Robot-assisted nephroureterectomy: surgical and mid-term oncological outcomes in over 1100 patients (ROBUUST 2.0 collaborative group).

OBJECTIVE: To analyse surgical, functional, and mid-term oncological outcomes of robot-assisted nephroureterectomy (RANU) in a contemporary large multi-institutional setting. PATIENTS AND METHODS: Data were retrieved from the ROBotic surgery for Upper tract Urothelial cancer STtudy (ROBUUST) 2.0 database, an international, multicentre registry encompassing data of patients with upper urinary tract urothelial carcinoma undergoing curative surgery between 2015 and 2022. The analysis included all consecutive patients undergoing RANU except those with missing data in predictors. Detailed surgical, pathological, and postoperative functional data were recorded and analysed. Oncological time-to-event outcomes were: recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, with a 3-year cut-off. A multivariable Cox proportional hazard model was built to evaluate predictors of each oncological outcome. RESULTS: A total of 1118 patients underwent RANU during the study period. The postoperative complications rate was 14.1%; the positive surgical margin rate was 4.7%. A postoperative median (interquartile range) estimated glomerular filtration rate decrease of -13.1 (-27.5 to 0) mL/min/1.73 m2 from baseline was observed. The 3-year RFS was 59% and the 3-year MFS was 76%, with a 3-year OS and CSS of 76% and 88%, respectively. Significant predictors of worse oncological outcomes were bladder-cuff excision, high-grade tumour, pathological T stage ≥3, and nodal involvement. CONCLUSIONS: The present study contributes to the growing body of evidence supporting the increasing adoption of RANU. The procedure consistently offers low surgical morbidity and can provide favourable mid-term oncological outcomes, mirroring those of open NU, even in non-organ-confined disease.

Beyond the knife: strategic patient selection for cytoreductive nephrectomy.

PURPOSE OF REVIEW: To evaluate the current role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) within the context of evolving treatment paradigms, focusing on implications for patient selection. RECENT FINDINGS: Two randomized trials failed to show significant benefits from CN for intermediate and poor-risk patients undergoing targeted therapy. Despite this, subgroup analysis and retrospective data suggest potential benefits for a subset of good and intermediate-risk patients. Although currently used risk stratification tools guide CN eligibility, they have limitations, including, subjectivity, perioperative variability, and missing validation. Deferred CN may benefit patients responding to systemic treatment, whereas other patients may benefit from upfront CN. Emerging data supports the value of CN with immune checkpoint inhibitors (ICI) in selected patients, emphasizing the need for ongoing trials in the ICI era. SUMMARY: The role and timing of CN in mRCC have evolved across therapeutic eras. Although awaiting prospective evidence in the current era of ICI, CN still has a role in the therapeutic approach for a subset of patients. The decision to recommend CN must be personalized and involve multidisciplinary discussions considering both patient- and tumor-related factors.

Treatment of adrenocortical carcinoma: oncological and endocrine outcomes.

PURPOSE OF REVIEW: Adrenocortical carcinoma (ACC) is a rare, aggressive disease with a paucity of data and great variability between published studies regarding its treatment. This review provides information on current clinical management and oncological and endocrine outcomes. RECENT FINDINGS: Complete surgical resection is the only potentially curative treatment for adrenocortical carcinoma (ACC). Adjuvant mitotane treatment is recommended in patients with favourable/intermediate prognosis. As part of the endocrine follow-up, steroid hormones and thyroid hormones may be decreased or increased and may need to be substituted or suppressed. Recurrences are common. If the disease-free interval is more than 12 months, surgery is a treatment if complete resection is feasible. In advanced/metastatic ACC patients, the prognosis is poor. Mitotane monotherapy is only appropriate for patients with low tumour burden and indolent disease. Patients with unfavourable prognosis should be treated with aggressive cytotoxic therapy. Patients requiring third-line treatment should be considered for clinical trials. Immunotherapy and targeted therapy are currently being investigated, but have so far yielded only unsatisfactory results. SUMMARY: There is scarce evidence for the treatment of ACC, which often complicates clinical decision-making. Patients who progress on EDP-M should be treated in clinical trials.

Poly(ADP-ribose) polymerase inhibitors in prostate and urothelial cancer.

PURPOSE OF REVIEW: The aim of this article is to give an overview of poly(ADP-ribose) polymerase inhibitors (PARPis) trials in prostate cancer and to discuss emerging approaches with potential future clinical implementation in both prostate and urothelial cancer. RECENT FINDINGS: PARPis are a class of drugs that can be applied for the treatment of homologous recombination repair (HRR)-deficient tumors. Tumors are potentially sensitive to PARPi harbor mutations in genes relevant for DNA damage repair, such as BRCA1/2 or ATM, which are present to a significant degree in metastatic prostate and urothelial cancer patients. Several PARPis have been successfully tested in clinical trials for HRR-deficient metastatic castration-resistant prostate cancer (mCRPC), and olaparib and rucaparib have recently received breakthrough approval in BRCA1/2 mutated mCRPC. Combination treatment of PARPis with androgen-receptor inhibitors or with checkpoint inhibitors and earlier frontline applications are currently being evaluated, and clinical trials enrolling bladder cancer (BCa) patients with HRR deficiency have recently been initiated. SUMMARY: Approximately 10% of mCRPC patients and 34% of metastatic BCa patients have tumors with HRR deficiency and may benefit from PARPi treatment. Correct identification of these patients as well as determining the most adequate time point for drug administration will be key to successful clinical implementation.

An up-to-date catalogue of urinary markers for the management of prostate cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Poor specificity and sensitivity of total PSA often results in over and sometimes underdetection/treatment. Therefore, more specific and sensitive biomarkers for the detection and monitoring especially of clinically significant PCa as well as treatment-specific markers are much sought after. In this field, urine has emerged as a promising noninvasive source of biomarkers. RECENT FINDINGS: RNA-based biomarkers are the most extensively studied type of urinary nucleic acids. ERG-Score/MiPS (Mi-Prostate Score) and SelectMDx might be considered as additional parameters together with clinical and imaging modalities to decrease unnecessary biopsies. miR Sentinel Tests could make it possible to accurately detect the presence of cancer and to distinguish low-grade from high-grade disease. In men with previous negative biopsies, PCA3 may suggest the need to repeat biopsy. SUMMARY: The definitive role of these markers and their clinical benefit needs future validation.

Secretion of severe acute respiratory syndrome coronavirus 2 in urine.

PURPOSE OF REVIEW: Despite the plethora of publications discussing the severe respiratory coronavirus 2 (SARS-CoV-2), evidence of viral secretion in urine is sparse. RECENT FINDINGS: We could identify 34 publications including a total of 2172 patients. Among those, 549 patients were tested for SARS-CoV-2 secretion in urine, which was detected in only 38 patients (6.9%). Within the seven studies displaying positive results, the majority of positive patients (86.8%) was from not yet peer-reviewed studies including weak data and heterogeneous techniques for sample testing. Furthermore, none of the studies available in the literature addressed the virulence of detected viral RNA in urine. SUMMARY: Overall, only seven studies were able to detect SARS-CoV-2 secretion in urine, all of them with a considerably low rate of positivity. However, these studies were of rather low quality considering their methodology. Despite this, as SARS-CoV-2 has been detected in urine, it is of importance to discuss safety and urinary hygiene protocols. Until further research provides valid data on viral shedding and virulence in urine, potential risk of transmission through urine cannot be ruled out. Therefore, safety and hygiene measures need to be discussed.

Adjuvant Therapy in Stage I Testicular Cancer: Surveillance for All.

Given the remarkably high cure rates for clinical stage (CS) I testicular cancer, the toxicities and risks of adjuvant treatments, the cost effectiveness of surveillance, and the lack of reliable biomarkers to predict relapse, surveillance should be recommended for all patients with CS I testicular cancer.

Evidence and emerging trends in local therapy for metastatic hormone-sensitive prostate cancer: a narrative review.

Introduction: Metastatic hormone-sensitive prostate cancer (mHSPC) displays both simultaneous and sequential patterns of metastasis, emphasizing a comprehensive treatment approach that integrates both local therapy and systemic treatment strategies. The increasing use of molecular imaging has led to a rise in mHSPC diagnoses, underscoring the importance of identifying the right patient population and effective treatment concepts for this disease state. Results: Two prospective trials, HORRAD and STAMP EDE, investigated prostate radiotherapy (RT) for mHSPC; however, they did not show an overall survival (OS) benefit in the unselected cohort. Nonetheless, RT showed favorable outcomes in patients with fewer than five bone metastases, resulting in a 7% 3-year survival improvement and supporting the integration of RT in multimodal treatment for men with oligometastatic mHSPC. Regarding cytoreductive prostatectomy (cRP), the TRoMbone Trial confirmed its feasibility and safety. In addition, findings from the FUSCC-OMPCa Trial demonstrated improved 3-year radiographic progression-free survival and OS rates with acceptable rates of complications and incontinence. Recent data from the LoMP registry have further supported superior OS and cancer-specific survival (CSS) in patients undergoing cRP compared to systemic therapy alone. Notably, no significant differences in OS and CSS were observed between the cRP and RT groups. However, cRP-treated patients exhibited superior 2-year local event-free survival when compared to those treated with RT. Conclusion: RT in combination with systemic therapy remains the established first-line treatment for low-burden mHSPC, though the exact definition of low metastatic burden remains contentious. Precise assessment of metastatic burden is vital to identify patients who would derive the greatest benefit from RT. As treatment paradigms evolve, embracing multimodal approaches holds potential for optimizing outcomes in patients with mHSPC. Further research is needed to solidify the role of cRP as a standard therapeutic approach and to refine treatment strategies for improved patient outcomes.

Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

The impact of bladder cuff excision on outcomes after nephroureterectomy for upper tract urothelial carcinoma: An analysis of the ROBUUST 2.0 registry.

OBJECTIVES: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS AND MATERIALS: A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups. RESULTS: Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision. CONCLUSIONS: Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear.