Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Current role of intraoperative cell salvage techniques in the management of renal tumors with level III and IV inferior vena cava thrombus extension.

Background: En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for renal cell carcinoma (RCC) with tumor thrombus extension. In order to minimize the hemodynamic impact of the surgical blood loss, intraoperative cell salvage (IOCS) techniques can decrease the need for allogeneic blood and prevent blood transfusion related complications. Objective: In this article, we evaluated the safety of IOCS during radical nephrectomy with inferior vena cava thrombectomy under cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Design and method: In this retrospective comparative multicenter analysis, clinical characteristics of 27 consecutive patients who underwent surgery with or without IOCS between 2012 and 2022 in three referral care units were collected into a database. The need for an allogenic blood transfusion (ABT) was also recorded, defined as any transfusion that occurred either intraoperatively or during the hospital stay. Results: The need for ABT in the cell saver arm was significantly smaller due to the reinfusion of rescued blood (p < 0.015). In multivariate analysis, no cell saver usage was an independent predictor for complications ⩾3 Clavien 3a [odds ratio (OR) 18.71, 95% CI 1.056-331.703, p = 0.046]. No usage of IOCS was an independent predictor for a lower risk of death (OR 0.277, 95% CI 0.062-0.825, p = 0.024). During follow-up, patients who received salvaged blood did not experience an increased risk for developing local recurrence or distant metastases. Conclusion: Transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced RCC.

Role of intraoperative cell salvage techniques in the management of renal tumors with advanced caval extension En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for RCC with tumor thrombus extension. Intraoperative cell salvage techniques (IOCS) can decrease the need for allogeneic blood and prevent blood transfusion related complications. In this article we demonstrated that transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced renal cell carcinoma.

How to Integrate Prostate Cancer Biomarkers in Urology Clinical Practice: An Update.

Nowadays, the management of prostate cancer has become more and more challenging due to the increasing number of available treatment options, therapeutic agents, and our understanding of its carcinogenesis and disease progression. Moreover, currently available risk stratification systems used to facilitate clinical decision-making have limitations, particularly in providing a personalized and patient-centered management strategy. Although prognosis and prostate cancer-specific survival have improved in recent years, the heterogenous behavior of the disease among patients included in the same risk prognostic group negatively impacts not only our clinical decision-making but also oncological outcomes, irrespective of the treatment strategy. Several biomarkers, along with available tests, have been developed to help clinicians in difficult decision-making scenarios and guide management strategies. In this review article, we focus on the scientific evidence that supports the clinical use of several biomarkers considered by professional urological societies (and included in uro-oncological guidelines) in the diagnosis process and specific difficult management strategies for clinically localized or advanced prostate cancer.

Triple therapy in metastatic hormone-sensitive prostate cancer.

PURPOSE OF REVIEW: Over the last years, there have been striking changes in the management of metastatic hormone-sensitive prostate cancer (mHSPC) based on survival advantage of combining either a new hormonal agent (NHA) or docetaxel (D) with androgen deprivation therapy (ADT). Some of these studies primarily assessing doublet treatment included men who underwent concomitant or sequential treatment with D. Most recently, prospective randomized evidence emerged on this triplet strategy too. We aimed to outline the current data and ongoing trials evaluating the usage of the triplet therapy in male individuals with mHSPC. RECENT FINDINGS: Phase III trials PEACE-1 and ARASENS showed that the upfront triplet treatment with ADT+D and either abiraterone acetate or darolutamide outperformed ADT+D in terms of survival, while severe toxicity was mainly driven by D. Importantly, prospective evidence comparing triplet vs. ADT+NHA is still lacking. SUMMARY: Men with de novo high-volume disease benefit most from the triplet, while in cases with metachronous and/or low-volume disease, survival advantage is still disputable. As efficacy of ADT+NHA does not appear to be substantially amplified by combination with D, those men with a more favorable underlying tumor biology might mostly benefit from this doublet, also taking quality-adjusted survival into account.

Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives.

PURPOSE: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.

Challenges in Diagnosis of Uretero-Arterial Fistulas after Complex Pelvic Oncological Procedures-Single Center Experience and Review of the Literature.

Introduction: Uretero-arterial fistula (UAF) represents a rare condition that manifests as massive or intermittent hematuria and requires collaboration between a urologist, vascular surgeon and interventional radiologist. In this article, we present our experience with UAF diagnosis, treatment pathways and the results of a nonsystematic review of the literature published in the last decade regarding modern diagnostic procedures. Material and method: We analyzed the clinical data of nine consecutive patients from our institution diagnosed with UAF in the interval of 2012-2022 who underwent open or endovascular surgical treatment. We reviewed patient characteristics, diagnoses and treatment pathways. The literature search resulted in 14 case series, published from 2012 to 2022, describing a total of 670 cases of UAF. Results: The mean age of patients in our cohort was 65.3 years (IQR: 51-79). UAFs were more common in women (77.7%). All patients presented a history of surgical intervention and ir-radiation for pelvic malignancy with permanent ureteric stenting. Overall, 88.8% of patients had urinary diversion, either via ileal conduit or cutaneous ureterostomy. The most common clinical manifestation of UAF was gross hematuria with or without clots accompanied by flank pain due to stent obstruction, while three patients presented with hypovolemic shock. Angiography represents the best option for diagnosis, followed by angioCT, with a sensitivity of 59.83% and 47.01%, respectively. There is no definitive imaging modality associated with high accuracy in detecting UAF and negative findings do not exclude the disease. In emergency cases with massive bleeding, surgical exploration remains the most appropriate management option for both diagnosis and treatment. Endovascular stent graft placement is preferred over open surgery in stable hemodynamic patients. Conclusions: Uretero-arterial fistulas represent a life-threatening complication and must be treated with great awareness. Angiography represents the best modality for diagnosis, followed by computed tomography. However, there is no definitive imaging modality and, in some cases, open approach remains the only option for diagnosis and treatment.

Molecular Mechanisms Related with Oligometastatic Prostate Cancer-Is It Just a Matter of Numbers?

During the last decade, the body of knowledge regarding the oligometastatic state has increased exponentially. Several molecular frameworks have been established, aiding our understanding of metastatic spread caused by genetically unstable cells that adapt to a tissue environment which is distant from the primary tumor. In the current narrative review, we provide an overview of the current treatment landscape of oligometastatic cancer, focusing on the current biomarkers used in the identification of true oligometastatic disease and highlighting the impact of molecular imaging on stage shift in different scenarios. Finally, we address current and future directions regarding the use of genetic and epigenetic targeting treatments in oligometastatic prostate cancer.

Multicentric comparative analysis of Retzius versus Retzius sparing robotic assisted simple prostatectomy in the management of large prostate glands.

AIM: Robot-assisted simple prostatectomy (RASP) is a minimally invasive alternative to open simple prostatectomy in the management of patients with large prostate glands suffering from moderate-to-severe lower urinary tract symptoms (LUTS). Our study aimed to evaluate two transvesical robotic approaches in order to compare functional outcomes and postoperative complications. MATERIALS AND METHODS: Clinical data from 111 consecutive patients from three tertiary robotic centers were retrospectively collected. Patients were divided into two groups depending on the surgical approach: 58 Retzius sparing and 53 Retzius approach RASP. We evaluated peri-operative outcomes (operating time, blood loss, transfusion rate, length of hospital stay), as well as intra-operative and early complications using a Clavien Dindo scale. Fisher's exact test, chi-square test and Mann-Whitney U test were applied for statistical analyses. A p-value <0.05 was considered statistically significant. RESULTS: Neither subgroup differed significantly in age (p = 0.104), Charlson comorbidity index (p = 0.088) or prostate volume (p = 0.507), total IPSS score (0.763) and Qmax (p = 0.651). Total complication rates were lower for the Retzius approach subgroup (19 vs 11.9%) without reaching statistical significance in multivariate analysis (HR = 1.21, 95% CI = 0.17 - 8.44, p = 0.84). No significant differences based on IPSS total score and Qmax could be observed between the two subgroups during follow-up. CONCLUSIONS: Both RASP approaches provide similar results in terms of functional outcomes and present a good safety profile in the management of large prostatic adenomas. Larger trials are needed in order to establish the indications for each robotic technique.

Recent Insights on Genetic Testing in Primary Prostate Cancer.

Prostate cancer (PCa) is one of the most common cancers in developed countries. The results of large trials indicate that the proportion of PCa attributable to hereditary factors is as high as 15%, highlighting the importance of genetic testing. Despite improved understanding of the prevalence of pathogenic variants among men with PCa, it remains unclear which men will most benefit from genetic testing. In this review, we summarize recent evidence on genetic testing in primary PCa and its impact on routine clinical practice. We outline current guideline recommendations on genetic testing, most importantly, for mutations in BRCA1/2, MMR, CHEK2, PALB2, and HOXB13 genes, as well as various single nucleotide polymorphisms associated with an increased risk of developing PCa. The implementation of genetic testing in clinical practice, especially in young patients with aggressive tumors or those with positive family history, represents a new challenge for the coming years and will identify men with pathogenic variants who may benefit from early screening/intervention and specific therapeutic options.

Health-related Quality of Life in Patients with Advanced Prostate Cancer: A Systematic Review.

CONTEXT: The assessment of "soft" endpoints such as health-related quality of life (HRQOL) is increasingly relevant when evaluating the optimal treatment sequence of novel therapeutic options in patients with advanced prostate cancer (PCa). OBJECTIVE: To systematically review contemporary data regarding HRQOL outcomes in patients with advanced PCa. EVIDENCE ACQUISITION: A systematic review of the literature published between January 2011 and March 2019 was performed using the PubMed/Medline Database. In total, 873 articles were screened, and 14 articles including 12 661 patients were selected for synthesis and included in the current analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and European Association of Urology recommendations. EVIDENCE SYNTHESIS: Regarding HRQOL assessment, the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire was used in 11 of 14 studies, the European Quality of Life 5-Dimensions (EQ-5D) questionnaire in six of 14 studies, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) in two of 14, and its prostate-specific amendment QLQ-PR25 was used in one of 14 studies. Three studies included patients with metastatic castration-sensitive prostate PCa, and found beneficial HRQOL effects for abiraterone acetate and docetaxel compared with standard androgen deprivation therapy. Two studies included patients with nonmetastatic castration-resistant PCa, and positive HRQOL effects for enzalutamide and apalutamide were observed. Nine studies focused on patients with metastatic castration-resistant PCa. Hereby, beneficial HRQOL outcomes were described for enzalutamide, abiraterone acetate, and radium-223. Evidence synthesis was mostly based on studies with a low risk of bias based on standardized risk of bias assessment. Limitations include hampered comparability between different validated questionnaires, lack of baseline values, and unclear impact of supportive care on HRQOL outcomes. CONCLUSIONS: There is strong evidence from several phase III trials supporting a beneficial effect of current systemic treatment options on HRQOL outcomes in patients with advanced PCa compared with standard androgen deprivation therapy. PATIENT SUMMARY: In this systematic review, we provide an overview of contemporary data from large clinical trials on the effect of current treatment strategies on patients' health-related quality of life (HRQOL). We summarize the assessment tools that have been used to measure HRQOL and show that there are robust data for positive HRQOL effects of numerous agents in different clinical stages of advanced prostate cancer.

External Validation of the 2019 Briganti Nomogram for the Identification of Prostate Cancer Patients Who Should Be Considered for an Extended Pelvic Lymph Node Dissection.

The 2019 Briganti nomogram was developed to calculate the risk of lymph node invasion (LNI) and identify prostate cancer (PCa) patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy who should be considered for an extended pelvic lymph node dissection (ePLND). Since its implementation is still limited by lack of a formal external validation, we aimed to validate this tool in a large contemporary cohort. We identified 487 patients diagnosed using MRI-targeted with concomitant systematic biopsy who underwent radical prostatectomy (RP) and an anatomically defined ePLND at six centers. The external validity of the 2019 Briganti nomogram for estimating LNI risk was assessed via calibration, discrimination, and decision curve analyses (DCAs). A total of 38 (8%) patients had LNI at final pathology. The median number of nodes removed was 18 (interquartile range 14-24). On external validation, the 2019 Briganti nomogram had an area under the receiver operating characteristic curve (AUC) of 79%. Although there was some miscalibration, this was at predicted probabilities >35% and therefore outside the clinically relevant range. DCA demonstrated that the 2019 Briganti nomogram improved clinical risk prediction against LNI threshold probabilities of ≤30%. For a 7% cutoff, 273 (56%) ePLNDs would be spared and only 2.6% LNIs would be missed. The 2019 Briganti nomogram was characterized by higher AUC compared to the 2012 and 2017 Briganti nomograms and the Memorial Sloan Kettering Cancer Center risk calculator (79% vs 75% vs 65% vs 74%) and demonstrated the highest net benefit on DCA. This first multi-institutional validation of the 2019 Briganti nomogram in predicting LNI in PCa patients diagnosed with MRI-targeted biopsy confirms the highest AUC, better calibration and the highest net benefit compared with available tools and should be adopted to identify candidates for ePLND among men diagnosed with MRI-targeted biopsy. PATIENT SUMMARY: We performed the first multi-institutional validation of the first nomogram predicting lymph node invasion specifically developed using data from prostate cancer patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. This nomogram exhibited excellent characteristics on external validation compared with available tools and should be adopted to identify candidates for extended pelvic lymph node dissection among men diagnosed with MRI-targeted biopsy.

External validation of a postoperative nomogram for the prediction of disease-specific survival in patients with papillary renal cell carcinoma using a large multicenter database.

PURPOSE: Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC). METHODS: A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied. RESULTS: The median follow-up was 38 months (IQR 11.8-80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60-0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77-0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20-80), but the median actual 5-year DSS in the same group was 58% (95% CI 52-65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%. CONCLUSIONS: The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.

Surgical management of urachal tumors: Can the umbilicus be sparred in localized disease?

Urachal adenocarcinoma represents the third most common histological type of non-urotelial bladder cancer. A very low incidence of this disease and the lack of prospective studies have led to a rich and heterogeneous treatment history. Currently, the standard of care for these patients is represented by partial cystectomy en bloc with resection of the urachal ligament and total omphalectomy. The aim of this article is to present our experience and results in the management of patients with urachal adenocarcinoma. Between 2005 and 2015, 16 patients have undergone surgical treatment for urachal adenocarcinoma in "Fundeni" Clinical Institute and Madrid University Hospital "Infanta Sofia." Partial cystectomy was performed in 11 (68.76%) patients, while radical cystectomy en bloc with omphalectomy was performed in 5 (31.25%) patients, which were not amendable to a limited resection. The Sheldon classification was used, as it provides appropriate disease staging and is the most commonly utilized. Postoperative pathological results showed that 7 (43.75%) patients had localized tumors, and more than one-third (37.5%) of the patients had locally advanced Sheldon III disease, while 3 patients had distant metastasis at the time of surgery. Lymph node involvement was present in 3 patients (18.75%). Mean follow-up time was 2.5 years, ranging from 4 months to 7.6 years. Three patients (18.75%) were lost to follow-up, without any documented signs of local or systemic recurrence and were cancer free at the time of the last evaluation. In cases with lymph node involvement, local recurrence or distant metastasis, patients underwent cisplatin- or 5-fluorouracil-based salvage chemotherapy. Surgical treatment represents the gold standard, while adjuvant chemotherapy has a limited impact on overall survival. The utility of navel resection is questionable due to the rarity of direct invasion or local recurrence.

Aggressive variants of prostate cancer - Are we ready to apply specific treatment right now?

Recently, adoption of novel drugs for systemic treatment of metastatic prostate cancer has led to a striking improvement of response rate and survival in both hormone-sensitive and castration-resistant disease. In most cases, prostate cancer essentially depends on androgen receptor signaling axis, even in castration-resistant setting, and hence may be targeted by second generation hormonal therapy. However, a subset of patients bears androgen-independent cancer biology with a short-term response to hormonal treatment, early and extensive visceral metastases, low PSA levels and poor outcomes. Identification and specific management of these rapidly fatal malignancies is of an unmet medical need since their classification and utilized therapeutic regimens vary significantly. Unfortunately, molecular pathways have not been sufficiently elucidated yet in order to provide an effective targeted treatment with a prolonged response. Lack of diagnostic and predictive biomarkers for these cancers makes successful counteractions against them even more sophisticated. In this comprehensive review, we aimed at summarizing the current body of literature reporting on causal molecular machinery as well as diagnostic and therapeutic concepts of aggressive prostate tumors and draw clinically relevant conclusions for the up-to-date sensible disease management.

Adjuvant recMAGE-A3 Immunotherapy After Cystectomy for Muscle-invasive Bladder Cancer: Lessons Learned from the Phase 2 MAGNOLIA Clinical Trial.

The MAGNOLIA study, investigating the concept of perioperative immunotherapy in muscle- invasive bladder cancer, was prematurely terminated. The lessons learned that should be considered before initiating and conducting future clinical trials in this field are highlighted.

Positive pre-biopsy MRI: are systematic biopsies still useful in addition to targeted biopsies?

PURPOSE: The diagnostic strategy implementing multiparametric magnet resonance tomography (mpMRI) and targeted biopsies (TB) improves the detection and characterization of significant prostate cancer (PCa). We aimed to assess the clinical usefulness of systematic biopsies (SB) in the setting of patients having a pre-biopsy positive MRI. METHODS: A review of the literature was performed in March 2018. All studies investigating the performance of SB in addition to TB (all techniques) were assessed, both in the biopsy-naïve and repeat biopsy setting. RESULTS: Evidence demonstrates that TB improves the detection of index-significant PCa compared with SB alone, in both initial and repeat biopsy settings. However, the combination of both TB and SB improved the overall (around 30%) and significant (around 10%) PCa detection rates as compared with TB alone. Significant differences between both biopsy approaches exist regarding cancer location favoring SB for the far lateral sampling, and TB for the anterior zone. Main current pitfalls of pure TB strategy are the learning curve and experience required for mpMRI reading and biopsy targeting, as well as the precision assessment in TB techniques. CONCLUSION: A pure TB strategy omitting SB leads to the risk of missing up to 15% of significant cancer, due to limitations of mpMRI performance/reading and of precision during lesion targeting. SB remain necessary, in addition to the TB, to obtain the most accurate assessment of the entire prostate gland in this sub-group of patients at risk of significant disease.

Imaging modalities in synchronous oligometastatic prostate cancer.

PURPOSE: Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. METHODS: A literature search on December 15th 2017 was conducted using the Pubmed database. RESULTS: Functional imaging techniques like 68Ga PSMA. 68Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. CONCLUSIONS: Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.

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

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

Combining anticancer drugs with osteoprotective agents in prostate cancer-A contemporary update.

Recently, a plethora of life-prolonging cytotoxic, next-generation hormonal, immunotherapeutical as well as radionuclide therapies has emerged as a standard care for metastasized castration-resistant prostate cancer. Being strikingly effective in cancer control, these novel therapies might in fact exert a beneficial impact on skeletal events. Therefore, combining anticancer drugs with osteoprotective agents might lead to additional clinical advantage but must be weighed against simultaneously exposing patients to serious toxicities. In addition, further survival prolongation by changing treatment paradigm in both metastasized hormone-sensitive and nonmetastatic castration-resistant disease might potentially increase the risk for bone density reduction complications due to a growing efficacy of androgen ablation leading to prolonged exposure. To address both possible indications of combined treatment and to draw practical conclusions, we performed a comprehensive review of the currently available evidence.

Prognostic and discriminative power of the 7th TNM classification for patients with surgically treated papillary renal cell carcinoma: results of a multi-institutional validation study (CORONA subtype project).

OBJECTIVE: Studies on the prognostic reliability of the Union for International Cancer Control tumor, node, metastasis (TNM) staging system for renal cell carcinoma (RCC) predominantly focus on clear-cell RCC. Therefore, the aim of this study was to investigate whether the oncological prognosis of surgically treated papillary RCC (papRCC) patients is reliably given by the current TNM system, by analyzing the largest database reported to date. MATERIALS AND METHODS: Data on 2325 papRCC patients who underwent surgical treatment in 1984- 2015 were collated from 17 international centers (median follow-up 47 months). Tumor stage was adapted to the 7th edition of the TNM system. Multivariable, bootstrap-corrected Cox regression models were applied to assess the independent impact of the TNM system on cancer-specific mortality (CSM) and all-cause mortality (ACM). RESULTS: The median age at diagnosis was 63 years (interquartile range 54-70 years) and 77% of patients were male. Nephron-sparing surgery was performed in 42%, and 82% were with symptom free at diagnosis. In 6.7% (n = 156), organ metastasis (stage M1) was present at the time of surgery. On multivariable analysis, the TNM system and Fuhrman grade had an independent impact on both CSM and ACM, while patient age affected ACM only. The discriminative ability of the pT classification was significant for both endpoints: 5 year CSM rates were 5%, 17%, 36% and 56% for stages pT1, pT2, pT3 and pT4, respectively (each p < 0.001). The pT classification contributed significantly to the predictive accuracy of the CSM and ACM models by 6.3% and 2.5%, respectively (each p < 0.001). CONCLUSIONS: The 2010 TNM staging system can be reliably applied to papRCC patients and allows certain prognostic discrimination.