Effect of positive surgical margins at radical prostatectomy on cancer-specific mortality in high/very high-risk prostate cancer patients with Gleason Grade Group 4-5.

BACKGROUND: The effect of positive surgical margins (PSM) on cancer specific mortality (CSM) in high/very high-risk (HR/VHR) prostate cancer (PCa) with aggressive Gleason Grade Group (GGG) is unknown. We tested PSM effect on CSM in this setting, in addition to testing of radiotherapy (RT) benefit in PSM patients. METHODS: We relied on Surveillance, Epidemiology, and End Results database (2010-2015), focusing on HR/VHR patients with exclusive GGG 4-5 at radical prostatectomy (RP). Kaplan-Meier plots and multivariable Cox regression models tested the relationship between PSM and CSM. Moreover, the effect of RT on CSM was explored in PSM patients. RESULTS: Of 3383 HR/VHR patients, 15.1% (n = 511) exhibited PSM. Patients with PSM harbored higher rates of GGG 5 (60.1% vs. 50.9%, p < 0.001), pathologic tumor stage T3a (69.1% vs. 45.2%, p < 0.001) and lymph node involvement (14.1% vs. 9.4%, p < 0.001), relative to patients without PSM. PSM rates decreased over time (2010-2015) from 16.0% to 13.6%. Seven-year CSM-free survival rates were 91.6% versus 95.7% in patients with and without PSM, respectively. In multivariable Cox regression models, PSM was an independent predictor of CSM (hazard ratio = 1.6, p = 0.040) even after adjustment for age, prostate specific antigen, pathologic tumor stage and lymph node status. Finally, in PSM patients, RT delivery did not reduce CSM in either univariable or multivariable Cox regression models. CONCLUSIONS: In HR/VHR PCa patients with exclusive GGG 4-5, PSM at RP adversely affect survival. Moreover, RT has no protective effect on CSM. In consequence, lowest possible PSM rates are crucial in such patients.

The association of type and number of high-risk criteria with cancer specific mortality in prostate cancer patients treated with radiotherapy.

BACKGROUND: To assess the association between of type and number of D'Amico high-risk criteria (DHRCs) with rates of cancer-specific mortality (CSM) in prostate cancer (PCa) patients treated with external beam radiotherapy (RT). METHODS: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 34,908 RT patients with at least one DHRCs, namely prostate-specific antigen (PSA) >20 ng/dL (hrPSA), biopsy Grade Group (hrGG) 4-5, clinical T stage (hrcT) ≥T2c. Multivariable Cox regression models (CRM), as well as competing risks regression (CRR) model, which further adjust for other cause mortality, tested the association between DHRCs and 5-year CSM. RESULTS: Of 34,908 patients, 14,777 (42%) exclusively harbored hrGG, 5641 (16%) hrPSA, 4390 (13%) had hrcT. Only 8238 (23.7%) harbored any combination of two DHRCs and 1862 (5.3%) had all three DHRCs. Five-year CSM rates ranged from 2.4% to 5.0% when any individual DHRC was present (hrcT, hrPSA, hrGG, in that order), versus 5.2% to 10.5% when two DHRCs were present (hrPSA+hrcT, hrcT+hrGG, hrPSA+hrGG, in that order) versus 14.4% when all three DHRCs were identified. In multivariable CRM hazard ratios relative to hrcT ranged from 1.07 to 1.76 for one DHRC, 2.20 to 3.83 for combinations of two DHRCs, and 5.11 for all three DHRCs. Multivariable CRR yielded to virtually the same results. CONCLUSIONS: Our study indicates a stimulus-response effect according to the type and number of DHRCs. This indicates potential for risk-stratification within HR PCa patients that could be applied in clinical decision making to increase or reduce treatment intensity.

Cancer-specific Mortality After Cryoablation vs Heat-based Thermal Ablation in T1a Renal Cell Carcinoma.

PURPOSE: Guidelines suggest less favorable cancer control outcomes for local tumor destruction in T1a renal cell carcinoma patients with tumor size 3.1-4 cm. We compared cancer-specific mortality between cryoablation vs heat-based thermal ablation in patients with tumor size 3.1-4 cm, as well as in patients with tumor size ≤3 cm. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2018), we identified patients with clinical T1a stage renal cell carcinoma treated with cryoablation or heat-based thermal ablation. After up to 2:1 ratio propensity score matching between patients treated with cryoablation vs heat-based thermal ablation, we addressed cancer-specific mortality relying on competing risks regression models, adjusted for other-cause mortality and other covariates (age, tumor size, tumor grade, and histological subtype). RESULTS: Of 1,468 assessable patients with tumor size 3.1-4 cm, 1,080 vs 388 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 757 cryoablations vs 388 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was associated with higher cancer-specific mortality (HR:2.02, P < .001), relative to cryoablation. Of 4,468 assessable patients with tumor size ≤3 cm, 3,354 vs 1,114 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 2,217 cryoablations vs 1,114 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was not associated with higher cancer-specific mortality (HR:1.13, P = .5) relative to cryoablation. CONCLUSIONS: Our findings corroborated that in cT1a patients with tumor size 3.1-4 cm, cancer-specific mortality is twofold higher after heat-based thermal ablation vs cryoablation. Conversely, in patients with tumor size ≤3 cm either ablation technique is equally valid. These findings should be considered at clinical decision making and informed consent.

Outcome of patients with epithelialized cavity formation after excessive vesicourethral anastomotic leak post radical prostatectomy.

PURPOSE: Excessive vesicourethral anastomotic leak (EVAL) is a rare but severe complication after radical prostatectomy (RP). Epithelialized vesicourethral cavity formation (EVCF) usually develops during prolonged catheterization. To our knowledge, there is no description of postoperative outcomes, complications, or functional assessment of these patients who received conservative therapy after EVAL. METHODS: We identified 70 patients (0.56%) with radiographic evidence of EVCF out of 12,434 patients who received RP in 2016-2020 at our tertiary care center. Postoperative radiographic cystograms (CG) were retrospectively re-examined by two urologists individually. We assessed urinary continence (UC), the need for intervention due to anastomotic stricture formation, urinary tract infection (UTI), and symphysitis during the first year of follow-up post-RP. RESULTS: The median age was 66 years [interquartile range (IQR) 61-70 years], the median body mass index was 27.8 kg/m2 (IQR 25.5-30.3 kg/m2), and the median prostate specific antigen before RP was 7.1 ng/ml (IQR 4.7-11.8 ng/ml). The median catheter insertion time was 44.5 days (IQR 35.2-54 days). One-year continence follow-up was available for 27 patients (38.6%), of which 22 (81.5%) reported the use of ≤ one pad, two patients reported the use of two (7.4%) pads/24 h, and three (11.1%) patients reported use > two pads/24 h. Overall, four (5.7%) patients needed surgical reintervention for anastomotic stricture, eight (11.5%) patients presented with symphysitis, and 55 (77.1%) presented with UTI. CONCLUSION: UC in 81.5% 1-year post-RP suggests that conservative treatment in EVAL is a treatment option with an acceptable outcome on UC and should be considered before reintervention for anastomotic insufficiency.

Rates of metastatic prostate cancer in newly diagnosed patients: Numbers needed to image according to risk level.

BACKGROUND: The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown. METHODS: Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed. RESULTS: Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1a-c ), 8920 (4.9%) harbored M1a-c stage: 50 (0.07%), 45 (0.1%), 161 (0.5%), 1290 (5.1%), and 7374 (22.0%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk. These resulted in NNI of 1347, 602, 174, 20, and 5, respectively. CONCLUSIONS: Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients.

BACKGROUND: The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP. RESULTS: Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001). CONCLUSIONS: In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG.

Grade and stage misclassification in intermediate unfavorable-risk prostate cancer radiotherapy candidates.

BACKGROUND: We tested for upgrading (Gleason grade group [GGG] ≥ 4) and/or upstaging to non-organ-confined stage ([NOC] ≥ pT3/pN1) in intermediate unfavorable-risk (IU) prostate cancer (PCa) patients treated with radical prostatectomy, since both change the considerations for dose and/or type of radiotherapy (RT) and duration of androgen deprivation therapy (ADT). METHODS: We relied on Surveillance, Epidemiology, and End Results (2010-2015). Proportions of (a) upgrading, (b) upstaging, or (c) upgrading and/or upstaging were tabulated and tested in multivariable logistic regression models. RESULTS: We identified 7269 IU PCa patients. Upgrading was recorded in 479 (6.6%) and upstaging in 2398 (33.0%), for a total of 2616 (36.0%) upgraded and/or upstaged patients, who no longer fulfilled the IU grade and stage definition. Prostate-specific antigen, clinical stage, biopsy GGG, and percentage of positive cores, neither individually nor in multivariable logistic regression models, discriminated between upgraded and/or upstaged patients versus others. CONCLUSIONS: IU PCa patients showed very high (36%) upgrading and/or upstaging proportion. Interestingly, the overwhelming majority of those were upstaged to NOC. Conversely, very few were upgraded to GGG ≥ 4. In consequence, more than one-third of IU PCa patients treated with RT may be exposed to suboptimal dose and/or type of RT and to insufficient duration of ADT, since their true grade and stage corresponded to high-risk PCa definition, instead of IU PCa. Data about magnetic resonance imaging were not available but may potentially help with better stage discrimination.

Contemporary seminal vesicle invasion rates in NCCN high-risk prostate cancer patients.

BACKGROUND: Contemporary seminal vesicle invasion (SVI) rates in National Cancer Comprehensive Network (NCCN) high-risk prostate cancer (PCa) patients are not well known but essential for treatment planning. We examined SVI rates according to individual patient characteristics for purpose of treatment planning. MATERIALS AND METHODS: Within Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), 4975 NCCN high-risk patients were identified. In the development cohort (SEER geographic region of residence: South, North-East, Mid-West, n = 2456), we fitted a multivariable logistic regression model predicting SVI. Its accuracy, calibration, and decision curve analyses (DCAs) were then tested versus previous models within the external validation cohort (SEER geographic region of residence: West, n = 2519). RESULTS: Out of 4975 patients, 28% had SVI. SVI rate ranged from 8% to 89% according to clinical T stage, prostate-specific antigen (PSA), biopsy Gleason Grade Group and percentage of positive biopsy cores. In the development cohort, these variables were independent predictors of SVI. In the external validation cohort, the current model achieved 77.6% accuracy vs 73.7% for Memorial Sloan Kettering Cancer Centre (MSKCC) vs 68.6% for Gallina et al. Calibration was better than for the two alternatives: departures from ideal predictions were 6.0% for the current model vs 9.8% for MSKCC vs 38.5% for Gallina et al. In DCAs, the current model outperformed both alternatives. Finally, different nomogram cutoffs allowed to discriminate between low versus high SVI risk patients. CONCLUSIONS: More than a quarter of NCCN high-risk PCa patients harbored SVI. Since SVI positivity rate varies from 8% to 89%, the currently developed model offers a valuable approach to distinguish between low and high SVI risk patients.

Contemporary vs historical survival rates in metastatic clear cell renal carcinoma according to race/ethnicity.

PURPOSE: Systemic therapies (ST) improved contemporary survival rates, relative to historical in clear cell metastatic renal carcinoma (ccmRCC) patients. The magnitude of this improvement is unknown according to race/ethnicity. METHODS: Within the SEER registry (2000-2017), ccmRCC patients were stratified according to race/ethnicity (Caucasian, Hispanic, African American, Asian) and historical (2000-2009) vs contemporary (2010-2017) years of diagnosis. Competing risks regression (CRR) with adjustment for other-cause mortality and Poisson smoothed cumulative incidence plots addressed cancer-specific mortality (CSM). RESULTS: Of 10,141 mRCC patients, 4316 (43%) vs 5825 (57%) were diagnosed in historical vs contemporary era. Of 4316 historical patients, 3203 (74%) vs 593 (14%) vs 293 (7%) vs 227 (5%) were Caucasian, Hispanic, African American and Asian. Of 5825 contemporary patients, 4124 (71%) vs 977 (17%) vs 362 (6%) vs 362 (6%) were Caucasian, Hispanic, African American and Asian. Between 2000 and 2017, ST rates ranged from 12 to 57% in Caucasians, 2 to 57% in Hispanics, 33 to 50% in African Americans, 17 to 70% in Asians and universally increased toward a plateau in 2010. In Caucasians, CSM decreased from 80 to 74% vs 79 to 74% in Hispanics vs 79 to 77% in African Americans, but not in Asians (67-73%). Nonetheless, these rates translated into independent predictor status of contemporary years of diagnosis in all race/ethnicity groups: CSM hazard ratios of 0.75, 0.75, 0.73 and 0.80 in, respectively, Caucasian, Hispanic, African American and Asian. CONCLUSIONS: In all race/ethnicity groups, contemporary ST rates increased and improved CSM rates have also been recorded.

Outcomes of robotic-assisted versus open radical cystectomy in a large-scale, contemporary cohort of bladder cancer patients.

BACKGROUND AND OBJECTIVES: To test for differences in perioperative outcomes and total hospital costs (THC) in nonmetastatic bladder cancer patients undergoing open (ORC) versus robotic-assisted radical cystectomy (RARC). METHODS: We relied on the National Inpatient Sample database (2016-2019). Statistics consisted of trend analyses, multivariable logistic, Poisson, and linear regression models. RESULTS: Of 5280 patients, 1876 (36%) versus 3200 (60%) underwent RARC versus ORC. RARC increased from 32% to 41% (estimated annual percentage change [EAPC]: + 8.6%; p = 0.02). Rates of transfusion (8% vs. 16%), intraoperative (2% vs. 3%), wound (6% vs. 10%), and pulmonary (6% vs. 10%) complications were lower in RARC patients (all p < 0.05). Moreover, median length of stay (LOS) was shorter in RARC (6 vs. 7days; p < 0.001). Conversely, median THC (31,486 vs. 27,162$; p < 0.001) were higher in RARC. Multivariable logistic regression-derived odds ratios addressing transfusion (0.49), intraoperative (0.53), wound (0.68), and pulmonary (0.71) complications favored RARC (all p < 0.01). In multivariable Poisson and linear regression models, RARC was associated with shorter LOS (Rate ratio:0.86; p < 0.001), yet higher THC (Coef.:5,859$; p < 0.001). RARC in-hospital mortality was lower (1% vs. 2%; p = 0.04). CONCLUSIONS: RARC complications, LOS, and mortality appear more favorable than ORC, but result in higher THC. The favorable RARC profile contributes to its increasing popularity throughout the United States.

Robot-assisted reconstructive surgery of the distal ureter: single institution experience in 16 patients.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Open reconstructive surgery of the lower ureteric segment in adults often requires large incisions, as the basic prerequisite for such complex procedures is wide exposure. Published experience on minimally invasive techniques in this challenging surgical field, e.g. conventional laparoscopy or robot-assisted laparoscopy, still remains limited. We report our experience from one of the largest single institution series on robot-assisted reconstructive surgery of the distal ureter in adults, with a special focus on technical aspects of the different surgical procedures. OBJECTIVE: To describe the feasibility of and operative techniques used during different daVinci® robot-assisted laparoscopic reconstructive procedures of the distal ureter, and to report the short-term outcome of such procedures. PATIENTS AND METHODS: Between June 2009 and October 2011, 16 patients underwent robot-assisted operations of the distal ureter because of various underlying pathological conditions. We present a description of each procedure, the incidence of perioperative complications and the results of follow-up examination. The data were collected retrospectively using the patients' records and questionnaires sent to the patients and the referring urologists. The follow-up examinations were done at the discretion of the referring urologists. RESULTS: The surgical indications and operative techniques were as follows: seven distal ureteric resections [DUR] with psoas hitch procedures (+/- Boari flap; four), extravesical reimplantation (two) or end-to-end anastomosis (one) because of benign distal ureteric stricture; four DUR with psoas hitch procedure (+/- Boari flap) and pelvic lymphadenectomy for urothelial carcinoma of the ureter; one DUR with psoas hitch procedure and Boari flap because of unexpected locally recurrent prostate cancer; one extravesical reimplantation because of vesico-ureteric reflux; one bilateral intravesical reimplantation of ectopic ureters (as part of a radical prostatectomy); one resection of a non-functioning upper kidney pole with associated megaureter and ureterocele and intravesical reimplantation of lower pole ureter; one resection of pelvic endometriosis and ureterolysis with omental wrap. The median operative duration (including docking/undocking of the robot) was 260 min. There were no intraoperative complications but there was one conversion to open surgery. Complications according to the Clavien-Dindo classification occurred in 12 patients (75%) ≤ 90 days of surgery: 10 (62%) minor (grade I-II) and two (12%) major complications (grades IIIb and IVa, respectively). The median hospital stay after surgery was 7.5 days. At a median follow-up of 10.2 months, 15 patients (94%) remained without signs of urinary tract obstruction and 13 (81%) were asymptomatic. CONCLUSIONS: Robot-assisted reconstructive surgery of the distal ureter is feasible and can be used without compromising the generally accepted principles of open surgical procedures. The functional outcome was good in short-term follow-up and severe postoperative complications were rare.

The effect of chemotherapy in sarcomatoid bladder cancer patients treated with radical cystectomy.

INTRODUCTION: Data about the role of chemotherapy in sarcomatoid bladder cancer (SBC) are limited. We addressed the effect of chemotherapy in non-metastatic SBC patients treated with radical cystectomy (RC). METHODS: Using the Surveillance, Epidemiology, and End Results database (2001-2018), we identified 331 patients with non-metastatic muscle-invasive or higher SBC (T2-4N0-3M0). Kaplan-Meier plots and Cox regression models tested cancer-specific mortality (CSM ). Sample size and power analyses tested for power limitations. RESULTS: Of 331 SBC patients, 129 (38.9%) were exposed to chemotherapy. The rate of organ-confined stage (T2N0M0) was 33% in both chemotherapy-exposed and chemotherapy-naive patients. In the overall cohort, median CSM-free survival was 84 months (interquartile range [IQR] 21-NA) vs. 26 months (IQR 17-84) in chemotherapy exposed vs. chemotherapy-naive patients, respectively. In multivariable Cox regression models, chemotherapy was associated with lower CSM, without reaching statistical significance (hazard ratio [HR ] 0.72, confidence interval [CI] 0.51-1.01, p=0.054). In subgroup analyses, chemotherapy exposure in organ-confined (n=110) vs. non-organ-confined (n=221) patients resulted in a HR of 0.51 (p=0.12) vs. 0.77 (p=0.17), respectively. Power analyses, based on two-sided α=0.05, revealed values of 52%, 14%, and 43% in the entire population, organ-confined, and nonorgan-confined subgroups, respectively. CONCLUSIONS: In non-metastatic SBC treated with RC, the association between chemotherapy and lower CSM is particularly strong in organ-confined stage. A substantially larger cohort would be required to confirm the statistical significance of the recorded protective effect of chemotherapy.

The association of the type and number of D'Amico high-risk criteria with rates of pathologically non-organ-confined prostate cancer.

Introduction: The aim of this study was to assess the association between the type and number of D'Amico high-risk criteria (DHRCs) with rates of pathologically non-organ-confined (NOC) prostate cancer in patients treated with radical prostatectomy (RP) and pelvic lymphadenectomy (PLND). Material and methods: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 12961 RP and PLDN patients with at least one DHRC. We relied on descriptive statistics and multivariable logistic regression models. Results: Of 12 961 patients, 6135 (47%) exclusively harboured biopsy Gleason score (GS) 8-10, 3526 (27%) had clinical stage ≥T2c, and 1234 (9.5%) had prostate-specific antigen (PSA) >20 ng/mL. Only 1886 (15%) harboured any combination of 2 DHRCs. Finally, all 3 DHRCs were present in 180 (1.4%) patients. NOC rates increased from 32% for clinical T stage ≥T2c to 49% for either GS 8-10 only or PSA >20 ng/mL only and to 66-68% for any combination of 2 DHRCs, and to 84% for respectively all 3 DHRCs, which resulted in a multivariable logistic regression OR of 1.00, 2.01 (95% CI 1.85-2.19; p <0.001), 4.16 (95% CI 3.69-4.68; p <0.001), and 10.83 (95% CI 7.35-16.52; p <0.001), respectively. Conclusions: Our study indicates a stimulus-response effect according to the type and number of DHRCs. Hence, a formal risk-stratification within high-risk prostate cancer patients should be considered in clinical decision-making.

Collecting duct carcinoma: Epidemiology, clinical characteristics and survival.

INTRODUCTION: Collecting duct carcinoma (CDC) is a rare renal malignancy. We relied on a large population-based cohort to address epidemiology, clinical characteristics, and treatment of CDC patients. We also tested survival in the overall cohort, as well as in stage-specific fashion. MATERIALS AND METHODS: Within Surveillance, Epidemiology, and End Results (2004-2018) database, we identified 399 CDC patients. Based on Kaplan-Meier plots survival estimates, conditional survival rates were derived according to disease stage. Cox regression models tested for predictors of cancer specific mortality (CSM). RESULTS: Overall, 273 (68.4%) patients were male, 236 (59.2%) had T3-4 stages, 148 (37.1%) had lymph node invasion, and 156 (39.1%) had distant metastases at initial diagnosis. Nephrectomy alone was commonest in stage I-II (n = 91/99, 92%) and III (n = 94/116, 81%). Combination of both nephrectomy and systemic therapy was commonest in stage IV (n = 62/172, 36%). In the overall cohort, median cancer specific survival was 18 months. Provided a disease-free interval of 24 months, five-year Kaplan-Meier estimated survival at diagnosis increased from 74.2 to 91.0% in stage I-II, from 31.1 to 65.3% in stage III, and from 6.3 to 34.1% in stage IV. In multivariable Cox regression models addressing CSM, systemic therapy (Hazard Ratio [HR]: 0.47, P = 0.020), nephrectomy (HR: 0.37, P < 0.001) and combination of both (HR: 0.28, P < 0.001) exhibited a strong protective effect. CONCLUSION: Despite its highly aggressive phenotype and dismal survival, CDC is sensitive to nephrectomy and/or systemic therapy. Moreover, even for advanced stage, a more favorable prognosis can be achieved in patients, who benefit of disease-free interval after diagnosis and initial treatment.

Cancer specific mortality in patients with collecting duct vs. clear cell renal carcinoma.

BACKGROUND: Collecting duct carcinoma (CDC) is biologically more aggressive than clear cell renal cell carcinoma (ccRCC). We tested for differences in cancer specific mortality (CSM) rates according to CDC vs. ISUP (International Society of Urological Pathology) 4 ccRCC histological subtype. We hypothesized that the survival disadvantage still applies, even after most detailed adjustments. METHODS: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 380 CDC vs. 6273 ISUP 4 ccRCC patients of all stages. Propensity score matching (age, sex, race/ethnicity, T, N, and M stages, nephrectomy, and systemic therapy status), Kaplan-Meier plots and multivariable Cox regression models were used. RESULTS: All 380 CDC were matched (1:2) with 760 ISUP4 ccRCC patients. Prior to matching CDC patients exhibited higher rates of lymph node invasion (37.6 % vs. 14.7 %, p < 0.001), and of distant metastases (40.8 % vs. 30.4 %, p < 0.001). Systemic therapy rates were higher in CDC (29.5 % vs. 20.5 %, p < 0.001). However, nephrectomy rates were higher in ISUP4 ccRCC patients (97.5 % vs. 84.7 %, p < 0.001). After matching, in multivariable Cox regression models addressing CSM, CDC was associated with a HR of 1.5 (p < 0.001) in the overall population vs. 1.9 (p = 0.014) in stage I-II vs. 1.4 (p = 0.022) in stage III vs. 1.6 in stage IV (p < 0.001), relative to ISUP4 ccRCC. CONCLUSION: CDC patients exhibited 40-90 % higher CSM than their ISUP4 ccRCC counterparts in the overall analysis, as well as in stage specific analyses. The CSM disadvantage applies despite higher rates of systemic therapy in CDC patients.

Radical cystectomy in non-metastatic sarcomatoid bladder cancer: A direct comparison vs urothelial bladder cancer.

INTRODUCTION: The effect of radical cystectomy (RC) on cancer-specific mortality (CSM) is unclear in non-metastatic sarcomatoid bladder cancer (SBC) patients. We aimed to test the benefit of RC in SBC, and to perform a direct comparison vs urothelial bladder cancer (UCB). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (SEER 2001-2018) all non-metastatic SBC and UBC patients were identified. Endpoint of interest was CSM. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, three-months landmark analyses, and sensitivity analyses were performed. All results were stratified according to organ-confined (OC: T2N0M0) vs non-organ-confined (NOC: T3-4N0M0 or TanyN1-3M0) stages. RESULTS: Of 554 SBC patients, 49 vs 51% harbored OC vs NOC stages. Of 47,741 UBC patients, 62 vs 38% harbored OC vs NOC stages. RC rates were 33 vs 67% in OC vs NOC-SBC patients, and 40 vs 60% in OC vs NOC-UBC patients. After 1:1 PSM, comparison between RC vs no-RC was performed in OC-SBC (67 patients per group), OC-UBC (7611 patients per group), NOC-SBC (63 patients per group), and NOC-UBC patients (4644 patients per group). CRR hazard ratios associated with RC vs no-RC were 0.37 (p < 0.001) in OC-SBC vs 0.45 (p < 0.001) in OC-UBC, and 0.56 (p = 0.01) in NOC-SBC vs 0.68 (p < 0.001) in NOC-UBC. These results were replicated in sensitivity and landmark analyses. CONCLUSIONS: The protective effect of RC vs no-RC is stronger in SBC than UBC patients, regardless of OC vs NOC stages.

Mortality According to Treatment in Metastatic Collecting Duct Renal Cell Carcinoma.

INTRODUCTION: Controlled contemporary analyses of mortality in metastatic collecting duct renal cell carcinoma (mcdRCC) are unavailable. We addressed this knowledge gap and tested rates of treatment and associated mortality in patients with mcdRCC. PATIENTS AND METHODS: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 155 mcdRCC patients. Kaplan-Meier plots and Cox proportional hazards regression models tested the effect of treatment (cytoreductive nephrectomy [CN] alone vs. systemic therapy [ST] alone vs. combination of both CN + ST) on overall mortality (OM). RESULTS: In the overall cohort (n = 155), 57 patients (37%) were treated with combination of both CN + ST, 46 (30%) underwent CN alone, 28 (18%) received ST alone, and 24 (15%) had none/unknown treatment. According to age categories (≤ 59 vs. 60-69 vs. ≥ 70 years), rates of combination of both CN + ST were 45% vs. 45% vs. 14%, respectively. CN alone was the most frequent type of treatment in patients aged ≥ 70 (50%). Median overall survival was 4.0 months for CN alone vs. 5.5 months for ST alone vs. 9.0 months for combination of both CN+ST. In multivariable Cox regression models, where CN alone was the referent, the use of ST alone and combination of both CN + ST were respectively associated with a HR of 0.74 (P = .3) and 0.43 (P < .001), after adjustment for all covariates. CONCLUSIONS: In mcdRCC patients, concomitant use of CN and ST results in lowest mortality, followed by ST alone, and CN alone. In consequence combination of both CN + ST should be recommended whenever applicable.

Cancer-specific Mortality in T1a Renal Cell Carcinoma Treated with Local Tumor Destruction Versus Partial Nephrectomy.

BACKGROUND: Large-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce. OBJECTIVE: To compare CSM after LTD versus PN. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), we identified patients with clinical T1a stage RCC treated with LTD or PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: After 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype). RESULTS AND LIMITATIONS: Relative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1-4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations. CONCLUSIONS: In T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1-4 cm than in those with tumor size ≤3 cm. PATIENT SUMMARY: In patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1-4 cm, but was also present in those with tumor size ≤3 cm.

Regional differences in total hospital costs for radical cystectomy in the United States.

OBJECTIVES: To test for regional differences in total hospital costs (THC) across the United States in bladder cancer patients treated with open radical cystectomy (ORC) or robotic-assisted radical cystectomy (RARC). MATERIALS: We relied on the National Inpatient Sample (NIS) database (2016-2019) and stratified RC patients according to census region (Midwest, Northeast, South, West). Primary statistical analyses consisted of THC-trend analyses and multivariable log-link linear regression models, after adjustment for hospital clustering (Generalized Estimating Equation function) and discharge disposition weighting. Finally, sensitivity analysis, relying on most favorable patient cohort, was performed. RESULTS: Of 5280 eligible patients, 1441 (27%), 1031 (20%), 1854 (35%) and 954 (18%) underwent RC in the Midwest, Northeast, South and West, respectively. Median THC was 28,915$ and differed significantly between regions (Midwest: 28,105$; Northeast: 28,886$; South: 26,096$; West: 38,809$; p < 0.001). After stratification between ORC and RARC, highest THC was invariably recorded in the West: ORC 36,137$ vs 23,941-28,850$ and RARC 43,119$ vs 28,425-29,952$ (both p < 0.05). In multivariable log-link linear regression models, surgery in the West was independently associated with higher THC: ORC (Exponent beta [Exp[ß]]: 1.39; 95%-CI: 1.32-1.47; p < 0.001) and RARC (Exp[ß]: 1.46; 95%-CI: 1.38-1.55; p < 0.001). Results remained unchanged when analyses were refitted in most favorable patient subgroup. CONCLUSIONS: Important regional differences in ORC and RARC THC distinguish the West from other United States regions. The THC discrepancy clearly requires closer examination to identify underlying processes that contribute to inflated costs in the West.

African American vs Caucasian race/ethnicity in adrenocortical carcinoma patients.

In some primaries, African American race/ethnicity predisposes to higher stage and worse survival. We tested for differences in cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with adrenocortical carcinoma (ACC) according to African American vs Caucasian race/ethnicity. We hypothesized that African Americans present with higher tumor stage and grade, do not receive the same treatment, and experience worse oncological outcomes than Caucasians. Within Surveillance, Epidemiology, and End Results database, we identified 1016 ACC patients: 123 (12.1%) African Americans vs 893 (87.9%) Caucasians. Propensity score matching (PSM) (age, sex, marital status, grade, T, N, and M stages, and treatment type), Poisson-smoothed cumulative incidence plots, and competing risk regression (CRR) were used. Compared to Caucasians, African Americans were more frequently unmarried (56.9% vs 35.5%, P < 0.001). No clinically meaningful or statistically significant differences were observed for age, grade, T, N, and M stages, as well as treatment type (all P > 0.05). After PSM (1:4), 123 African Americans and 492 Caucasians remained and were included in CRR analysis. In multivariable CRR models, CSM and OCM rates were not different between the two race/ethnicities (hazard ratio: 0.84, P = 0.3). In African Americans, 5-year CSM rates were 31.2% and 75.3% in European Network for the Study of Adrenal Tumors (ENSAT) stages I-II and III-IV, respectively vs 32.9% and 75.4% in Caucasians. Overall 5-year OCM rates were 11.0% vs 10.1% in respectively African Americans and Caucasians. Unlike other primaries, in ACC, African American race/ethnicity is not associated with higher disease stage at initial diagnosis or worse survival.