Totally retroperitoneal approach for robot-assisted nephroureterectomy with bladder cuff without repositioning.

INTRODUCTION: Robot-assisted nephroureterectomy (RANU) for upper urinary tract urothelial carcinoma is typically performed via the transperitoneal approach because of limited surgical space. However, a retroperitoneal approach may be preferable in patients with a history of abdominal surgery or in those in whom pelvic lymph node dissection is unnecessary. MATERIALS AND SURGICAL TECHNIQUES: RANU via the retroperitoneal approach was selected for two patients diagnosed with high-grade upper urothelial carcinoma with a history of abdominal surgery. Nephrectomy was performed in the 90° flank position, and the bed was tilted at 20°. The retroperitoneal space was extended, and the robot trocar was subsequently repositioned in the left lower quadrant. After redocking the robot, the distal ureter was dissected, and the bladder cuff was resected en bloc along with the kidney and the ureter. Neither patient had any complications within 3 months postoperatively. DISCUSSION: By devising a new technique for trocar placement, total retroperitoneal RANU without repositioning was possible, even in a small patient.

Endoscopic intervention versus radical nephroureterectomy for the management of localized upper urinary tract urothelial carcinoma: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: Localized Upper Urinary Tract Urothelial Carcinoma (UTUC) is an uncommon cancer typically detected at an advanced stage. Currently, radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for high-risk UTUC. This meta-analysis aims to evaluate the 5-year overall and cancer-specific survival and bladder recurrence rates in studies comparing endoscopic kidney-sparing surgeries (E-KSS) with RNU in localized UTUC. EVIDENCE ACQUISITION: We performed a literature search on 20th April 2023 through PubMed, Web of Science, and Scopus. The PICOS model was used for study inclusion: P: adult patients with localized UTUC; I: E-KSS. C: RNU; O: primary: overall survival (OS); secondary: cancer-specific survival (CSS), bladder recurrence rate, and metastasis-free survival (MFS). S: retrospective, prospective, and randomized studies. EVIDENCE SYNTHESIS: Overall, 11 studies involving 2284 patients were eligible for this meta-analysis, 737 in the E-KSS group and 1547 in the RNU group. E-KSS showed a similar overall 5-year OS between E-KSS and RNU, and for low-grade tumors, while 5-year OS favored RNU for high-grade tumors (RR 1.84, 95% CI 1.26-2.69, p = 0.002). No difference emerged for 5-year CSS between the two groups, even when the results were stratified for low- and high grade tumors. Bladder recurrence rate and 5-year MFS were also similar between the two groups. CONCLUSIONS: Our review showed that E-KSS is a viable option for patients with localized UTUC with non-inferior oncological outcomes as compared with RNU, except for 5-year OS in high-grade tumors which favoured RNU.

Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients.

BACKGROUND: It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. METHODS: Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. RESULTS: Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). CONCLUSIONS: In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).

Increased risk of bladder cancer recurrence due to bacillus Calmette-Guérin shortage in Brazil.

OBJECTIVE: Our study aimed to evaluate the impact of bacillus Calmette-Guérin shortage on recurrence and progression in patients with non-muscle invasive bladder cancer in a Brazilian cohort. METHODS: We retrospectively reviewed the clinicopathological data of 409 patients who had their first transurethral resection of the bladder tumor for intermediate or high-risk non-muscle invasive bladder cancer between June 2014 and May 2021 in a tertiary public hospital in Brazil. Patients included had non-muscle-invasive urothelial carcinoma of the bladder resected completely for the first time, regardless of bacillus Calmette-Guérin use. Low-risk disease patients were excluded from the analysis. Demographic, clinicopathological, and bacillus Calmette-Guérin use data were collected from our database. Recurrence and progression data were obtained from patient records or through telephone interviews. Recurrence-free survival and progression-free survival were calculated from the date of transurethral resection of the bladder tumor until the events of recurrence, progression, last office visit, or phone interview. RESULTS: Within a median follow-up period of 26.7 months, 168 (41.1%) patients experienced a recurrence in a median time of 27 months (95%CI 16.1-38). Bacillus Calmette-Guérin was administered to 57 (13.9%) individuals after transurethral resection of the bladder tumor. Patients with ≥3 lesions (p<0.001), those with lesions >3 cm (p=0.02), and those without bacillus Calmette-Guérin treatment (p<0.001) had shorter recurrence-free survival. According to a Cox multivariate regression model, bacillus Calmette-Guérin use was independently associated with a reduced recurrence rate, with an HR of 0.43 (95%CI 0.25-0.72). Out of the patients studied, 26 (6.4%) experienced progression. T1 stage (p<0.001) and high-grade (p<0.001) were associated with shorter progression-free survival. Bacillus Calmette-Guérin did not influence bladder cancer progression. In the Cox multivariate analysis, high-risk disease was independently associated with progression (p<0.001). CONCLUSION: Our study confirms that non-muscle invasive bladder cancer exhibits a high recurrence rate. The use of adjuvant bacillus Calmette-Guérin in intermediate and high-risk patients significantly reduces this rate. Furthermore, the bacillus Calmette-Guérin shortage could have negatively impacted these patients.

Adjuvant Chemotherapy and Survival After Radical Cystectomy in Histologic Subtype Bladder Cancer.

OBJECTIVES: Patients with histologic subtype bladder cancer (HSBC) suffer worse outcomes than those with conventional urothelial carcinoma (UC). We sought to characterize the use of adjuvant chemotherapy (AC) in HSBC after radical cystectomy (RC) using the National Cancer Database (NCDB). MATERIALS AND METHODS: We retrospectively queried the NCDB (2006-2019) for patients with non-metastatic bladder cancer (BC) who underwent RC (N = 45,797). Patients were stratified by histologic subtype and receipt of AC. Multivariable logistic regression determined associations of demographic and clinicopathologic features with receipt of AC. Multivariable Cox regression evaluated associations between receipt of any AC and overall survival (OS). RESULTS: We identified 4,469 patients with HSBC classified as squamous, adenocarcinoma, small cell, sarcomatoid, micropapillary, or plasmacytoid. Squamous comprised 31% of the HSBC cohort, followed by small cells and micropapillary. Black patients were presented with a higher prevalence of adenocarcinoma (119/322, 37.0%). Use of AC was highest in plasmacytoid and small cell (30% each) and lowest in squamous (11%). Neuroendocrine histology was independently associated with greater odds of receiving AC (HR 1.6, 95% CI 1.37-1.87), while squamous cell histology was associated with lower odds (HR 0.61, 95% CI 0.53-0.71). On multivariable Cox regression analysis, treatment with AC was associated with significantly longer OS (HR 0.69, 95% CI 0.59-0.81) and for squamous, sarcomatoid, and micropapillary cohorts after stratified by subtype. CONCLUSIONS: AC was variably used among patients with HSBC and was associated with OS benefit in such patients.

Effectiveness of Adjuvant Chemotherapy in Variant Histology Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Stabilized Inverse Probability Treatment Weighting Analysis of Single Center Experience.

PURPOSE: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW). RESULTS: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants. CONCLUSIONS: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors.

Challenges and technical aspects in the management of muscle invasive bladder cancer as retrograde radical cystectomy with ileal conduit.

Objective: To evaluate long-term outcomes in patients homogenously treated with radical cystectomy and ileal conduit for muscle invasive bladder cancer. METHODS: The retrospective study was conducted at the Urology Department of Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data from December 25, 2017, to January 16, 2023, related to patients who underwent radical cystectomy with ileal conduit with or without neo-adjuvant and adjuvant radiation, chemotherapy, or immunotherapy for papillary urothelial carcinom of the bladder. Clinical trajectory, histopathological characteristics and long-term clinical outcomes were noted. Data was analysed using SPSS 20. RESULTS: In our study of 40 patients with muscle invasive bladder cancer, males predominated (32, 80%), with a median age of 57.4 years (IQR: 29-80). Diagnosis was early in 5 (12.5%) patients with varying haematuria durations, while 34 (85%) patients had a smoking history. Comorbidities included hypertension in 17 (42.5%) patients, diabetes in 1 (2.5%) patient, both hypertension and diabetes in 9 (22.5%) patients and a combination of hypertension, diabetes, and ischaemic heart disease in 3 (7.5%) patients. Transurethral resection was performed once in 13 (32.5%) patients and multiple times in 27 (67.5%) patients. Additionally, 5 (12.5%) patients received immunotherapy, 11 (27.5%) patients underwent non-adjuvant radiation, and 14 (35%) patients received non-adjuvant chemotherapy. Papillary urothelial carcinoma was the predominant histological subtype among 37 (92.5%) patients. Patients receiving chemotherapy had significantly better overall survival (p=0.02). No significant differences were noted in recurrence or survival by therapy modality (p>0.05). These findings highlight the significance of early diagnosis, tailored treatments, and comorbidity management in muscle invasive bladder cancer patients. Age stratification revealed significant survival differences across groups (χ²=10.923, df=3, p= 0.012). Analysis by complications did not show age-related survival variations (χ² =3.978, df = 3, p=0.264). Conclusion: Achieving excellent long-term survival in MIBC patients requires a multidisciplinary approach, emphasizing early diagnosis, tailored treatment, and adherence to guidelines and protocols.

The Evolution of Upper Tract Urothelial Carcinoma Management in Kidney Recipients.

INTRODUCTION: Urothelial cancers were one of the most common malignancies in patients with kidney transplants. Although radical nephroureterectomy is still the standard of care in current guidelines, studies have shown that significantly improved perioperative outcomes can be achieved for patients who underwent bilateral nephroureterectomy. Our study provides evidence on the outcome of bilateral nephroureterectomy and unilateral nephroureterectomy in kidney recipients with upper tract urothelial carcinoma. MATERIAL AND METHODS: In the study, the data of patients from a single center, Chang Gung Memorial Hospital Linkou branch, were collected retrospectively from 1981 to 2023. The patient's detailed information was collected through the medical records in the hospital. RESULTS: A total of 44 cases of kidney recipients with upper urinary tract urothelial carcinoma were collected in this study. Of the patients, 19 nephroureterectomies were performed before 2008 and 24 afterward. Incidental findings of contralateral tumors were noted in 3 out of 6 patients who underwent bilateral nephroureterectomy before 2008 and 3 out of 12 after 2008. Contralateral upper urinary tract urothelial carcinoma after unilateral nephroureterectomy was noted in 3 patients within a median of 8.1 years. The progression-free survival of bilateral nephroureterectomy was significantly better compared with a unilateral group (not reached, 15.8 years, respectively). DISCUSSION: Our study, along with previous studies, provides evidence that bilateral nephroureterectomy may be a better treatment option in kidney recipients with upper tract urothelial carcinoma. Our study has several limitations based on its retrospective nature.

Comparison of intravesical chemotherapy regimens after radical nephroureterectomy for upper tract urothelial carcinoma and analysis of risk factors for postoperative recurrence.

OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is a relatively rare but aggressive type of urologic cancer that includes renal pelvic tumors and ureteral tumors with a poor prognosis. Full-length nephroureterectomy plus sleeve bladder resection is the standard treatment for the disease, but patients are prone to recurrence of bladder tumors after surgery. Intravesical infusion therapy is the main means to prevent the recurrence and progression of bladder cancer. Epirubicin and gemcitabine are widely used in clinical practice as first-line or salvage therapy for intravesical chemotherapy; however, the efficacy of these agents is rarely discussed. The purpose of this study was to investigate the effects of epirubicin and gemcitabine on the occurrence of bladder cancer after radical nephroureterectomy for UTUC and to analyze the risk factors affecting the recurrence of postoperative bladder cancer. PATIENTS AND METHODS: A total of 215 patients with diagnosed UTUC and treated in our hospital from June 2019 to August 2021 were retrospectively selected as the research subjects, and they were divided into an observation group (120 cases) and a control group (95 cases) according to different treatment methods. The patients in the control group were treated with epirubicin, while those in the observation group received gemcitabine. All patients were followed up by telephone or outpatient examination for 12 months to record the occurrence of adverse reactions. The occurrence of bladder cancer was recorded at 3 months, 6 months, and 12 months after the surgery. According to the occurrence of bladder cancer after surgery, the patients were divided into a bladder cancer group (63 cases) and a non-bladder cancer group (152 cases). Multivariate Logistic regression analysis was used to analyze the risk factors of bladder cancer after surgery. RESULTS: The total incidence of adverse reactions in the control group was 49.47%, which was higher than that in the observation group with 15.00% (p<0.01). The incidence of bladder tumors in the observation group and the control group was 0.00% and 2.11% at 3 months, 5.00% and 8.42% at 6 months, 13.33% and 15.79% at 12 months, without significant difference (p>0.05). After 12 months of perfusion, the levels of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in the two groups were significantly lower than those before perfusion (p<0.05). In the observation group, the levels of these three factors were slightly decreased compared with those in the control group, without a significant difference (p>0.05). Between the bladder cancer and non-bladder cancer groups, there were significant differences in tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer (p<0.05). The above indexes were all risk factors for postoperative bladder cancer (p<0.05). CONCLUSIONS: Epirubicin and gemcitabine reduced the occurrence of bladder cancer and effectively inhibited tumor angiogenesis after radical nephroureterectomy for UTUC. The tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer were risk factors for postoperative bladder cancer.

Evaluation of histological variants of upper tract urothelial carcinoma as prognostic factor after radical nephroureterectomy.

PURPOSE: To evaluate the impact of variant histology on patients with upper tract urothelial carcinoma (UTUC) survival outcomes. MATERIALS AND METHODS: A total of 519 patients underwent radical nephroureterectomy without neoadjuvant therapy for UTUC at a single institution between May 2003 and December 2019. Multivariate Cox regression analysis evaluated the impact of variant histology on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Among 84 patients (16.2%) with variant histology, the most frequent variant type was squamous cell differentiation (64.3%), followed by glandular differentiation (25.0%) and sarcomatoid variant (2.4%). They showed pathologically advanced T stage (for ≥ T3, 59.5% vs 33.3%, p < 0.001), higher tumor grade (96.4% vs 85.7%, p = 0.025), and higher rates of lymph node metastasis (17.9% vs 7.8%, p = 0.015), angiolymphatic invasion (41.7% vs 25.7%, p = 0.003), tumor necrosis (57.1% vs 29.0%, p < 0.001) and positive surgical margin (13.1% vs 5.7%, p = 0.015). On multivariate Cox regression analyses, variant histology was significantly associated with worse PFS (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.55-3.21; p < 0.001), CSS (HR 2.67; 95% CI 1.35-5.30; p = 0.005) and OS (HR 2.22; 95% CI 1.27-3.88; p = 0.005). In subgroup analysis, no significant survival gains of adjuvant chemotherapy occurred in patients with variant histology. CONCLUSIONS: Variant histology was associated with adverse pathologic features and poor survival outcomes. Our results suggest that patients with variant histology may require a close follow-up schedule and novel adjuvant therapy other than chemotherapy postoperatively.

Open versus minimally invasive nephroureterectomy in octogenarians: An analysis of surgical approach trends, outcomes, and survival analysis with propensity matching.

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) is a rare disease accounting only for 5%-10% of urothelial carcinoma (UC). For localized high-risk disease, radical nephroureterectomy (RNU) is the standard of care. While minimally invasive (MIS) RNU has not been shown to decisively improve overall survival (OS) compared to open surgery, MIS RNU has been associated with reduced hospital length of stay (LOS), blood transfusion requirements and improved recovery, which are important considerations when treating older patients. The purpose of this study is to examine trends in surgical approach selection and outcomes of open vs. MIS RNU in patients aged ≥80 years. METHODS: Using the National Cancer Database (NCDB), patients aged ≥80 years who underwent open or MIS (either robotic or laparoscopic) RNU were identified from 2010 to 2019. Demographic, patient-related, and disease-specific factors associated with either open or MIS RNU were assessed using multivariate logistic regression models. Survival analysis was conducted using Kaplan-Meier plots and Cox-proportional hazard regression. Inverse probability of treatment weighting (IPTW) was utilized to adjust for confounding variables. Survival analysis was also conducted on the IPTW adjusted cohort using Kaplan-Meier plots and Cox-proportional hazard regression. RESULTS: 5,687 patients were identified, with 1,431 (25.2%) and 4,256 (74.8%) patients undergoing open and MIS RNU respectively. The proportion of RNU performed robotically has increased from 12.5% in 2010 to 50.4% in 2019. MIS was associated with a shorter hospital LOS (4.7 days versus 5.9 days, SMD 23.7%). Multivariate analysis revealed that MIS was associated with a significant reduction in 90-day mortality (OR: 0.571; 95%CI: 0.34-0.96, P = 0.033) and improved median OS (53.8 months [95%CI: 50.9-56.9] vs 42.35 months [95%CI: 38.6-46.8], P < 0.001) compared to open surgery. IPTW-adjusted survival analysis revealed improved median OS with MIS when compared to open surgery, with a survival benefit of 46.1 months (95%CI: 40.2-52.4 months) versus 37.7 months (95%CI: 32.6-46.5 months, P = 0.0034) respectively. IPTW-adjusted cox proportional hazard analysis demonstrated that MIS was significantly associated with reduced mortality (HR 0.76, 95%CI: 0.66-0.87, P < 0.001). CONCLUSION: In octogenarians undergoing RNU, MIS is associated with improved median OS and 90-day mortality.

Cardiac and Intramuscular Metastases Following Nephroureterectomy for Metachronous Urothelial Carcinoma.

BACKGROUND We present a case of metachronous cardiac and intramuscular metastases in a patient with a known history of radical nephroureterectomy for upper-tract urothelial carcinoma (UTUC). CASE REPORT A 58-year-old man had a history of metachronous renal pelvis urothelial carcinoma with prior left radical nephroureterectomy. He was also diagnosed with malignancy-associated deep vein thrombosis (DVT) and was on rivaroxaban. He presented at an oncology follow-up consult with shortness of breath and right scapular lump. CT scan revealed a soft-tissue mass at the surgical bed suspicious for local recurrence, as well as intracardiac hypodensities and intramuscular nodules in the right latissimus dorsi and right adductor muscles. The intracardiac hypodensities were located in the left atrial appendage and inter-atrial septum. Given that the patient had a history of DVT and in a pro-thrombotic state, differentials for the intracardiac densities included intracardiac thrombi or metastases. The intramuscular hypodensities were rim-enhancing. Given that the patient was on rivaroxaban, differentials included hematomas or metastases. As there was no overlying bruising and the lesions remained unchanged in size clinically, they were treated as metastases. The patient was treated with clexane but re-presented with worsening of shortness of breath and palpitations. CT scan showed increased size of intracardiac lesions, suggesting no response to anticoagulation, and therefore were likely metastatic in nature. He completed a 2-year course of IV pembrolizumab and was in complete remission. CONCLUSIONS Our case highlights the importance of this clinically challenging scenario when patients with known malignancy and on anticoagulation present with cardiac or musculoskeletal symptoms. Though these patients are at risk of thrombus and haematoma, cardiac and intramuscular metastasis should be considered, as the prognosis is guarded.

Impact of Preoperative Plasma Potassium Levels on Oncological Outcomes, Major Complications, and 30-Day Mortality in Bladder Cancer Patients Undergoing Radical Cystectomy.

INTRODUCTION AND OBJECTIVES: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. PATIENTS AND METHODS: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. RESULTS: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05). CONCLUSION: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.