Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

INTRODUCTION: Lymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. METHODS: Retrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). RESULTS: A total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN - group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN - patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). CONCLUSION: Conventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.

Is Unilateral Lymphadenectomy an Option in Selected Patients with Prostate Cancer?

Background: Evidence regarding the relationship between the laterality of lymph node invasion (LNI) and the prostatic lobe affected is limited. Our aim was to review our records of patients with exclusively unilateral localised prostate cancer (PCa) with metastatic LN involvement. Methods: Between 2006 and 2023, after radical prostatectomy and extended pelvic lymphadenectomy at our centre, thirty patients with intermediate-high risk unilateral PCa and pN1 disease were identified. To perform a retrospective study, data were obtained from a prospective collected database approved by the ethical committee at the Valencian Oncology Institute Foundation. Descriptive and comparative statistical analysis was made using software R. The Fisher’s Exact test was employed to analyse the categorical variables. In terms of continuous variables, both tumour volume and number of nodes retrieved exhibited normality; Hence Student’s T-test was employed. Mann-Whitney U test was utilized for the number of positive nodes. Results: The median age and prostate specific antigen (PSA) at diagnosis were 66 years old (interquartile range (IQR): 63.3–70.9) and 14.6 ng/mL (IQR: 7.4–21.5), respectively. Median follow-up time was 67 months (IQR: 35.9–92.9). Nineteen patients (63%) had a Gleason score of 7, and the rest had a Gleason score of 8–10. Most patients (73%) had locally advanced disease. Baseline characteristics were comparable between groups (p-value > 0.05). Twenty-two patients (73%) had concordance between the laterality of the PCa lesion and the LNI. All the patients with right prostatic cancer had exclusive ipsilateral LNI. Conclusions: In our experience, the majority of patients with unilateral PCa had exclusively ipsilateral LNI. However, sparing contralateral LN dissection in unilateral PCa should not be an option... (AU)

A Phase 2 Randomized Open-label Study of Oral Darolutamide Monotherapy Versus Androgen Deprivation Therapy in Men with Hormone-sensitive Prostate Cancer (EORTC-GUCG 1532).

BACKGROUND AND OBJECTIVE: Darolutamide is an androgen receptor inhibitor that increases overall survival in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer (PCa). This phase 2 study assessed the efficacy and safety of darolutamide as monotherapy without ADT in patients with eugonadal testosterone levels. METHODS: This was a 24-wk, open-label, randomized study of patients with hormone-sensitive, histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH); an Eastern Cooperative Oncology Group performance status score of 0/1; and life expectancy >1 yr. All patients received darolutamide 600 mg bid or a commercially available GnRH analog. The primary endpoint is a prostate-specific antigen (PSA) response, defined as a ≥80% decline at week 24 relative to baseline in the darolutamide study arm. The GnRH arm is used as an internal control. The secondary endpoints included changes in T levels, safety/tolerability, and quality of life. KEY FINDINGS AND LIMITATIONS: Among 61 men enrolled, the median (range) age was 72 yr (53-86 yr); 42.6% of them had metastases. In the darolutamide arm, the evaluable population with available PSA values at baseline and week 24 consisted of 23 patients. Twenty-three (100%) evaluable darolutamide patients achieved a PSA decline of >80% at week 24 (primary endpoint), with a median (range) decrease of -99.1% (-91.9%, -100%). Serum T levels increased by a median (range) of 44.3 (5.7-144.0) at week 24, compared with baseline. In the darolutamide arm, 48.4% of men reported drug-related adverse events (AEs; mostly grade 1 or 2). The most frequent treatment-emergent AEs included gynecomastia (35.5%), fatigue (12.9%), hot flush (12.9%), and hypertension (12.9%). Health-related quality of life measures are descriptive, and GnRH arm results will be presented as an internal reference. CONCLUSIONS AND CLINICAL IMPLICATIONS: Darolutamide monotherapy was associated with a significant PSA response in nearly all men with hormone-naïve PCa. Testosterone-level changes and most common AEs (gynecomastia, fatigue, hypertension, and hot flush) were consistent with potent androgen receptor inhibition. PATIENT SUMMARY: In this study, we report the first use of darolutamide, a novel antiandrogen, as monotherapy without androgen deprivation therapy (ADT). The study shows that darolutamide induce a profound suppression of prostate-specific antigen in all patients, with a safety profile different from that of ADT.

Sentinel Lymph Node Biopsy in Prostate Cancer: An Overview of Diagnostic Performance, Oncological Outcomes, Safety, and Feasibility.

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

Personalised indocyanine-guided lymphadenectomy for prostate cancer: a randomised clinical trial.

OBJECTIVES: To study the safety and efficacy of a personalised indocyanine-guided pelvic lymph node dissection (PLND) against extended PLND (ePLND) during radical prostatectomy (RP). PATIENTS AND METHODS: Patients who were candidates for RP and lymphadenectomy, with intermediate- or high-risk prostate cancer (PCa) according to the National Comprehensive Cancer Network guidelines, were enrolled in this randomised clinical trial. Randomisation was made 1:1 to indocyanine green (ICG)-PLND (only ICG-stained LNs) or ePLND (obturator fossa, external, internal, and common iliac and presacral LNs). The primary endpoint was the complication rate within 3 months after RP. Secondary endpoints included: rate of major complications (Clavien-Dindo Grade III-IV), time to drainage removal, length of stay, percentage of patients classified as pN1, number of LNs removed, number of metastatic LNs, rate of patients with undetectable prostate-specific antigen (PSA), biochemical recurrence (BCR)-free survival, and rate of patients with androgen-deprivation therapy at 24 months. RESULTS: A total of 108 patients were included with a median follow-up of 16 months. In all, 54 were randomised to ICG-PLND and 54 to ePLND. The postoperative complication rate was higher in the ePLND (70%) vs the ICG-PLND group (32%) (P < 0.001). Differences between major complications in both groups were not statically significant (P = 0.7). The pN1 detection rate was higher in the ICG-PLND group (28%) vs the ePLND group (22%); however, this difference was not statistically significant (P = 0.7). The rate of undetectable PSA at 12 months was 83% in the ICG-PLND vs 76% in the ePLND group, which was not statistically significant. Additionally, there were no statistically significant differences in BCR-free survival between groups at the end of the analysis. CONCLUSIONS: Personalised ICG-guided PLND is a promising technique to stage patients with intermediate- and high-risk PCa properly. It has shown a lower complication rate than ePLND with similar oncological outcomes at short-term follow-up.

A shared origin from a common ancestor: A case report of two histologically different tumors.

The origin of tumors has been under discussion over the years. Different theories have been suggested to explain this phenomenon. Among them, the Cancer-Stem Cells model, is one of the most outstanding. In this study, we reported a case of a 72-year-old man who presented two histologically different tumors with a 7-years gap, a Penile Squamous Cell Carcinoma and a Pleomorphic Undifferentiated Sarcoma, that share some molecular features. Phonotypical differences were showed and confirmed at histological and IHC levels. Molecular analysis showed an HPV infection in the carcinoma. Additionally, sequencing results revealed common (CDKN2A and TERT) and exclusive (FBXW7 and TP53) genetic alterations in both tumors (Table 1). The possible germline origin of common mutations was discarded after negative germline testing. Here we describe, for the first time a clinical case of a possible origin of two histologically different tumors from a common ancestor based on molecular data. Even if different hypothesis appear as possible, the Cancer Stem Cell-based model appears as the most suitable.

Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis.

Aim: Darolutamide significantly prolonged metastasis-free survival (MFS) versus placebo in the Phase III ARAMIS study. We analyzed outcomes in Spanish participants in ARAMIS. Patients & methods: Patients with high-risk nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus androgen-deprivation therapy. The primary end point was MFS. Descriptive statistics are reported for this post hoc analysis. Results: In Spanish participants, darolutamide (n = 75) prolonged MFS versus placebo (n = 42): hazard ratio 0.345, 95% confidence interval 0.175-0.681. The incidence and type of treatment-emergent adverse events were comparable between treatment arms. Conclusion: For Spanish participants in ARAMIS, efficacy outcomes favored darolutamide versus placebo, with a similar safety profile, consistent with the overall ARAMIS population. Clinical Trials Registration: NCT02200614 (ClinicalTrials.gov).

Darolutamide is an oral treatment for a type of prostate cancer that has stopped responding to other treatments and is at risk of spreading to other parts of the body (termed "nonmetastatic castration-resistant prostate cancer" or "nmCRPC"). In the international ARAMIS study, patients treated with darolutamide lived longer without their cancer spreading than patients who were given placebo (sugar) pills. We wanted to know whether Spanish patients in ARAMIS had similar characteristics and treatment outcomes to other patients in the study. We found that the 75 Spanish patients who were treated with darolutamide had a significantly lower risk of their cancer spreading than the 42 Spanish patients who received placebo. The two groups of Spanish patients had similar side effects.

Free-indocyanine green-guided pelvic lymph node dissection during radical prostatectomy.

INTRODUCTION AND OBJECTIVES: Extended Pelvic Lymph Node Dissection (ePLND) remains the most accurate technique for the detection of occult lymph node metastases (LNMs) in prostate cancer (CaP) patients. Here we aim to examine whether free-Indocyanine Green (F-ICG) could accurately assess the pathological nodal (pN) status in CaP patients during real-time lymphangiography as a potential replacement for ePLND. MATERIALS AND METHODS: 219 consecutive patients undergoing F-ICG-guided PLND, ePLND and radical prostatectomy (RP) for clinical-localized CaPwere included in this prospective single-center study. The pathological outcomes of F-ICG-guided PLND were compared to confirmatory ePLND. Parameters of a binary diagnostic test for the proper classification of the pN status of patients ('per-patient' analysis) and for the probability of detecting all the metastatic LNs ('per-node' analysis) were calculated. Outcome measures were prevalence, accuracy (Acc), sensitivity (Se), negative predictive value (NPV), and likelihood ratio of a negative F-ICG-guided PLND test result [LR(-)]. RESULTS: F-ICG-guided PLND successfully visualized LNs in all procedures with no adverse events. The overall per-patient F-ICG staging Acc was 97.7%, Se was 91.4%, with a NPV of 97.0%, and LR(-) of 8.6%. At the overall per-node level, 4,780 LNs were removed and 1,535 (32.1%) were fluorescent in vivo. F-ICG-guided PLND identified LNMs with a Se of 63.4%. CONCLUSIONS: This study confirms that F-ICG-guided lymphangiography correctly staged almost 98% of patients. The high per-patient NPV suggested that avoiding ePLND is safe for most patients when F-ICG stained nodes were pN0. Thus, more conservative approaches might minimise perioperative morbidity during LNMs diagnosis in selected patients.

Bilateral Seminal Vesicle Invasion Is Not Associated with Worse Outcomes in Locally Advanced Prostate Carcinoma.

Background and Objectives: Patients with seminal vesicle invasion (SVI) are a highly heterogeneous group. Prognosis can be affected by many clinical and pathological characteristics. Our aim was to study whether bilateral SVI (bi-SVI) is associated with worse oncological outcomes. Materials and Methods: This is an observational retrospective study that included 146 pT3b patients treated with radical prostatectomy (RP). We compared the results between unilateral SVI (uni-SVI) and bi-SVI. The log-rank test and Kaplan-Meier curves were used to compare biochemical recurrence-free survival (BCR), metastasis-free survival (MFS), and additional treatment-free survival. Cox proportional hazard models were used to identify predictors of BCR-free survival, MFS, and additional treatment-free survival. Results: 34.93% of patients had bi-SVI. The median follow-up was 46.84 months. No significant differences were seen between the uni-SVI and bi-SVI groups. BCR-free survival at 5 years was 33.31% and 25.65% (p = 0.44) for uni-SVI and bi-SVI. MFS at 5 years was 86.03% vs. 75.63% (p = 0.1), and additional treatment-free survival was 36.85% vs. 21.93% (p = 0.09), respectively. In the multivariate analysis, PSA was related to the development of BCR [HR 1.34 (95%CI: 1.01-1.77); p = 0.03] and metastasis [HR 1.83 (95%CI: 1.13-2.98); p = 0.02]. BCR was also influenced by lymph node infiltration [HR 2.74 (95%CI: 1.41-5.32); p = 0.003]. Additional treatment was performed more frequently in patients with positive margins [HR: 3.50 (95%CI: 1.65-7.44); p = 0.001]. Conclusions: SVI invasion is an adverse pathology feature, with a widely variable prognosis. In our study, bilateral seminal vesicle invasion did not predict worse outcomes in pT3b patients despite being associated with more undifferentiated tumors.

Indocyanine green guidance improves the efficiency of extended pelvic lymph node dissection during laparoscopic radical prostatectomy.

OBJECTIVES: To evaluate whether indocyanine green guidance can improve the quality of extended pelvic lymph node dissection in patients undergoing radical prostatectomy. METHODS: A total of 214 patients underwent laparoscopic radical prostatectomy with indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection. These patients (group A) were matched 1:1 for clinical risk groups according to the National Comprehensive Cancer Network classification with patients who underwent the same procedure without fluorescence guidance (group B). Biochemical recurrence was defined as two consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan-Meier method and Cox regression models were used to identify predictors of biochemical recurrence. RESULTS: The median number of retrieved nodes was significantly higher in group A (22 vs 14, P < 0.001). The rate of lymph node metastases was higher in group A (65.9% vs 34.1%, P = 0.01). Increasing the yield of lymph node dissection was independently and negatively correlated with the biochemical recurrence risk in both overall and pN-positive patients (hazard ratio 0.97, P = 0.03; and hazard ratio 0.95, P = 0.02). The 5-year biochemical recurrence-free survival rates were (75.8% vs 65.9, P = 0.09) and (54.1% vs 24.9%, P = 0.023) for group A and group B in the overall cohort and pN-positive cohort, respectively. CONCLUSION: Indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection improves identification of lymphatic drainage, resulting in a higher number of lymph nodes and retrieved lymph node metastases, and allowing a more accurate local staging and a prolonged biochemical recurrence-free survival.

Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.

Ex-vivo confocal fluorescence microscopy for rapid evaluation of renal core biopsy.

Small renal mass incidentally diagnosed are common findings nowadays due to the widespread of imaging. Renal mass biopsy is still underutilized by urologists due to its non-diagnostic rates. Confocal microscopy allows for rapid imaging of fresh tissue samples. We report the feasibility of using confocal technology for determining the quality of the renal core at renal mass biopsy on 4 consecutive cases at our institution.

[ICG lymphography and fluorescence in pelvic lymphadenectomy for bladder and prostate cancer.] / Linfografía con ICG y fluorescencia en la linfadenectomía pélvica por cáncer vesical y prostático.

OBJECTIVE: ICG navigation in cancer surgery may help during pelvic lymphadenectomy. METHODS: We performed a systematic review combining the terms: bladder cancer or radical cystectomy and ICG, and prostate cancer or radical prostatectomy and ICG. We used the PRISMA guidelines recommendations. We describe the populations studied in each work, the pathological results, as well as the parameters specificity, sensitivity and predictive values. RESULTS: In muscle-invasive bladder cancer, 4 case series analyzed the performance of lymphography with ICG. The most accepted injection method is under endoscopic vision. Several punctures are done in the submucosa and the detrusor surrounding the scar. Sentinel nodes were found in up to 92% of patients with a technique sensitivity to find metastases of 88% in the series with largest casuistry. In prostate cancer, we collected data from 11 case series. Nine of them apply transrectal or transperineal dilution immediately before surgery. Sensitivity in the detection of all adenopathies ranged between 44% and 100%. The sensitivity of the technique to know the lymph node stage ranges between 67% and 100%. CONCLUSIONS: There is little experience of ICG-guided lymph node dissedction in bladder tumors. Endoscopic fluorophore injection allows us to find the nodes that drain the infiltrated area. However, the use of this technique is not widespread. In prostate cancer, it is a reproducible and efficient technique for staging patients with prostate cancer.

OBJETIVO: La principal aplicación del ICG en cirugía oncológica es la navegación intraoperatoria durante la linfadenectomía. Revisamos la literatura para conocer el uso de ICG durante la linfadenectomía pélvica en el cáncer de próstata y cáncer de vejiga.MATERIAL Y MÉTODO: Hacemos una revisión sistemática con los términos cáncer de vejiga o cistectomía radical, cáncer de próstata o prostatectomía radical. Utilizamos las recomendaciones de las guías PRISMA. Describimos las poblaciones a estudio en cada trabajo, los resultados patológicos así como los parámetros sensibilidad especificidad y valores predictivos. RESULTADOS: En tumor vesical musculo invasivo 4 series de casos analizan el rendimiento de la linfografia con ICG. El método de inyección más aceptado es la inyección de la dilución -bajo visión endoscópica- en la submucosa y en el detrusor, peri tumoral o pericicatrical. Se encontraron ganglios centinela hasta en el 92% de los pacientes con una sensibilidad de la técnica para encontrar las metástasis del 88% en la serie de mayor casuística. En cáncer de próstata recopilamos datos de 11 series. De entre ellas 9 aplican la dilución vía transrectal o transperineal inmediatamente antes de la cirugía. La sensibilidad en la detección de todas las adenopatías oscila entre el 44 y el 100%. En cuanto la sensibilidad de la técnica para conocer el estadio ganglionar oscila entre el 67% y el 100%. CONCLUSIONES: Existe poca experiencia de la linfadenectomía guiada por ICG en tumor de vejiga. La inyección endoscópica del fluoróforo permite encontrar los ganglios que drenan el área infiltrada, sin embargo no se populariza el uso de esta técnica. El cáncer de próstata es una técnica reproducible y eficiente para estadiar a los pacientes con cáncer de próstata.

Linfografía con ICG y fluorescencia en la linfadenectomía pélvica por cáncer vesical y prostático / ICG lymphography and fluorescence in pelvic lymphadenectomy for bladder and prostate cancer

Objetivo: La principal aplicación del ICG en cirugía oncológica es la navegación intraoperatoria durante la linfadenectomía. Revisamos la literatura para conocer el uso de ICG durante la linfadenectomía pélvica en el cáncer de próstata y cáncer de vejiga. Material y método: Hacemos una revisión sistemática con los términos cáncer de vejiga o cistectomía radical, cáncer de próstata o prostatectomía radical. Utilizamos las recomendaciones de las guías PRISMA. Describimos las poblaciones a estudio en cada trabajo, los resultados patológicos así como los parámetros sensibilidad especificidad y valores predictivos. Resultados: En tumor vesical musculo invasivo 4 series de casos analizan el rendimiento de la linfografia con ICG. El método de inyección más aceptado es la inyección de la dilución -bajo visión endoscópica- en la submucosa y en el detrusor, peri tumoral o pericicatrical. Se encontraron ganglios centinela hasta en el 92% de los pacientes con una sensibilidad de la técnica para encontrar las metástasis del 88% en la serie de mayor casuística. En cáncer de próstata recopilamos datos de 11 series. De entre ellas 9 aplican la dilución vía transrectal o transperineal inmediatamente antes de la cirugía. La sensibilidad en la detección de todas las adenopatías oscila entre el 44 y el 100%. En cuanto la sensibilidad de la técnica para conocer el estadio ganglionar oscila entre el 67% y el 100%. Conclusiones: Existe poca experiencia de la linfadenectomía guiada por ICG en tumor de vejiga. La inyección endoscópica del fluoróforo permite encontrar los ganglios que drenan el área infiltrada, sin embargo no se populariza el uso de esta técnica. El cáncer de próstata es una técnica reproducible y eficiente para estudiar a los pacientes con cáncer de próstata

Objective: ICG navigation in cancer surgery may help during pelvic lymphadenectomy. Methods: We performed a systematic review combining the terms: bladder cancer or radical cystectomy and ICG, and prostate cancer or radical prostatectomyand ICG. We used the PRISMA guidelines recommendations. We describe the populations studied in each work, the pathological results, as well as the parameters specificity, sensitivity and predictive values. Results: In muscle-invasive bladder cancer, 4 case series analyzed the performance of lymphography with ICG. The most accepted injection method is under endoscopic vision. Several punctures are done in the submucosa and the detrusor surrounding the scar. Sentinel nodes were found in up to 92% of patients with a technique sensitivity to find metastases of 88% in the series with largest casuistry. In prostate cancer, we collected data from 11 case series. Nine of them apply transrectal or transperineal dilution immediately before surgery. Sensitivity in the detection of all adenopathies ranged between 44% and 100%. The sensitivity of the technique to know the lymph node stage ranges between 67% and 100%. Conclusions: There is little experience of ICG-guided lymph node dissedction in bladder tumors. Endoscopic fluorophore injection allows us to find the nodes that drain the infiltrated area. However, the use of this technique is not widespread. In prostate cancer, it is a reproducible and efficient technique for staging patients with prostate cancer

Long-term functional outcome and complications of male suburethral slings in the management of post-prostatectomy incontinence: A prospective five-year follow-up study.

OBJECTIVES: Suburethral male slings are an alternative option for mild stress urinary incontinence. Our purpose is to evaluate the long-term functional outcomes, efficacy and worsening continence of male suburethral slings. MATERIAL AND METHODS: The functional outcomes of realignment/anatomical slings were evaluated with AdVance ®, and the outcomes of compressive slings were evaluated with InVance®. We considered 55 patients fulfilling 5 years of complete follow-up. We included patients with a 24-hour pad weight test <400 grams. Night-continent patients who also had positive "repositioning tests" were considered for AdVance®, whereas patients without sphincter contraction or previous pelvic radiotherapy were considered for InVance®. RESULTS: Between February 2006 and September 2010, 24 AdVance® and 31 InVance® slings were implanted. The median follow-up times from sling insertion were 75 months in the AdVance® group (range: 64-97) and 86 months in the InVance® group (range: 61-108). At three months of follow-up, 43 of 55 patients were considered to be cured (pad-free) (78.1%), 79.1% in the AdVance® group and 77.4% in the InVance® group. Postoperatively, 16.6% of patients with AdVance® and 22.5% of patients with InVance® presented "de novo" urgency. At 5 years of follow-up, we observed 10 cases of some deterioration of continence, 3 patients in the AdVance® group and 7 in the InVance® group (15.8% and 29.1% of the initially cured, respectively). To date, there have been no reports of urethral sling erosion. CONCLUSIONS: Male slings are safe and effective. Although we observed an increase in "de novo" urgency, in our experience, slings seemed to maintain their efficacy during long-term follow-up, and the risks of urethral erosion are low.

OBJETIVOS: Los cabestrillos suburetrales masculinos son una opción alternativa para la incontinencia urinaria de esfuerzo leve. El objetivo del trabajo es evaluar los resultados funcionales a largo plazo, la eficacia y el empeoramiento de la continencia en los cabestrillos suburetrales masculinos. METODOS: Se evaluaron los resultados funcionales de los cabestrillos de realineamiento/anatómicos con Ad- Vance® y compresivos con InVance®. Se incluyeron 55 pacientes que cumplían con los 5 años de seguimiento completo. Incluimos pacientes con un peso en el test de la compresa de 24 h menor de 400 gramos. Los pacientes con continencia nocturna que tenían también positivas las pruebas de reposicionamiento se consideraron para AdVance®, mientras que los pacientes sin contracción esfinteriana o con radioterapia pélvica previa fueron considerados para InVance®. RESULTADOS: Entre febrero 2006 y septiembre 2010 se implantaron 24 cabestrillos AdVance® y 31 InVance ®. La mediana de seguimiento fue de 75 meses desde la inserción del cabestrillo en el grupo de AdVance® (rango 64-97) y 86 meses en el grupo de InVance® (rango: 61-108). A los tres meses de seguimiento, 43 de los 55 pacientes fueron considerados curados (sin compresa) (78,1%), 79,1% en el grupo de AdVance® y 77,4% en el de InVance®. En el postoperatorio, el 16,6% de los pacientes con AdVance® y el 22,5% de los InVance® presentaron urgencia "de novo". A los 5 años de seguimiento, observamos 10 casos con algún deterioro de la continencia, 3 pacientes en el grupo de AdVance® y 7 en el de InVance® (15,8% y 29,1% de los pacientes inicialmente curados, respectivamente). Hasta la fecha, no se han presentado casos de erosión del cabestrillo. CONCLUSIONES: Los cabestrillos masculinos son seguros y eficaces. Aunque observamos un incremento de la urgencia "de novo", en nuestra experiencia, los cabestrillos parecen mantener su eficacia durante el seguimiento a largo plazo, y los riesgos de erosión uretral son bajos.

Long-term functional outcome and complications of male suburethral slings in the management of post-prostatectomy incontinence: a prospective five-year follow-up study / Resultados funcionales a largo plazo y complicaciones de los cabestrillos suburetrales masculinos en el manejo de la incontinencia postprostatectomía: estudio prospectivo con seguimiento a cinco años

Objectives: Suburethral male slings are an alternative option for mild stress urinary incontinence. Our purpose is to evaluate the long-term functional outcomes, efficacy and worsening continence of male suburethral slings. Material and methods: The functional outcomes of realignment/anatomical slings were evaluated with AdVance(R), and the outcomes of compressive slings were evaluated with InVance(R). We considered 55 patients fulfilling 5 years of complete follow-up. We included patients with a 24-hour pad weight test < 400 grams. Night-continent patients who also had positive "reposi-tioning tests" were considered for AdVance(R), whereas patients without sphincter contraction or previous pelvic radiotherapy were considered for InVance(R). RESULTS: Between February 2006 and September 2010, 24 AdVance(R) and 31 InVance(R) slings were implanted. The median follow-up times from sling insertion were 75 months in the AdVance(R) group (range: 64-97) and 86 months in the InVance(R) group (range: 61-108). At three months of follow-up, 43 of 55 patients were considered to be cured (pad-free) (78.1%), 79.1% in the AdVance(R) group and 77.4% in the InVance(R) group. Postoperatively, 16.6% of patients with AdVance(R) and 22.5% of patients with InVance(R) presented "de novo" urgency. At 5 years of follow-up, we observed 10 cases of some deterioration of continence, 3 patients in the AdVance(R) group and 7 in the InVance(R) group (15.8% and 29.1% of the initially cured, respectively). To date, there have been no reports of urethral sling erosion. Conclusions: Male slings are safe and effective. Although we observed an increase in "de novo" urgency, in our experience, slings seemed to maintain their efficacy during long-term follow-up, and the risks of urethral erosion are low

Objetivos: Los cabestrillos suburetrales masculinos son una opción alternativa para la incontinencia urinaria de esfuerzo leve. El objetivo del trabajo es evaluar los resultados funcionales a largo plazo, la eficacia y el empeoramiento de la continencia en los cabestrillos suburetrales masculinos. Metodos: Se evaluaron los resultados funcionales de los cabestrillos de realineamiento/anatómicos con Ad- Vance(R) y compresivos con InVance(R). Se incluyeron 55 pacientes que cumplían con los 5 años de seguimiento completo. Incluimos pacientes con un peso en el test de la compresa de 24 h menor de 400 gramos. Los pacientes con continencia nocturna que tenían también positivas las pruebas de reposicionamiento se consideraron para AdVance(R), mientras que los pacientes sin contracción esfinteriana o con radioterapia pélvica previa fueron considerados para InVance(R). Resultados: Entre febrero 2006 y septiembre 2010 se implantaron 24 cabestrillos AdVance(R) y 31 InVance(R). La mediana de seguimiento fue de 75 meses desde la inserción del cabestrillo en el grupo de AdVance(R) (rango 64-97) y 86 meses en el grupo de InVance(R) (rango: 61-108). A los tres meses de seguimiento, 43 de los 55 pacientes fueron considerados curados (sin compresa) (78,1%), 79,1% en el grupo de AdVance(R) y 77,4% en el de InVance(R). En el postoperatorio, el 16,6% de los pacientes con AdVance(R) y el 22,5% de los InVance(R) presentaron urgencia "de novo". A los 5 años de seguimiento, observamos 10 casos con algún deterioro de la continencia, 3 pacientes en el grupo de AdVance(R) y 7 en el de InVance(R) (15,8% y 29,1% de los pacientes inicialmente curados, respectivamente). Hasta la fecha, no se han presentado casos de erosión del cabestrillo. Conclusiones: Los cabestrillos masculinos son seguros y eficaces. Aunque observamos un incremento de la urgencia "de novo", en nuestra experiencia, los cabestrillos parecen mantener su eficacia durante el seguimiento a largo plazo, y los riesgos de erosión uretral son bajos

Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance.

BACKGROUND: Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months. METHODS: Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA ≤10 ng/mL, cT1c-T2a, Grade group 1, ≤2 cores, and ≤5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group ≥2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher's exact test, as appropriate established differences between groups of reclassification. RESULTS: A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume. CONCLUSIONS: Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management.

Prospective follow-up study of artificial urinary sphincter placement preserving the bulbospongiosus muscle.

AIMS: Artificial urinary sphincter (AUS) AMS-800® is an effective treatment for male stress urinary incontinence. The aim of the study was to assess the long-term effectiveness and complications of artificial urinary sphincter placement preserving the bulbospongiosus muscle. METHODS: From April 2004 to March 2014, all consecutive male patients with urinary incontinence who underwent an AUS prosthesis insertion were prospectively evaluated. Surgical technique consisted of a perineal incision for cuff placement around the bulbous urethra preserving the bulbospongiosus muscle. Cure rate was defined as no pad use. RESULTS: A total of 82 consecutive patients (median age 68 years, range: 54-78) were prospectively evaluated (median follow-up 46 months, range: 12-135). Bulbospongiosus muscles were preserved intact in all cases with no intraoperative complications. Postoperative complications were reported in 14 patients (1 urethral erosion). The overall cure rate (dry rate) was 76.8% and the median ICIQ-UI score improved from 18 (range: 8-21) to 4 (range: 0-17) (P < 0.001). Artificial urinary sphincter survival rate was 95.5% (95%CI 89.4-100%) at 24 months and 62.6% (95%CI 45.5-79.6%) at 60 months. The mechanical failure rate was 6.3% (median 46.1 months, range: 22.2-100.9) and urethral atrophy and/or inadequate compression rate was 9.5% (median 58.6 months, range: 39-101.4 months). CONCLUSIONS: Our study suggests that placement of AUS preserving the bulbospongiosus muscle is technically easy and efficient, reports excellent continence rates and lower urethral erosion rates, and could delay the onset of urethral atrophy compared to other surgical procedures used for sphincter placement.

Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: a Spanish expanded access trial.

BACKGROUND: Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML. METHODS: This was a Spanish expanded access trial including patients aged ≥18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC-related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy. RESULTS: Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3-10.9) months. Eleven (57.9 %) remained on 10 mg/day throughout the study and eight (42.1 %) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1 %) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3 %) was serious (pneumonia). AML volume was reduced ≥30 % in 11 (57.9 %) patients and ≥50 % in 9 (47.4 %); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively. CONCLUSIONS: These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes. TRIAL REGISTRATION: EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PURPOSE: We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. MATERIALS AND METHODS: A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. RESULTS: A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. CONCLUSIONS: Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis.