Ultralow Prostate-Specific Antigen (PSA) Levels and Improved Oncological Outcomes in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Patients Treated with Apalutamide: A Real-World Multicentre Study.

Background/Objectives: Androgen receptor-targeted agents have significantly improved the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific antigen (PSA) levels are key prognostic markers, with rapid and deep reductions associated with better outcomes. This study aims to assess the association between the new PSA cut-offs and survival in mHSPC patients treated with Apalutamide. Methods: We conducted a multicentre, retrospective analysis of mHSPC patients treated with Apalutamide between March 2021 and January 2023. Overall survival (OS) and radiographic progression-free survival (rFPS) were analyzed and stratified by the following PSA ranges: <0.02 ng/mL (ultralow), 0.02-0.2 ng/mL, and >0.2 ng/mL. Cox regression was applied to identify variables associated with OS and rPFS. Results: Among 193 patients, 34.2% had de novo mHSPC, with the majority classified as M1b. A total of 58.2% (110) of our cohort achieved ultralow PSA levels, with 20.6% between 0.02 and 0.2 ng/mL, and 21.2% of PSA levels > 0.2 ng/mL. Most patients reached ultralow PSA within six months. Low-volume, metachronous, and M1a subgroups displayed a higher prevalence of patients reaching ultralow PSA levels. At 18 months, OS was 100% in the ultralow PSA group, 94.4% for the 0.02-0.2 ng/mL group, and 67.7% in the >0.2 ng/mL group. Similarly, rPFS at 18 months was 100%, 93.5%, and 50.7%, respectively. Cox regression revealed that both ultralow PSA levels and ISUP grade had a significant impact on OS (HR of 8.256 and 0.164, respectively). For rPFS, only ultralow PSA levels had a significant impact (HR = 0.085). Conclusions: This real-world study of mHSPC patients treated with Apalutamide plus ADT revealed that achieving ultralow PSA levels is strongly associated with better oncological outcomes.

Comparative evaluation of continence and potency after radical prostatectomy: Robotic vs. laparoscopic approaches, validating LAP-01 trial.

BACKGROUND: Minimally invasive techniques have demonstrated several advantages over the open approach. In the field of prostate cancer, the LAP-01 trial demonstrated the superiority of robotic-assisted radical prostatectomy (RARP) over laparoscopic radical prostatectomy (LRP) when comparing continence at 3-month after surgery, with no statistically significant differences at 6 and 12 months of follow-up. OBJECTIVES: Externally validate the LAP-01 study and compare functional outcomes between the two minimally invasive approaches. MATERIAL AND METHODS: This retrospective study, conducted by a single surgeon (MRB), utilized data from a prospectively collected database, which included patients who underwent both RARP or LRP. Data regarding baseline characteristics, continence (assessed through the 24-h Pad test and ICIQ questionnaire) and potency were collected at multiple time points: 1 and 6 weeks after catheter removal, 3-, 6-, and 12-months post-surgery. RESULTS: The study encompasses 601 patients, 455 who underwent LRP and 146 RARP. The median age at diagnosis was 64 for LRP and 62 for RARP, while the median PSA levels at diagnosis were 6.7 ng/mL for LRP and 6.5 ng/mL for RARP. Bilateral nerve-sparing procedures were performed in 34.07 % of LRP cases and 51.37 % of RARP cases. RARP exhibited a significant advantage over LRP both in continence and potency. Continence rates at 3-, 6- and 9-month after radical prostatectomy (RP) were 36.43 %, 61.86 % and 79.87 % for LRP, compared to 50.98 %, 69.87 % and 91.69 % for RARP. Potency rates at the same intervals were 0.90 %, 3.16 % and 6.39 % for LRP, and 6.19 %, 9.16 % and 18.96 % for RARP. These rates were more pronounced in patients with bilateral nerve-sparing. CONCLUSION: Our study demonstrates that RARP results in significantly better continence recovery and superior potency outcomes throughout the entire follow-up period compared to LRP, even at the beginning of the robotic approach learning curve.

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. To date, extended pelvic LN dissection remains the gold standard for N-staging and cannot be replaced yet by unilateral pelvic LN dissection until high quality evidence supports this scenario.

Real-world prostate-specific antigen reduction and survival outcomes of metastatic hormone-sensitive prostate cancer patients treated with apalutamide: An observational, retrospective, and multicentre study.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.

BACKGROUND: Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown. METHODS: In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety. RESULTS: A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures. CONCLUSIONS: In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

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.

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers.

BACKGROUND: Several studies have reported the association of germline BRCA2 (gBRCA2) mutations with poor clinical outcomes in prostate cancer (PCa), but the impact of concurrent somatic events on gBRCA2 carriers survival and disease progression is unknown. PATIENTS AND METHODS: To ascertain the role of frequent somatic genomic alterations and histology subtypes in the outcomes of gBRCA2 mutation carriers and non-carriers, we correlated the tumour characteristics and clinical outcomes of 73 gBRCA2 and 127 non-carriers. Fluorescent in-situ hybridisation and next-generation sequencing were used to detect copy number variations in BRCA2, RB1, MYC and PTEN. Presence of intraductal and cribriform subtypes was also assessed. The independent impact of these events on cause-specific survival (CSS), metastasis-free survival and time to castration-resistant disease was assessed using cox-regression models. RESULTS: Somatic BRCA2-RB1 co-deletion (41% versus 12%, p < 0.001) and MYC amplification (53.4% versus 18.8%, p < 0.001) were enriched in gBRCA2 compared to sporadic tumours. Median CSS from diagnosis of PCa was 9.1 versus 17.6 years in gBRCA2 carriers and non-carriers, respectively (HR 2.12; p = 0.002), Median CSS in gBRCA2 carriers increased to 11.3 and 13.4 years in the absence of BRCA2-RB1 deletion or MYC amplification, respectively. Median CSS of non-carriers decreased to 8 and 2.6 years if BRCA2-RB1 deletion or MYC amplification were detected. CONCLUSIONS: gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.

Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer.

BACKGROUND: EMBARK, a controlled trial reported elsewhere, showed enzalutamide plus leuprolide (combination) and enzalutamide monotherapy prolonged metastasis-free survival versus placebo plus leuprolide (alone) in patients with high-risk biochemically recurrent prostate cancer. Health-related quality of life was also analyzed but not reported. METHODS: In EMBARK, patients with biochemical recurrence (prostate-specific antigen doubling time of ≤9 months) were randomly assigned (1:1:1) to combination (n=355), leuprolide-alone (n=358), or enzalutamide monotherapy (n=355). In this article we provide the patient-reported outcomes (PROs) from EMBARK at baseline and every 12 weeks until metastasis or death. The key end point was time to first and confirmed clinically meaningful deterioration (TTFD/TTCD) in pain and health-related quality of life using four PRO measures and predefined thresholds. RESULTS: At baseline, all groups had high health-related quality of life. For worst pain, the median TTFD was 19.35 months with leuprolide alone, 13.93 months with combination (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.30) and 16.59 months with monotherapy (hazard ratio, 1.09; 95% CI, 0.90 to 1.31). The median TTCD was 66.27 months with leuprolide alone, 80.00 months with combination (hazard ratio, 0.82; 95% CI, 0.65 to 1.04), and 60.91 months with monotherapy (hazard ratio, 1.02; 95% CI, 0.82 to 1.28). For Functional Assessment of Cancer Therapy­Prostate total score, the median TTFD was 11.10 months with leuprolide alone, 8.31 months with combination (hazard ratio, 1.14; 95% CI, 0.95 to 1.36), and 8.38 months with monotherapy (hazard ratio, 1.17; 95% CI, 0.98 to 1.39). The median TTCD was 36.53 months with leuprolide alone, 38.77 months with combination (hazard ratio, 1.04; 95% CI, 0.85 to 1.28), and 30.55 months with monotherapy (hazard ratio, 1.16; 95% CI, 0.95 to 1.41). CONCLUSIONS: The PROs from EMBARK show that both enzalutamide combination and monotherapy versus leuprolide alone, with oncologic benefits noted above, preserved high health-related quality of life in patients with high-risk biochemical recurrence of prostate cancer. (Funded by Pfizer and Astellas Pharma; ClinicalTrials.gov number, NCT02319837.)

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.

Prognostic Impact of Sarcopenia in Patients with Advanced Prostate Carcinoma: A Systematic Review.

Prostate cancer (PCa) is the second most common cancer in men and the fifth leading cause of death from cancer. The possibility of sarcopenia being a prognostic factor in advanced PCa patients has recently become a subject of interest. The aim of the present study was to evaluate the prognostic value of sarcopenia in advanced prostate carcinoma. A systematic review was conducted in Medline, EMBASE, and Web of Science (March, 2021). The quality of studies was assessed using the Quality in Prognosis Studies tool. Meta-analyses for overall, cancer-specific, and progression-free survival were performed. Nine studies (n = 1659) were included. Sarcopenia was borderline associated with a shorter overall survival (HR = 1.20, 95% CI: 1.01, 1.44, P = 0.04, I2 = 43%) but was significantly associated with progression-free survival (HR = 1.61, 95% CI: 1.26, 2.06, P < 0.01; k = 3; n = 588). Available evidence supports sarcopenia as an important prognostic factor of progression-free survival in patients with advanced PCa. However, sarcopenia has a weak association with a shorter overall survival. The evidence on the role of sarcopenia in prostate-cancer-specific survival is insufficient and supports the need for further research. Patient summary: The literature was reviewed to determine whether the loss of muscle mass (sarcopenia) affects the survival in patients with advanced PCa. Patients with advanced PCa and sarcopenia were found to have a shorter progression-free survival (the length of time during and after treatment of a cancer that the patient lives with the disease but it does not get worse), but sarcopenia did not have much influence on the overall survival and cancer-specific survival (the length of time from either the date of diagnosis or the start of treatment to the date of death due to the cancer).

Clinicopathological and Molecular Prognostic Classifier for Intermediate/High-Risk Clear Cell Renal Cell Carcinoma.

The probability of tumor progression in intermediate/high-risk clear cell renal cell carcinoma (ccRCC) is highly variable, underlining the lack of predictive accuracy of the current clinicopathological factors. To develop an accurate prognostic classifier for these patients, we analyzed global gene expression patterns in 13 tissue samples from progressive and non-progressive ccRCC using Illumina Hi-seq 4000. Expression levels of 22 selected differentially expressed genes (DEG) were assessed by nCounter analysis in an independent series of 71 ccRCCs. A clinicopathological-molecular model for predicting tumor progression was developed and in silico validated in a total of 202 ccRCC patients using the TCGA cohort. A total of 1202 DEGs were found between progressive and non-progressive intermediate/high-risk ccRCC in RNAseq analysis, and seven of the 22 DEGs selected were validated by nCounter. Expression of HS6ST2, pT stage, tumor size, and ISUP grade were found to be independent prognostic factors for tumor progression. A risk score generated using these variables was able to distinguish patients at higher risk of tumor progression (HR 7.27; p < 0.001), consistent with the results obtained from the TCGA cohort (HR 2.74; p < 0.002). In summary, a combined prognostic algorithm was successfully developed and validated. This model may aid physicians to select high-risk patients for adjuvant therapy.

Rebiopsy rate after transperineal or transrectal prostate biopsy.

BACKGROUND: In recent years, transperineal biopsies gained popularity for prostate cancer diagnosis; lower infective complications and improved sampling of the prostate are the main advantages of this technique. One question that remains unclear is whether an initial transperineal biopsy confers a lower risk for rebiopsy compared with the transrectal approach. METHODS: Six hundred seventy-one men were prospectively followed after an initial negative prostate biopsy for a median period of 49.50 (IQR: 37.62-61.17) months. Rebiopsy rate was analyzed attending to first biopsy approach (transrectal versus transperineal systematic) and clinical variables. RESULTS: Diagnostic rate was similar for transrectal and transperineal systematic biopsies. Targeted biopsies outperformed any systematic approach, and transperineal targeted in particular was superior to transrectal targeted. Rebiopsy rates were 15.4% and 5.26% for the transrectal and transperineal systematic groups, respectively. Prostate-specific antigen density and type of first biopsy were identified as rebiopsy predictors. CONCLUSION: Men undergoing transperineal systematic biopsies had a three times lower rate of rebiopsy over the study period compared with the traditional transrectal approach. This advantage could be added to the already described potential benefits of transperineal biopsies. Targeted biopsies had lower rebiopsy rate over the study period. Further innovations that decreased the cost of transperineal biopsies could favor this approach in the future.

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.

Pelvic lymph node distribution and metastases of prostate and bladder cancer: a systematic literature review and template proposal.

PURPOSE: To systematically review the relevant literature that evaluates the LN topographical distribution and propose a uniform template. METHODS: A bibliographic search of PubMed/Medline, Embase and SCOPUS was performed for studies reporting data of LN imaging and/or nodal resection. RESULTS: 101 and 26 articles met the inclusion criteria for PCa and BCa, respectively. In PCa, the most common locations of positive LNs for surgical and imaging studies were external iliac (both 38 studies), followed by obturator (38 and 37, respectively). Similarly, in BCa, the most common location of positive nodes for surgical and imaging studies were external iliac (19 and 4, respectively), followed by obturator (15 and 3 studies, respectively). In PCa, median percentages of positive external iliac nodes/patient were 12.2% and 11.6% for surgical and imaging studies, respectively while corresponding rates for BCa were 3.9% and 17.6%. There were high risks of bias across studies as well as high heterogeneity in the definition of the anatomic boundaries of lymphadenectomy templates. CONCLUSIONS: This review highlights the lack of detailed information on exact LN templates and metastases location, which in turn hinders generation of high-quality evidence on optimal lymphadenectomy templates. Our proposed template is applicable for both imaging and surgical description and could facilitate the translation of anatomical location from imaging to surgical resection.

[Prostate cancer and COVID-19 pandemia: Current recommendations.] / Cáncer de próstata y la pandemia Covid-19. Recomendaciones ante una nueva realidad.

OBJECTIVE: The objective of this publicationis to provide recommendations in the management of prostate cancer (PC) in a new reality framework based on the presence of COVID-19 disease. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in handling COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Catalonia, Madrid and the Valencian Community. RESULTS: The authors defined different priorities for the different clinical situations in PC. Emergency/urgency (life-threatening or urgent even in normal situation), highpriority/elective urgency (potentially dangerous if postponed for more than 1 month), intermediate/electivepriority (it is recommended not to delay more than 6 months), low priority/delayed (can be postponed more than 6 months). According to this classification, the working panel agreed on the distribution of the different diagnostic, therapeutic and follow-up scenarios for PC. The risk of severe morbidity as a result of SARS-CoV-2 infection may out weigh the risk of PC morbidity/mortalityin many men; therefore, in the short term it is unlikely that delays in diagnosis or treatment can led to worse cancer outcomes. CONCLUSIONS: The COVID-19 pandemic has resulted in a challenge for our health system, which raises several considerations in the treatment of patients with PC. The redistribution of surgical procedures according to the degrees of priority is essential during the period of the pandemic and the transition to the new normality. The change of the out-clinics with the adequate security measures for healthcare practitioners and patients, andt he development of a telemedicine program is highly recommended.

OBJETIVO: El objetivo de esta publicaciónes proporcionar recomendaciones en el manejo del cáncer de próstata (CP) en el marco de la nueva realidad que supone la presencia de la COVID-19.MATERIALES Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/CoV-2 y la experiencia de los autores en el manejo de la COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Cataluña, Madrid y Comunidad Valenciana. RESULTADOS: Los autores definieron diferentes prioridades para los distintos supuestos clínicos en CP. Emergencia/urgencia (riesgo vital o urgencia aún en situación de normalidad), alta prioridad/urgencia electiva (potencialmente peligrosa si se pospone más de 1mes), prioridad intermedia/electiva (se recomienda no retrasar más de 6 meses), baja prioridad/demorable (se puede posponer más de 6 meses). Acorde a esta clasificación, el grupo de trabajo consensuó la distribución de los diferentes escenarios diagnósticos, terapéuticos y de seguimiento del CP. El riesgo de morbilidad grave como resultado de la infección por SARS-CoV-2puede superar el riesgo de morbi-mortalidad por CP en muchos hombres; por lo tanto, a corto plazo es pocoprobable que los retrasos en el diagnóstico o tratamiento conduzcan a peores resultados oncológicos. CONCLUSIONES: La pandemia COVID-19 ha resultado en un desafío para nuestro sistema de salud, lo que plantea varias consideraciones en el tratamiento de pacientes con CP. La planificación de los procedimientos quirúrgicos en función de los grados de prioridades imprescindible durante el periodo de pandemia y transición a la nueva normalidad. La reorganización de las consultas incluyendo la adaptación a las medidas de seguridad para profesionales y pacientes y el desarrollo de un programa de telemedicina es altamente recomendable.

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.