Nikolaos Grivas

Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy

CONTEXT Extended pelvic lymph node dissection (ePLND) is the gold standard for detecting lymph node (LN) metastases in prostate cancer (PCa). The benefit of sentinel node biopsy (SNB), which is the first draining LN as assessed by imaging of locally injected tracers, remains controversial. OBJECTIVE To assess the diagnostic accuracy of SNB in PCa. EVIDENCE ACQUISITION A systematic literature search of Medline, Embase, and the Cochrane Library (1999-2016) was undertaken using PRISMA guidelines. All studies of SNB in men with PCa using PLND as reference standard were included. The primary outcomes were the nondiagnostic rate (NDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive (FP) and false negative (FN) rates. Relevant sensitivity analyses based on SN definitions, ePLND as reference standard, and disease risk were undertaken, including a risk of bias (RoB) assessment. EVIDENCE SYNTHESIS Of 373 articles identified, 21 studies recruiting a total of 2509 patients were eligible for inclusion. Median cumulative percentage (interquartile range) results were 4.1% (1.5-10.7%) for NDR, 95.2% (81.8-100%) for sensitivity, 100% (95.0-100%) for specificity, 100% (87.0-100%) for PPV, 98.0% (94.3-100%) for NPV, 0% (0-5.0%) for the FP rate, and 4.8% (0-18.2%) for the FN rate. The findings did not change significantly on sensitivity analyses. Most studies (17/22) had low RoB for index test and reference standard domains. CONCLUSIONS SNB appears to have diagnostic accuracy comparable to ePLND, with high sensitivity, specificity, PPV and NPV, and a low FN rate. With a low FP rate (rate of detecting positive nodes outside the ePLND template), SNB may not have any additional diagnostic value over and above ePLND, although SNB appears to increase nodal yield by increasing the number of affected nodes when combined with ePLND. Thus, in high-risk disease it may be prudent to combine ePLND with SNB. PATIENT SUMMARY This literature review showed a high diagnostic accuracy for sentinel node biopsy in detecting positive lymph nodes in prostate cancer, but further studies are needed to explore the effect of sentinel node biopsy on complications and oncologic outcome.

Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer.

Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC. According to preclinical and clinical studies, combination therapies with VEGF- and checkpoint inhibitors have synergistic effect achieving improved response rates. However, toxicity in some combinations is high. In this article, we present a review of the ongoing trials with these drug combinations for RCC.

What are the Benefits and Harms of Ureteroscopy Compared with Shock-wave Lithotripsy in the Treatment of Upper Ureteral Stones? : A Systematic Review

CONTEXT Extracorporeal shock wave lithotripsy (SWL) and ureteroscopy (URS), with or without intracorporeal lithotripsy, are the most common treatments for upper ureteric stones. With advances in technology, it is unclear which treatment is most effective and/or safest. OBJECTIVE To systematically review literature reporting benefits and harms of SWL and URS in the management of upper ureteric stones. EVIDENCE ACQUISITION Databases including Medline, Embase, and the Cochrane library were searched from January 2000 to November 2014. All randomised controlled trials (RCTs), quasi-randomised controlled trials, and nonrandomised studies comparing any subtype or variation of URS and SWL were included. The primary benefit outcome was stone-free rate (SFR). The primary harm outcome was complications. Secondary outcomes included retreatment rate, need for secondary, and/or adjunctive procedures. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the quality of evidence. EVIDENCE SYNTHESIS Five thousand-three hundred and eighty abstracts and 387 full-text articles were screened. Forty-seven studies met inclusion criteria; 19 (39.6%) were RCTs. No studies on children met inclusion criteria. URS and SWL were compared in 22 studies (4 RCTs, 1 quasi-randomised controlled trial, and 17 nonrandomised studies). Meta-analyses were inappropriate due to data heterogeneity. SFR favoured URS in 9/22 studies. Retreatment rates were higher for SWL compared with URS in all studies but one. Longer hospital stay and adjunctive procedures (most commonly the insertion of a JJ stent) were more common when primary treatment was URS. Complications were reported in 11 out of 22 studies. In eight studies, it was possible to report this as a Clavien-Dindo Grade. Higher complication rates across all grades were reported for URS compared with SWL. For intragroup (intra-SWL and intra-URS) comparative studies, 25 met the inclusion criteria. These studies varied greatly in outcomes measured with data being heterogeneous. CONCLUSIONS Compared with SWL, URS was associated with a significantly greater SFR up to 4 wk but the difference was not significant at 3 mo in the included studies. URS was associated with fewer retreatments and need for secondary procedures, but with a higher need for adjunctive procedures, greater complication rates, and longer hospital stay. PATIENT SUMMARY In this paper, the relative benefits and harms of the two most commonly offered treatment options for urinary stones located in the upper ureter were reviewed. We found that both treatments are safe and effective options that should be offered based on individual patient circumstances and preferences.

The Efficacy of Medical Expulsive Therapy (MET) in Improving Stone-free Rate and Stone Expulsion Time, After Extracorporeal Shock Wave Lithotripsy (SWL) for Upper Urinary Stones: A Systematic Review and Meta-analysis

In this meta-analysis, we included randomized studies on medical expulsive therapy implemented following shock wave lithotripsy for renal and ureteral stones. Pooled results demonstrated the efficacy of α-blockers, nifedipine, Rowatinex, and Uriston in increasing stone clearance. In addition, the time to stone elimination, the intensity of pain, the formation of steinstrasse, and the need for auxiliary procedures were reduced mainly with α-blockers. Expulsion rate was not correlated with the type of α-blocker, the diameter, and the location of stone. Our results show that medical expulsive therapy for residual fragments after shock wave lithotripsy should be implemented in clinical practice.

Quantitative assessment of fascia preservation improves the prediction of membranous urethral length and inner levator distance on continence outcome after robot-assisted radical prostatectomy

To determine whether preoperative prostate/pelvic anatomical structures and intraoperative fascia preservation (FP) predict continence recovery after robot‐assisted radical prostatectomy (RARP).

The Impact of Adding Sentinel Node Biopsy to Extended Pelvic Lymph Node Dissection on Biochemical Recurrence in Prostate Cancer Patients Treated with Robot-Assisted Radical Prostatectomy

The benefit of adding sentinel node biopsy (SNB) to extended pelvic lymph node dissection (ePLND) remains controversial. The aim of our study was to evaluate biochemical recurrence (BCR) after robot-assisted radical prostatectomy and ePLND in prostate cancer patients, stratified by the application of SNB. The results were compared with the predictions of the updated Memorial Sloan Kettering Cancer Center nomogram. Methods: Between January 2006 and November 2016, 920 patients underwent robot-assisted radical prostatectomy and ePLND with or without SNB (184 and 736 patients, respectively). BCR was defined as 2 consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan–Meier method and Cox regression analyses were used to identify predictors of BCR. Results: Median follow-up was 28 mo (interquartile range, 13–56.7 mo). The 5-y BCR-free survival rate was 80.5% and 69.9% in the ePLND+SNB and ePLND groups, respectively. At multivariate analysis, prostate-specific antigen level, primary Gleason grade greater than 3, seminal vesicle invasion, and higher number of removed and positive nodes were independent predictors of BCR in the ePLND group. In the ePLND+SNB group, only the number of positive nodes was an independent predictor of BCR. The overall accuracy of the Memorial Sloan Kettering Cancer Center nomogram was higher in the ePLND+SNB than in the ePLND group. However, the nomogram was underestimating the probability of BCR-free status in the ePLND+SNB group, whereas the ePLND group was performing as predicted. Conclusion: Adding SNB to ePLND improves BCR-free survival, although the precise explanation of this observation remains speculative. Our results should be interpreted cautiously, given the nonrandomized nature and the selection bias of the study.

Patterns of Benign Prostate Hyperplasia Based on Magnetic Resonance Imaging Are Correlated With Lower Urinary Tract Symptoms and Continence in Men Undergoing a Robot-assisted Radical Prostatectomy for Prostate Cancer

OBJECTIVE To investigate the association between benign prostatic hyperplasia (BPH) patterns, classified by magnetic resonance imaging (MRI), with lower urinary tract symptoms (LUTS) or continence, preoperatively and after robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS This retrospective study included 49 prostate cancer patients, with prostate size >47 cm3, who underwent an endorectal MRI followed by RARP. Five BPH patterns were identified according to Wasserman, and additional prostate measurements were recorded. LUTS were assessed using the International Prostate Symptom Score and the PR25-LUTS-Questionnaire score. Continence was assessed using the International Consultation of Incontinence Questionnaire-Short Form. RESULTS BPH pattern 3 (44.9%) was identified most common, followed by pattern 5 (26.6%), 1 (24.5%), and 2 and 4 (both 2%). BPH patterns were significant predictors of preoperative LUTS, with pedunculated with bilateral transition zone (TZ) and retrourethral enlargement (pattern 5) causing more severe symptoms compared with bilateral TZ and retrourethral enlargement (pattern 3) and bilateral TZ enlargement (pattern 1), whereas pattern 3 was additionally associated with more voiding symptoms compared with pattern 1. None of the BPH patterns was predictive of postoperative LUTS and continence. Independent predictors of continence at 12 months were lower preoperative PR25-LUTS score (P = .022) and longer membranous urethral length (P = .025). CONCLUSION MRI is useful for classifying patients in BPH patterns which are strongly associated with preoperative LUTS. However, BPH patterns did not predict remnant LUTS or postoperative incontinence. Postoperative continence status was only associated with preoperative LUTS and membranous urethra length.

Ultrasensitive prostate-specific antigen level as a predictor of biochemical progression after robot-assisted radical prostatectomy: Towards risk adapted follow-up

Ultrasensitive prostate‐specific antigen (USPSA) is useful for stratifying patients according to their USPSA‐based risk. Aim of our study was to determine the usefulness of USPSA as predictor of biochemical recurrence (BCR) after robot‐assisted radical prostatectomy (RARP).

Long-term Survival After Resection of Sentinel Node Metastatic Renal Cell Carcinoma

We present a case of a patient who took part in a prospective sentinel lymph node (SN) study to investigate the drainage pattern from renal tumors. The patient was treated with laparoscopic radical nephrectomy, for a clinically node negative left renal tumor of 6 cm combined with SN and non-SN lymph node dissection. Histopathologic examination revealed a papillary type 2 pT1b renal cell carcinoma with 2 para-aortic metastatic SNs. No adjuvant treatment was applied. The patient is free of disease at 63 months after surgery.

Lymphatic Drainage from Renal Tumors In Vivo: A Prospective Sentinel Node Study Using SPECT/CT Imaging

Purpose: Lymphatic drainage from renal tumors is unpredictable. In vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern of renal tumors in vivo with single photon emission/computerized tomography after intratumor radiotracer injection. Materials and Methods: We performed a phase II, prospective, single arm study to investigate the distribution of sentinel nodes from renal tumors on single photon emission/computerized tomography. Patients with cT1‐3 (less than 10 cm) cN0M0 renal tumors of any subtype were enrolled in analysis. After intratumor ultrasound guided injection of 0.4 ml 99mTc‐nanocolloid we performed preoperative imaging of sentinel nodes with lymphoscintigraphy and single photon emission/computerized tomography. Sentinel and locoregional nonsentinel nodes were resected with a &ggr; probe combined with a mobile &ggr; camera. The primary study end point was the location of sentinel nodes outside the locoregional retroperitoneal templates on single photon emission/computerized tomography. Using a Simon minimax 2‐stage design to detect a 25% extralocoregional retroperitoneal template location of sentinel nodes on imaging at &agr; = 0.05 and 80% power at least 40 patients with sentinel node imaging on single photon emission/computerized tomography were needed. Results: Of the 68 patients 40 underwent preoperative single photon emission/computerized tomography of sentinel nodes and were included in primary end point analysis. Lymphatic drainage outside the locoregional retroperitoneal templates was observed in 14 patients (35%). Eight patients (20%) had supradiaphragmatic sentinel nodes. Conclusions: Sentinel nodes from renal tumors were mainly located in the respective locoregional retroperitoneal templates. Simultaneous sentinel nodes were located outside the suggested lymph node dissection templates, including supradiaphragmatic sentinel nodes in more than a third of the patients.