Can the Leukocyte Esterase Strip Test Predict Persistence of Periprosthetic Joint Infection at Second-Stage Reimplantation?

BACKGROUND: We evaluated the reliability of intraoperative assessment of leukocyte esterase (LE) in synovial fluid samples from patients undergoing reimplantation following implant removal and spacer insertion for periprosthetic joint infection (PJI). Our hypothesis was that a positive intraoperative LE test would be a better predictor of persistent infection than either serum C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) or the combination of serum CRP and ESR. METHODS: The records of 76 patients who received a 2-stage exchange for PJI were retrospectively reviewed. Synovial fluid was collected for LE measurement during surgery before arthrotomy in 79 procedures. Receiver operating characteristic curves were generated. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) of LE, CRP, ESR, and CRP + ESR were calculated. RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value of the LE assay were 82%, 99%, 90%, and 97%, respectively. Receiver operating characteristic analysis revealed an LE threshold of 1.5 between the first (negative) and the second (positive) level of the ordinal variable, so that a grade starting from 1+ was accurate for a diagnosis of persistent infection (AUC 0.9044). The best thresholds for the CRP and the ESR assay were 8.25 mg/L (82% sensitivity, 84% specificity, AUC 0.8416) and 45 mm/h (55% sensitivity, 87% specificity, AUC 0.7493), respectively. CONCLUSION: The LE strip test proved a reliable tool to diagnose persistence of infection and outperformed the serum CRP and ESR assays. The strip test provides a valuable intraoperative diagnostic during second-stage revision for PJI.

Underestimation of Positron Emission Tomography/Computerized Tomography in Assessing Tumor Burden in Prostate Cancer Nodal Recurrence: Head-to-Head Comparison of 68Ga-PSMA and 11C-Choline in a Large, Multi-Institutional Series of Extended Salvage Lymph Node Dissections.

PURPOSE: We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer. MATERIALS AND METHODS: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using 11C-choline (407, 63%) or 68Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer (11C-choline vs 68Ga-PSMA) and tumor burden underestimation. RESULTS: Overall the extent of tumor burden underestimation was significantly higher in the 11C-choline group compared to the 68Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with 68Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2). CONCLUSIONS: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. 68Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from 68Ga-PSMA over 11C-choline in assessing the extent of nodal recurrence.

Correction to: Metastasectomy for visceral and skeletal oligorecurrent prostate cancer.

The authors have requested the removal of the Excel file in Electronic Supplementary Material to protect patient's privacy.

Metastasectomy for visceral and skeletal oligorecurrent prostate cancer.

OBJECTIVES: Metastasis direct therapy (MDT) is a common practice in different fields of oncology. However, there is a lack of data on surgical MDT in visceral/skeletal oligometastatic prostate cancer (PCa). We aimed to assess the role of surgical excision of visceral and skeletal PCa recurrence. METHODS: Seventeen PCa patients experienced metachronous visceral or skeletal oligometastatic recurrence following maximal local treatment. Oligometastatic recurrence was defined as 1-3 lesions, detected with the best imaging technique available at the time of diagnosis. All patients underwent metastasectomy and were followed for a median of 43 months. Postoperative complications were graded using the Clavien-Dindo classification of surgical complications. Kaplan-Meier plots were used to assess overall survival. RESULTS: Fourteen patients (82%) had visceral lesions, two had bone lesions (12%), and one had an abdominal wall metastasis (6%). Four patients (24%) were under active ADT at the time of metastasectomy. PSA decreased after metastasectomy in 16 (94%) patients. Ten (77%) of the 13 ADT-naïve patients had a PSA decrease of ≥ 50%. Following metastasectomy, 16 (94.1%) patients developed metastatic recurrence of which 11 (64.7%) were again oligometastatic, amenable for repeated MDT. The median time to metastatic recurrence was 14 months (range 6.4-40). We observed 8% Clavien-Dindo grade 3-4 complications in 21 procedures. CONCLUSIONS: In this report, we analyzed the outcomes of surgical excision of visceral and skeletal PCa recurrence following primary treatment. We found that removing metastasis to the bone and viscera can be associated with long-term disease-free periods at a low rate of serious complications. These exploratory results should be confirmed in prospective studies.

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel-Lindau patients.

CONTEXT: Von Hippel-Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death. OBJECTIVE: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients. MATERIALS AND METHODS: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers. RESULTS: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC. DISCUSSION AND CONCLUSION: A1AT and APOH could be promising non-invasive biomarkers.

Bone morphology and morphometry of the lateral femoral condyle is a risk factor for ACL injury.

PURPOSE: The purpose of this study was to investigate the influence of the knee lateral compartment bony morphology and morphometry on risk of sustaining an anterior cruciate ligament (ACL) injury. METHODS: A total of 400 age and sex-matched patients (200 ACL-ruptured and 200 ACL-intact) were included. The lateral femoral and tibial bone morphology and morphometric parameters were measured on knee lateral radiographs, taken at 30° of knee flexion with overlapping of the femoral condyles. Radiographic measurements included: anteroposterior-flattened surface of the femur's lateral condyle (XY); femur's diaphysis anteroposterior distance (A); anteroposterior distance of the femur's lateral condyle (B); height of the femur's lateral condyle (C); anteroposterior distance of the tibial plateaus (AB); tibial slope. In addition, three morphological ratios were calculated: B/AB; B/XY; XY/AB (Porto ratio). RESULTS: Most of bone morphological parameters were different between genders (P < 0.05). ACL-ruptured female subjects showed statistical significant smaller condyle heights (C), smaller distances of the flattened surface of the distal femoral condyle (XY), smaller tibial plateau anteroposterior distances (AB), and higher XY/AB ratio (P < 0.05). ACL-ruptured male subjects had statistical significant smaller condyle height (C), anteroposterior distance of the femur's lateral condyle (B), tibial plateau anteroposterior distances (AB), and tibial slope (P < 0.05). Multivariate logistic regression model showed that five morphological parameters (A, XW, XY, XZ, and AB) were significantly associated with ACL rupture (AUC = 0.967, P < 0.001). Calculated ratios (XY/AB; B/AB; B/XY) showed a significant accuracy in identifying individuals with ACL injury (P < 0.001). CONCLUSIONS: The most important finding of this study was that the calculated ratios (XY/AB; B/AB; B/XY) showed a significant accuracy in identifying the individuals with and without an ACL injury. Within this line, a longer flat surface of the lateral femoral condyle or higher Porto ratio (XY/AB) is associated with a lower the risk of ACL injury. Moreover, when considering the combination of five primary bone morphology and morphometric parameters (A, XW, XY, XZ, and AB), the accuracy in identifying these individuals was excellent (AUC = 0.967). These findings may contribute to injury risk assessment, sports participation, and injury prevention counseling and surgical planning refining by identifying high-risk patients who would benefit from the addition of associated procedures to the anatomic ACL reconstruction aiming the improvement of knee stability and decrease the risk of further injuries. LEVEL OF EVIDENCE: III, case-control study.

Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation.

BACKGROUND: Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105(+) CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105(-) TCs) and their EVs. METHODS: Maturation of monocyte-derived DCs was studied in presence of CD105(+) CSCs and CD105(-) TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors. RESULTS: The results obtained demonstrate that both CD105(+) CSCs and CD105(-) TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105(+) CSCs was significantly greater than that of CD105(-) TCs. EVs derived from CD105(+) CSCs and in less extent, those derived from CD105(-) TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation. CONCLUSIONS: In conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.

Ultrasound-Guided Hip Injections with High Density Hyaluronic Acid: Outcome at One Year Follow Up.

Background: The ultrasound-guided viscosupplementation of the hip joint with hyaluronic acid (HA) is considered a standard procedure among the conservative treatments for hip arthritis. The aim of this study was to evaluate the clinical benefit and the incidence of adverse events of the technique in an observational study at one year follow up. Methods: We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis who underwent intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score (mHHS), WOMAC (Western Ontario and McMaster University), and Hip Outcome Score (HOS) with subscale Sport (HOSs), for pain the Visual Analogic Scale (VAS). The patients were classified according to Tonnis' radiological classification of arthritis (range 0-3): 20 patients (grade 0), 32 (grade 1), 18 (grade 2), 15 (grade 3). Results: At last follow up, all the scales increased: mHHS from 59.35 to 82.1, HOS from 69.45 to 78.53, HOss from 47.4 to 58.11, VAS from 6.09 to 3.97, WOMAC from 33.2 to 31.5 (p < 0.05 for all the parameters); the results were elaborated with GraphPad Prism v5.0 (Prism Software La Jolla, CA, USA) using Wilcoxon's test. A total of 13 patients out of 85 needed arthroplasty, all classified as Tonnis grade 3. No serious adverse events were noted due to the procedure. Conclusions: Based on our findings, indication for the use of hyaluronic acid is limited to patients with mild to moderate arthritis. Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term.

Metal Hypersensitivity or Missed Periprosthetic Joint Infection? A Critical Review.

The World Association Against Infection in Orthopedics And Trauma (W.A.I.O.T.) Study Group on Bone And Joint Infection Definitions Metal hypersensitivity (MHS) has been investigated by several authors as a possible reason for painful total joint arthroplasty, with controversial results. Periprosthetic joint infection (PJI) is another possible source of unexplained pain and implant failure that may be difficult to diagnose if not properly investigated. We performed this critical review to assess whether the current literature on MHS includes an adequate diagnostic workup to discern metal allergy from PJI. The results of this review highlight the importance of assessing patients for PJI before making a diagnosis of MHS and emphasize that the methods currently used to exclude PJI are substantially inadequate. Therefore, well-designed clinical trials with adequate diagnostic protocols and definitions of PJI that can differentiate MHS from low-grade PJI are needed. [Orthopedics. 2022;45(2):e73-e78.].

Defining the Most Informative Intermediate Clinical Endpoints for Patients Treated with Salvage Radiotherapy for Prostate-specific Antigen Rise After Radical Prostatectomy.

Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell's c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0-8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44-11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. PATIENT SUMMARY: Clinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials.

Oncological outcomes of salvage radical prostatectomy for recurrent prostate cancer in the contemporary era: A multicenter retrospective study.

BACKGROUND: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.

Prostate-Specific Antigen Modulatory Effect of a Fermented Soy Supplement for Patients with an Elevated Risk of Prostate Cancer: a Non-Randomized, Retrospective Observational Registration.

OBJECTIVE: To investigate the efficacy of a 6-month fermented soy supplement (equol-containing), measured by prostate-specific antigen (PSA) stabilization or PSA decrease from baseline (PSA modulatory effect) in men with an elevated risk of prostate cancer (PCa), with a WHO performance 0-2 and a follow-up of 12 months. METHODS: The patient population consisted of men with an elevated risk of PCa and a prior negative prostate biopsy within 1 year from starting therapy. Serum PSA values were recorded at inclusion (iPSA), at 6 months (1PSA), and optionally at 12 months (2PSA). Statistical analysis was carried out using the Wilcoxon rank sum test (p < 0.05). RESULTS: In total, 137 men used fermented soy for any prostatic reason. After inclusion criteria for an elevated risk of PCa and a prior negative prostate biopsy, we selected 58 patients. Among these, there was a significant PSA modulatory effect (iPSA-1PSA, p = 0.003). This modulatory effect was more strongly evident in the subgroup of patients with an elevated iPSA (≥ 4 ng/ml) (n = 33, iPSA-1PSA, p = 0.003, iPSA-2PSA, p = 0.002). CONCLUSIONS: We demonstrated a significant PSA modulatory effect of a 6-month fermented soy supplement in men with an elevated risk of PCa and a prior negative prostate biopsy. This positive effect is currently being investigated in a prospective study. Further evaluation of the role of fermented soy supplements is warranted in a preventive and therapeutic setting of men at an elevated risk of PCa.

Novel Insights into the Management of Oligometastatic Prostate Cancer: A Comprehensive Review.

CONTEXT: The current standard of care for metastatic prostate cancer (PCa) is androgen deprivation therapy (ADT) plus either docetaxel or abiraterone. Growing evidence suggests that metastasis-directed therapy (MDT) and/or local therapy targeted to the primary tumour (ie, prostate) may be of benefit in the setting of oligometastatic disease. Several prospective studies are underway; however, until robust evidence is available to guide treatment decisions, physicians are challenged with how best to manage patients with oligometastases. OBJECTIVE: This comprehensive review aims to collate the available evidence to date for a role of MDT and/or prostate-targeted therapy in the setting of oligometastatic PCa, as well as discuss ongoing trials in this setting. EVIDENCE ACQUISITION: We searched PubMed for the combination of "prostate cancer" and "oligometastatic", "oligometastases", "oligometastasis", "solitary metastases", "stereotactic body radiotherapy", "SBRT", "stereotactic ablative radiotherapy", "SABR", "salvage lymphadenectomy", or "metastasectomy" in publications over the last 20yr. We also searched ClinicalTrials.gov to identify relevant ongoing trials. EVIDENCE SYNTHESIS: The studies were divided according to the timing of metastasis into synchronous (ie, detected at the time of primary PCa diagnosis) and metachronous (ie, detected after treatment of the primary tumour), and according to treatment modality into MDT (including salvage lymph node dissection [sLND]) and prostate-targeted treatment. For MDT of synchronous/metachronous metastases, we included 16 completed studies and 11 ongoing prospective studies. In the case of sLND for nodal-only recurrence after primary treatment with curative intent, we included 11 completed studies. Finally, for prostate-targeted treatment of synchronous metastatic PCa, we included 25 completed studies and 11 ongoing prospective studies. In selected patients with oligorecurrent disease, early detection and aggressive treatment of metastatic lesions (surgery or radiotherapy) appears to be a feasible strategy and may delay the use of systemic therapies. MDT is a promising option in oligometastatic PCa patients, but more robust data are needed. In the setting of synchronous oligometastatic disease, aggressive cytoreductive treatment needs further data to confirm the benefits. CONCLUSIONS: In this review, we provide a comprehensive overview of the current literature on the treatment of patients with oligometastatic PCa. The data suggest that although ADT plus either docetaxel or abiraterone remains the mainstay of treatment for mPCa, in oligometastatic PCa, improved outcomes may be achieved with metastasis- and prostate-targeted therapies. The studies included in this review are mainly retrospective in nature, limiting the strength of the evidence they provide. Prospective studies are ongoing, and their results are eagerly awaited. PATIENT SUMMARY: We reviewed the treatment of patients with prostate cancer that has spread to five sites or fewer. We conclude that while androgen deprivation plus either docetaxel or abiraterone should remain the standard of care, there is evidence that treatment targeted at the metastases and the primary tumour may improve the outcome for the patient and potentially delay the use of systemic treatment.

Which Patients with Clinically Node-positive Prostate Cancer Should Be Considered for Radical Prostatectomy as Part of Multimodal Treatment? The Impact of Nodal Burden on Long-term Outcomes.

BACKGROUND: A role for local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies has been proposed. However, no data are available to identify men who would benefit from RP in this setting. OBJECTIVE: To identify predictors of clinical recurrence (CR) in surgically managed PCa patients with clinical lymphadenopathies. DESIGN, SETTING, AND PARTICIPANTS: We identified 162 patients with lymphadenopathies treated with RP and lymph node dissection at three referral centers. OUTCOME MEASURES AND STATISTICAL ANALYSES: CR was defined as the onset of metastases detected by conventional imaging. Kaplan-Maier analyses assessed time to CR after stratifying patients according to the site of lymphadenopathies and nodal burden. Regression tree analysis stratified patients into risk groups on the basis of their preoperative characteristics. RESULTS AND LIMITATIONS: Overall, 80% of patients had lymphadenopathies in the pelvis alone and 20% in the retroperitoneum±pelvis. The median size of positive nodes was 13mm. A total of 84 patients (52%) received neoadjuvant androgen deprivation therapy and 127 (78%) had pathological lymph node invasion. The median follow-up for survivors was 64 mo. The 8-yr CR-free and CSM-free survival rates were 59% and 80%, respectively. Biopsy grade group and preoperative nodal burden should identify patients more likely to experience CR. While <10% of men with biopsy grade group 1-3 and two or fewer clinical lymphadenopathies developed CR, up to 60% of patients with biopsy grade group 4-5 and retroperitoneal node involvement ultimately experienced CR at 8 yr after RP. The discrimination of the regression tree was 76% according to the area under the receiver operating characteristic curve. Our study is limited by potential unmeasured confounders and the relatively small sample size. CONCLUSIONS: Surgery in a multimodal setting might play a role in PCa patients with biopsy grade group 1-3 and/or enlarged nodes in the pelvis. Conversely, grade group 4-5 PCa and lymphadenopathies in the retroperitoneum are associated with worse oncologic outcomes. PATIENT SUMMARY: Approximately half of prostate cancer patients with clinical lymphadenopathies treated with radical prostatectomy are free from metastases at 8-yr follow-up. Radical prostatectomy with or without systemic therapies might play a role in selected patients with biopsy grade group 1-3 disease and/or enlarged nodes in the pelvis. Conversely, a higher grade group and the presence of lymphadenopathies in the retroperitoneum should identify candidates for systemic therapies upfront.

Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer: Results from a Large, Multi-institutional Analysis.

BACKGROUND: Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients. OBJECTIVE: To identify the optimal candidates for SLND based on preoperative characteristics. DESIGN, SETTING, AND PARTICIPANTS: The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand. INTERVENTION: SLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model. RESULTS AND LIMITATIONS: Median follow-up was 30 (interquartile range, 16-50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel'sC index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the "treat-all" option at all the threshold probabilities. CONCLUSIONS: We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach. PATIENT SUMMARY: The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery.

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study.

BACKGROUND: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. OBJECTIVE: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. DESIGN, SETTING, AND PARTICIPANTS: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). RESULTS AND LIMITATIONS: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. CONCLUSIONS: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. PATIENT SUMMARY: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT.

Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy: Long-term Results from a Large, Multi-institutional Series.

BACKGROUND: Hormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels. OBJECTIVE: To test if the impact of androgen deprivation therapy (ADT) on metastasis in patients undergoing early SRT varies according to prostate cancer (PCa) features. DESIGN, SETTING, AND PARTICIPANTS: A total of 525 patients received SRT at PSA levels ≤2ng/ml. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Multivariable Cox regression analyses assessed factors associated with metastasis. We tested the hypothesis that the impact of ADT varied according to the risk of metastasis. An interaction with groups (concomitant ADT vs no ADT) and the probability of distant metastasis according to a newly developed model was tested. A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT. RESULTS AND LIMITATIONS: Median PSA and radiotherapy dose were 0.42ng/ml and 66Gy, respectively. Overall, 178 (34%) patients received ADT. At a median follow-up of 104 mo, 71 patients experienced metastasis. Grade group ≥4 (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.01-3.30), pT3b/4 (HR: 2.61; 95% CI: 1.51-4.52), and dose (HR: 0.82; 95% CI: 0.76-0.89) were associated with metastasis. The impact of ADT differed according to the risk of metastasis calculated using a multivariable model (p=0.01). This was confirmed when considering patients treated with early SRT (p=0.046), where ADT was associated with a reduction in the rate of metastasis only in eSRT; patients with more aggressive characteristics (ie, pT3b/4 and grade group ≥4, or pT3b/4 and PSA at eSRT ≥0.4ng/ml). CONCLUSIONS: The beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics, such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP. PATIENT SUMMARY: The oncological benefits of concomitant androgen deprivation therapy (ADT) in patients undergoing salvage radiotherapy (SRT) vary according to pathological characteristics. Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT. Conversely, the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features.

Urology Residency Training in Italy: Results of the First National Survey.

BACKGROUND: Numerous surveys have been performed to determine the competence and the confidence of residents. However, there is no data available on the condition of Italian residents in urology. OBJECTIVE: To investigate the status of training among Italian residents in urology regarding scientific activity and surgical exposure. DESIGN, SETTING, AND PARTICIPANTS: A web-based survey that included 445 residents from all of the 25 Italian Residency Programmes was conducted between September 2015 and November 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcomes were represented by scientific activity, involvement in surgical procedures, and overall satisfaction. RESULTS AND LIMITATIONS: In total, 324 out of 445 (72.8%) residents completed the survey. Overall, 104 (32%) residents had not published any scientific manuscripts, 148 (46%) published ≤5, 38 (12%) ≤10, 26 (8%) ≤15, four (1%) ≤20, and four (1%) >20 manuscripts, respectively. We did not observe any differences when residents were stratified by sex (p=0.5). Stent positioning (45.7%), extracorporeal shock wave lithotripsy (30.9%), transurethral resection of bladder tumor (33.0%), hydrocelectomy (24.7%), varicocelectomy (17%), ureterolithotripsy (14.5%), and orchiectomy (12.3%) were the surgical procedures more frequently performed by residents. Overall, 272 residents (84%) expressed a good satisfaction for urology specialty, while 178 (54.9%) expressed a good satisfaction for their own residency programme. We observed a statistically decreased trend for good satisfaction for urology specialty according to the postgraduate year (p=0.02). CONCLUSIONS: Italian Urology Residency Programmes feature some heavy limitations regarding scientific activity and surgical exposure. Nonetheless, satisfaction rate for urology specialty remains high. Further improvements in Residency Programmes should be made in order to align our schools to others that are actually more challenging. PATIENT SUMMARY: In this web-based survey, Italian residents in urology showed limited scientific productivity and low involvement in surgical procedures. Satisfaction for urology specialty remains high, demonstrating continuous interest in this field of study from residents.

Impact of Early Salvage Radiation Therapy in Patients with Persistently Elevated or Rising Prostate-specific Antigen After Radical Prostatectomy.

BACKGROUND: Salvage radiation therapy (SRT) is a recommended treatment option for biochemical recurrence after radical prostatectomy (RP). However, its effectiveness may be limited to specific categories of patients. OBJECTIVE: We aimed to identify the optimal candidates for early SRT after RP. DESIGN, SETTING, AND PARTICIPANTS: The study included 925 node-negative patients treated with SRT after RP at seven institutions. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP that was defined as PSA level ≥0.1 ng/ml at 1 mo after surgery. All patients received local radiation to the prostate and seminal vesicle bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome measured was distant metastasis after SRT. Regression tree analysis was used to develop a risk-stratification tool. Multivariable Cox regression analysis and nonparametric curve fitting methods were used to explore the relationship between PSA level at SRT and the probability of metastasis-free survival at 8 yr. RESULTS AND LIMITATIONS: At a median follow-up of 8.0 yr, 130 patients developed distant metastasis. At multivariable analysis, pre-SRT PSA level was significantly associated with distant metastasis (hazard ratio: 1.06, p<0.0001). However, when patients were stratified into five risk groups using regression tree analysis (area under the curve: 85%), early SRT administration provided better metastasis-free survival in three groups only: (1) low risk: undetectable PSA after RP, Gleason score ≤7, and tumour stage ≥pT3b, (2) intermediate risk: undetectable PSA after RP with Gleason score ≥8, (3) high risk: PSA persistence after RP with Gleason score ≤7. CONCLUSIONS: We developed an accurate risk stratification tool to facilitate the individualised recommendation for early SRT based on prostate cancer characteristics. Early SRT proved to be beneficial only in selected groups of patients who are more likely to be affected by clinically significant but not yet systemic recurrence at the time of salvage treatment administration. PATIENT SUMMARY: In patients affected by prostate cancer recurrence after radical prostatectomy, the early administration of salvage radiation therapy is beneficial only for selected subgroups of patients. In this study, these groups of patients were identified.