosed with high-risk (T1-T2 with World Health Organization histologic grade 3) or locally advanced (T3-T4 with any histologic grade) prostatic adenocarcinoma. INTERVENTION: Administration of RT-ADT versus RT alone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the rate of adherence to guidelines with respect to use of RT-ADT in the overall population and after stratification according to stage-grade groupings (T1-T2 G3 vs T3-T4 any grade), age (66-69, 70-74, 75-79, ≥80 yr), Charlson Comorbidity Index (CCI) (0, 1, ≥2), and preexisting baseline cardiovascular (CV) disease. We depicted the rate of RT-ADT administration graphically over the study period. Multivariable logistic regression analyses were performed to assess the predictors of RT-ADT use. RESULTS AND LIMITATIONS: RT-ADT rates and guideline adherence were 58-75%, with the highest rate (75%) in 2003 and the lowest (58%) in 2009. When stratified according to stage-grade groupings, age, CCI, and preexisting baseline CV disease, similar results were obtained. In multivariable analyses, year of diagnosis (p<0.001), patient age (p<0.001), stage-grade groupings (p<0.001), CCI (p=0.036), race (p<0.001), marital status (p<0.001), population density (p<0.001), and US regions (p<0.001) were independent predictors of RT-ADT use. The limitations of our study include age >65 yr and exclusive Medicare coverage. CONCLUSIONS: The rate of guideline adherence regarding the use of RT-ADT is suboptimal and decreases with time instead of increasing. PATIENT SUMMARY: This population-based study provides evidence of low adherence to international urologic guidelines regarding the combination of radiation therapy (RT) with androgen deprivation therapy (ADT) for high-risk and locally advanced prostate cancer (PCa) patients. Despite the increasing number of randomized controlled trials over time that showed a survival benefit for patients with high-risk and locally advanced PCa treated with RT-ADT compared with RT alone, the rate of adherence to guidelines decreased with time.

Morbidity and mortality after benign prostatic hyperplasia surgery: data from the American College of Surgeons national surgical quality improvement program.

BACKGROUND AND PURPOSE: With the aging population, it is becoming increasingly important to identify patients at risk for postsurgical complications who might be more suited for conservative treatment. We sought to identify predictors of morbidity after surgical treatment of benign prostatic hyperplasia (BPH) using a large national contemporary population-based cohort. METHODS: Relying on the American College of Surgeons National Surgical-Quality Improvement Program (ACS-NSQIP; 2006-2011) database, we evaluated outcomes after transurethral resection of the prostate (TURP), laser vaporization of the prostate (LVP), and laser enucleation of the prostate (LEP). Outcomes included blood-transfusion rates, length of stay, complications, reintervention rates, and perioperative mortality. Multivariable logistic-regression analysis evaluated the predictors of perioperative morbidity and mortality. RESULTS: Overall, 4794 (65.2%), 2439 (33.1%), and 126 (1.7%) patients underwent TURP, LVP, and LEP, respectively. No significant difference in overall complications (P=0.3) or perioperative mortality (P=0.5) between the three surgical groups was found. LVP was found to be associated with decreased blood transfusions (odds ratio [OR]=0.21; P=0.001), length of stay (OR=0.12; P<0.001) and reintervention rates (OR=0.63; P=0.02). LEP was found to be associated with decreased prolonged length of stay (OR=0.35; P=0.01). Men with advanced age at surgery and non-Caucasians were at increased risk of morbidity and mortality. In contrast, normal preoperative albumin and higher preoperative hematocrit (>30%) levels were the only predictors of lower overall complications and perioperative mortality. CONCLUSIONS: All three surgical modalities for BPH management were found to be safe. Advanced age and non-Caucasian race were independent predictors of adverse outcomes after BPH surgery. In patients with these attributes, conservative treatment might be a reasonable alternative. Also, preoperative hematocrit and albumin levels represent reliable predictors of adverse outcomes, suggesting that these markers should be evaluated before BPH surgery.