Assessing the Impact of Percutaneous Nephrostomy Presence on Neoadjuvant Treatment Quality in Patients With Muscle Invasive Bladder Cancer.

INTRODUCTION: Symptomatic hydronephrosis associated with muscle invasive bladder cancer (MIBC) necessitates percutaneous nephrostomy (PCN) insertion before neoadjuvant chemotherapy (NAC). This study assesses the impact of PCN presence on standard intended NAC quality, its related complications and outcome after radical cystectomy (RC). MATERIALS AND METHODS: The study comprises a retrospective, multicenter cohort of 193 consecutive RCs performed between 2016 and 2019. Eighty (42%) of these patients received NAC and were divided in 2 comparison groups by presence (n = 26; 33%) or absence (n = 54; 67%) of PCN. Endpoints included completion of adequate NAC treatment (cisplatin-based chemotherapy for at least 4 courses), complications during NAC, post-RC complications and hospital stay. RESULTS: Overall, patients with PCN (45/193; 23%) featured a higher referral rate to NAC (58% vs. 36%, P = .01), worse glomerular filtration rates (P < .001) and more adverse events (P = .04), in comparison to non-PCN patients. In the NAC cohort, PCN patients had less adequate treatment rates (54% vs. 85%, P = .005), and more infections (35% vs, 7%; P = .008) and hospitalizations (58% vs. 13%; P < .001) during chemotherapy. Post-RC outcome was similar for both comparison groups. PCN was an independent risk factor for inadequate NAC (OR = 3.9, P = .04), and infections (OR = 11.3, P = .01) and hospitalizations (OR = 7.5, P = .004) during NAC. CONCLUSIONS: PCN in MIBC patients is a significant risk factor for inadequate NAC and adverse events during treatment. This finding may quire the rationale of NAC, potentially leading to consideration of NAC avoidance and upfront RC in PCN patients. Further survival studies with long follow-up are needed for elucidating this issue.

The role of malnutrition universal screening tool in predicting outcomes after radical cystectomy.

PURPOSE: The Malnutrition Universal Screening Tool integrates body mass index, unintentional weight loss and present illness to assess risk for malnutrition. The predictive role of 'MUST' among patients undergoing radical cystectomy is unknown. We investigated the role of 'MUST' in predicting postoperative outcomes and prognosis among patients after RC. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis of 291 patients who underwent radical cystectomy in 6 medical centers between 2015 and 2019. Patients were stratified to risk groups according to the 'MUST' score [low risk (n = 242) vs. medium-to-high risk (n = 49)]. Baseline characteristics were compared between groups. Endpoints were 30-day postoperative complications rate, cancer-specific-survival and overall survival. Kaplan-Meier curves and Cox-regression analyses were used to evaluate survival and identify predictors of outcomes. RESULTS: Median age of the study cohort was 69 years (IQR 63-74). Median duration of follow up for survivors was 33 months (IQR 20-43). Thirty-day major postoperative complications rate was 17%. Baseline characteristics were not different between the 'MUST' groups, and there was no difference in early post-operative complication rates. CSS and OS were significantly lower (p ≤ 0.02) in the medium-to-high-risk group ('MUST' score≥1) with estimated 3-year CSS and OS rates of 60% and 50% compared to 76% and 71% in the low-risk group, respectively. On multivariable analysis, 'MUST'≥1 was an independent predictor of overall- (HR = 1.95, p = 0.006) and cancer-specific-mortality (HR = 1.74, p = 0.05). CONCLUSIONS: High 'MUST' scores are associated with decreased survival in patients after radical cystectomy. Thus, the 'MUST' score may serve as a preoperative tool for patient selection and nutritional intervention.

Reply to Veerman et al. Comment on "Rosenzweig et al. Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates. J. Pers. Med. 2022, 12, 410".

We thank the commenters for their important insights [...].

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates.

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with "negative" prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with "negative" pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an "intense" prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a "negative" uptake (in the study group), and 45 (46%) had a "positive" uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates.

Stereotactic ablative radiation therapy for renal cell carcinoma with inferior vena cava tumor thrombus.

BACKGROUND: Inferior vena cava tumor thrombus (IVC-TT) is a rare yet deadly sequel of renal cell carcinoma (RCC) with limited treatment options. The standard treatment is extirpative surgery, which has high rates of morbidity and mortality. As a result, many patients are unfit or unwilling to undergo surgery and face poor prognosis. This stresses the need for alternative options for local disease control. Our study aims to assess the feasibility and oncological outcomes of stereotactic ablative radiation (SAbR) for IVC-TT. METHODS: A retrospective study reviewing six leading international institutions' experience in treating RCC with IVC-TT with SAbR. Primary end point was overall survival using Kaplan-Meier. RESULTS: Fifteen patients were included in the cohort. Over 50% of patients had high level IVC-TT (level III or IV), 66.7% had metastatic disease. Most eschewed surgery due to high surgical risk (7/15) or recurrent thrombus (3/15). All patients received SAbR to the IVC-TT with a median biologically equivalent dose (BED10) of 72 Gy (range: 37.5-100.8) delivered in a median of 5 fractions (range 1-5). Median overall survival was 34 months. Radiographic response was observed in 58% of patients. Symptom palliation was recorded in all patients receiving SAbR for this indication. Only grade 1 to 2 adverse events were noted. CONCLUSIONS: SAbR for IVC-TT appears feasible and safe. In patients who are not candidates for surgery, SAbR may palliate symptoms and improve outcomes. SAbR may be considered as part of a multimodal treatment approach for patients with RCC IVC-TT.

Nutritional Status Impairment Due to Neoadjuvant Chemotherapy Predicts Post-Radical Cystectomy Complications.

BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer (MIBC). Neoadjuvant chemotherapy (NAC) is associated with improved patient survival. The impact of NAC on nutritional status is understudied, while the association between malnutrition and poor surgical outcomes is well known. This study aims to examine the association between NAC, nutritional status impairment, and post-operative morbidity. MATERIALS AND METHODS: We included MIBC patients who underwent RC and received NAC from multiple academic centers in Israel. Cross-sectional imaging was used to measure the psoas muscle area and normalized it by height (smooth muscle index, SMI). Pre- and post-NAC SMI difference was calculated (represents nutritional status change). The primary outcomes were post-RC ileus, infection, and a composite outcome of any complication. Logistic regression models were fit to identify independent predictors of the outcomes. RESULTS: Ninety-one patients were included in the study. The median SMI change was -0.71 (-1.58, -0.06) cm2/m2. SMI decline was significantly higher in patients with post-RC complications (-18 vs. -203, p < 0.001). SMI change was an independent predictor of all complications, ileus, infection, and other complications. The accuracy of SMI change for predicting all complications, ileus, infection, and other complications was 0.85, 0.87, 0.75, and 0.86, respectively. CONCLUSIONS: NAC-related nutritional deterioration is associated with increased risk of complications after RC. Our results hint towards the need for nutritional intervention during NAC prior to RC.

[DOES CHOOSING BETWEEN DUSTING OR FRAGMENTATION DURING LASER LITHOTRIPSY OF URINARY STONES CHANGE THE LONG TERM RESULTS?]

INTRODUCTION: Variations in laser pulse energy and it's frequency during lithotripsy, affect the rate and the method of stone breaking. The main modes of lithotripsy are dusting and fragmentation. AIMS: Comparison between long term results of dusting versus fragmentation, by defining the stone free rate (SFR) for each method and the time period until re-treatment need. METHODS: Clinical and radiological follow-up of 43 patients who underwent laser intervention using dusting or fragmentation. Both groups shared similar demographic features, stone sizes and locations. For each group, the percentage of patients without stones requiring intervention during the follow-up period of 36 months was defined as a success parameter. The incidence of emergency department (ED) admissions and auxiliary interventions were assessed. RESULTS: Thirty-eight patients were included in the study. No difference in the median period of time to clinically significant stone was seen (p=0.213). No difference was found in SFR between the dusting (83.3%) and the fragmentation (84.6%) groups respectively (p=1.000). No statistically significant difference was shown in ED admissions due to renal colic occurring in 31.6% and 10.5% within dusting and fragmentation groups respectively (p=0.116). CONCLUSIONS: No difference in time period until clinically significant stone appearance was seen. No significant difference in SFR was found between the groups at the long term follow-up. DISCUSSION: It seems that within the dusting group, the ED admission rate could be somewhat higher. However, this impression lacks statistical significance. A long term prospective study with a larger population is needed to confirm these results.

Predictive model for systemic recurrence following cisplatin-based neoadjuvant chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly used prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Systemic recurrence (SR) carries a dismal prognosis. We sought to determine risk factors associated with SR in this setting. METHODS: We evaluated a multi-center database of patients with UTUC who received cisplatin-based NAC before RNU. Final pathology at RNU was dichotomized into ypT<2 vs ypT≥2. Univariable and multivariable analyses were performed to identify risk factors associated with SR. Three groups were defined based on the number of significant risk factors (groups 1, 2, 3 for 0-1, 2, 3 risk factors, respectively) and evaluated for recurrence-free survival (RFS) using the Kaplan-Meier method. RESULTS: 106 patients were identified between 2004 and 2018. Median age was 67.0 years [IQR = 61-73.3]; 57 (54%) and 49 (46 %) patients received MVAC and GC, respectively. Final pathological stage was ypT<2 in 57 (54%); 23% (24/106) had SR. On univariable analysis, pathological variables on final specimen including ypT≥2, lymphovascular invasion (ypLVI), and nodal involvement were associated with SR. On multivariable analysis, ypLVI OR = 4.1 (95% CI 1.2-13.6; P = 0.024) and pathological nodal involvement OR = 4.5 (95% CI 1.3-15.7; P = 0.017) were predictive of recurrence. Stratifying by the number of risk factors, the 2-year RFS was 95%, 55%, and 18% for groups 1, 2, and 3 respectively (log-rank <0.001). CONCLUSION: This model evaluates the risk of SR following NAC and RNU to guide counseling and decision-making after surgery. Adverse pathological variable including ypLVI and nodal involvement, in combination with ypT-stage, are strongly associated with SR.

Neoadjuvant SABR for Renal Cell Carcinoma Inferior Vena Cava Tumor Thrombus-Safety Lead-in Results of a Phase 2 Trial.

PURPOSE: To evaluate the feasibility, safety, oncologic outcomes, and immune effect of neoadjuvant stereotactic radiation (Neo-SAbR) followed by radical nephrectomy and thrombectomy (RN-IVCT). METHODS AND MATERIALS: These are results from the safety lead-in portion of a single-arm phase 1 and 2 trial. Patients with kidney cancer (renal cell carcinoma [RCC]) and inferior vena cava (IVC) tumor thrombus (TT) underwent Neo-SAbR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. Absence of grade 4 to 5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathologic and immunologic alterations attributable to SAbR. RESULTS: Six patients were included in the final analysis. No grade 4 to 5 AEs were observed. A total of 81 AEs were reported within 90 days of surgery: 73% (59/81) were grade 1, 23% (19/81) were grade 2, and 4% (3/81) were grade 3. After a median follow-up of 24 months, all patients are alive. One patient developed de novo metastatic disease. Of 3 patients with metastasis at diagnosis, 1 had a complete and another had a partial abscopal response without the concurrent use of systemic therapy. Neo-SABR led to decreased Ki-67 and increased PD-L1 expression in the IVC-TT. Inflammatory cytokines and autoantibody titers reflecting better host immune status were observed in patients with nonprogressive disease. CONCLUSIONS: Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment correlated with abscopal response to SABR and RCC relapse-free survival, though direct causal relation to SABR has yet to be established.

Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.

Does grossly complete transurethral resection improve response to neoadjuvant chemotherapy?

INTRODUCTION: There is controversy regarding the benefit of a grossly complete transurethral resection of bladder tumor (TURBT) for muscle-invasive bladder cancer (MIBC) in patients prior to neoadjuvant chemotherapy (NAC). Advocates for this approach suggest a higher response rate to NAC, while others suggest this can increase the surgical risk for no clear benefit. METHODS: We retrospectively reviewed our institutional radical cystectomy (RC) database from 2011 to 2018 for patients who received an adequate course of cisplatin-based NAC for nonmetastatic MIBC. Univariable and multivariable logistic regression analyses were performed to identify factors associated with complete response [ypT0] or no residual muscle invasive bladder cancer [ypT < 2] following NAC based on clinicopathologic characteristics and grossly complete or incomplete TURBT. RESULTS: A total of 167 patients received NAC followed by RC for MIBC during the study period and 100 patients were included in the analysis due to known status of the completeness of TURBT-of these 49 patients underwent complete resection while 51 patients underwent incomplete resection prior to NAC. There were no significant differences in baseline clinicopathologic characteristics between patients who had complete vs. incomplete TURBT. At the time of RC, the overall ypT0 rate was 24% (n = 24), while the overall rate of ypT < 2 was 45%. On logistic regression, there was no association between completeness of TURBT and ypT0 or ypT < 2. Age, histology, and organ-confined disease were not significantly associated with response to NAC. Only smoking status (current or prior history) was negatively associated with ypT0 on univariable and multivariable analysis (odds ratio = 0.36, 95% confidence interval: [0.14-0.91], P = 0.031). CONCLUSION: We found no association between response to cisplatin-based NAC and completeness of TURBT in a cohort of MIBC patients. The study is limited by its retrospective nature and lack of ability to predict response to NAC based on TURBT tissue evaluation.

Intraoperative prophylactic intravesical chemotherapy to reduce bladder recurrence following radical nephroureterectomy.

PURPOSE: Single, postoperative instillation of prophylactic intravesical chemotherapy (pIVC) is effective in reducing bladder cancer recurrences following radical nephroureterectomy (RNU). Despite high level evidence, pIVC is underutilized. Intraoperative pIVC (I-pIVC) may be easier and safer to implement than postoperative pIVC (P-pIVC). We aimed to evaluate the efficacy of I-pIVC during RNU. MATERIALS AND METHODS: Retrospective analysis of patients undergoing RNU and I-pIVC or postoperative pIVC (P-pVC) with 20 to 40 mg mitomycin-C or 1 to 2 g gemcitabine. Recurrence rates were evaluated using the Kaplan-Meier curves and log rank test. Cox regression was used for univariable and multivariable analysis. RESULTS: One hundred and thirty-seven patients were included in the final analysis. 81% (111/137) had I-pIVC and 19% (26/137) had P-pIVC. In the I-pIVC group higher rates of HG, muscle invasive disease and gemcitabine use were observed. Overall, 74% (101/137) and 26% (36/137) had mitomycin-C and gemcitabine instillations, respectively. Within 12 months 14% (19/137) of the patients experienced bladder recurrence. Median time to bladder recurrence was 7 months (range 3-27). Twelve months bladder recurrence-free survival rates were 82% for the I-pIVC group, and 72% for the P-pIVC group ((log rank P = 0.365). CONCLUSIONS: I-pIVC during RNU may reduce bladder recurrence rates. Bladder recurrence rates are comparable to those reported using postoperative instillations. Intraoperative instillations may be easier to implement and may increase usage rates.

Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma.

OBJECTIVE: Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy. METHODS: We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression. RESULTS: 234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS). CONCLUSIONS: Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.

Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database.

OBJECTIVES: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC. METHODS: From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes. RESULTS: Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN. CONCLUSION: Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.

Nationwide Patterns of Care for Stage II Nonseminomatous Germ Cell Tumor of the Testicle.

BACKGROUND: Management strategies for advanced testicular cancer published from a few, high-volume clinical centers may not be generalizable. OBJECTIVE: To discern treatment patterns for stage II nonseminomatous germ cell tumor (NSGCT) in a nationwide cancer registry. DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Database was queried for patients with a stage II NSGCT from 2004 to 2014. Patients were stratified by clinical nodal status: cN1/stage IIA, cN2/stage IIB, and cN3/stage IIIC. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was performed to determine factors independently associated with primary retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and postchemotherapy RPLND (PC-RPLND). RESULTS AND LIMITATIONS: A total of 2203 patients (stages IIA, n=1060; IIB, n=869; and IIC, n=274) met the inclusion criteria. Overall, 83% of patients underwent primary chemotherapy, while 17% underwent primary RPLND. Stratified by stage, use of primary chemotherapy was 78%, 88%, and 86% for stages IIA, IIB, and IIC, respectively. Overall, 24% of patients underwent PC-RPLND. Factors independently associated with a lower likelihood of undergoing primary RPLND were a more recent diagnosis and a higher clinical nodal stage. Conversely, patients treated at high-volume facilities were more likely to receive primary RPLND. Factors associated with a higher likelihood of undergoing PC-RPLND included a higher clinical nodal stage, treatment at a high-volume center, and a greater distance of patient travel. Associations based on serum tumor markers could not be assessed. CONCLUSIONS: For clinical stage II NSGCT, nationwide utilization of primary chemotherapy is increasing compared with RPLND and is the preferred therapy for more advanced nodal disease. Primary RPLND may be underutilized in stage IIA disease. Utilization of PC-RPLND is driven by nodal stage as well as accessibility of a high-volume center. PATIENT SUMMARY: The use of primary retroperitoneal lymph node dissection (RPLND) in early nodal disease is declining, while upfront chemotherapy is increasingly utilized. Primary RPLND may identify patients who are actually pN0 and would not benefit from systemic chemotherapy. Primary RPLND and postchemotherapy RPLND are performed more frequently at centers of excellence.

Rational Approaches to Treatment Duration with Immunotherapy in Metastatic Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for metastatic renal cell carcinoma. The appropriate duration for ICI treatment is not clear, however. Analyses of landmark trials reveal that some patients exhibit sustained durable responses to ICIs even after treatment discontinuation, resulting in prolonged treatment-free intervals that can mitigate potential toxicities and the considerable financial burden associated with treatment. Adaptive approaches with PD1 monotherapy and combination immunotherapy tailored to tumor response are ongoing. More efforts will be needed to clarify the ideal ICI dosing regimen to maximize oncological benefit while minimizing treatment-related adverse effects and costs. PATIENT SUMMARY: We reviewed considerations surrounding treatment strategies when using immunotherapy to treat patients with kidney cancer. It is clear that some patients can experience prolonged cancer control when discontinuing immunotherapy. However, individualized approaches will be necessary to strike a balance between optimizing patient outcomes and reducing unnecessary side effects and cost.

Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma.

OBJECTIVE: To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). METHODS: Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. RESULTS: Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. CONCLUSION: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.

Preoperative predictive model and nomogram for disease recurrence following radical nephroureterectomy for high grade upper tract urothelial carcinoma.

PURPOSE: To identify preoperative risk factors for disease recurrence, following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), and to create a predictive nomogram. MATERIALS AND METHODS: Based on a multicenter database, we identified patients who underwent RNU due to high grade UTUC. Urothelial carcinoma of the bladder or contralateral UTUC was not considered as recurrence. Cox regression model was used to determine the effect of different preoperative variables as predictors of recurrence. RESULTS: Two hundred and forty-five patients were included in the analysis. The 2 and 5 years recurrence rates were 16.3% and 19.2%, respectively. Factors associated with recurrence on univariable analysis were sessile architecture hazard ratio (HR) 3.16 (95% CI, 1.38-7.26, P = 0.006), ≥cT3 disease HR 2.30 (95% CI, 1.12-4.72, P= 0.023), age >65 HR 2.02 (95% CI, 1.00-4.05, P= 0.048), Eastern Cooperative Group > 0 HR 1.98 (95% CI, 1.09-3.57, P= 0.023), hydronephrosis HR 1.93 (95% CI, 1.04-3.57, P= 0.035). Higher hemoglobin levels HR 0.81 (95% CI, 0.69-0.96, P= 0.013) and preoperative estimated glomerular filtration rate ≥ 50 HR 0.48 (95% CI, 0.25-0.92, P = 0.028) were associated with lower probability for recurrence. Multivariable analysis identified sessile architecture as the only independent predictor of recurrence HR 2.52 (95% CI, 1.09-5.86, P= 0.0308). C-index of 0.71 was calculated for a predictive model including all variables in the multivariable analysis, indicating good predictive accuracy. A nomogram predicting 2 and 5 year recurrence free probability was developed accordingly. CONCLUSIONS: Based on a multicenter database, we developed a nomogram with good predictive accuracy for recurrence following RNU. This may serve as an aid in decision-making regarding the use of neoadjuvant chemotherapy.

Impact of Hospital Case Volume on Outcomes Following Radical Nephrectomy and Inferior Vena Cava Thrombectomy.

BACKGROUND: Radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT) is a complicated procedure for which the impact of hospital case volume on overall survival (OS) is unknown. OBJECTIVE: To assess the degree to which renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) care is centralized and to evaluate the impact of hospital case volume on outcomes following RN-IVCT. DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Data Base was queried for patients with pT3b-c RCC treated with RN-IVCT. Hospitals were classified by case volume percentile as low (<75th percentile, <0.67 cases annually), intermediate (75th-95th percentile, 0.67-2.99 cases annually), or high (>95th percentile, >3 cases annually). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was OS. Secondary outcomes were short-term (30- and 90-d) mortality rates according to hospital case volume. Kaplan-Meier curves and Cox regression model were used to evaluate OS and the effect of covariables. RESULTS AND LIMITATIONS: There were 2664 cases of RN-IVCT for pT3b-c tumors reported by 573 institutions, of which 435, 108, and 30 were classified as low, intermediate, and high volume, accounting for 28.5%, 34.5%, and 37% of cases, respectively. Treatment at high-volume institutions was associated with better OS: the median OS was 42, 53, and 60 months for low, intermediate and high-volume centers, respectively (p=0.009). After multivariable adjustment, treatment at a high-volume institution was associated with a 24% relative risk reduction for all-cause mortality compared to treatment at a low-volume institution (hazard ratio 0.76, 95% confidence interval 0.65-0.89; p=0.001). There was no significant difference in short-term mortality following RN-IVCT when stratified by hospital case volume. CONCLUSIONS: Higher hospital case volume was associated with longer OS for patients undergoing RN-IVCT. These findings support efforts to centralize care for cases of advanced RCC. PATIENT SUMMARY: In this study we looked at the impact of hospital case volume on survival following surgery for renal cell carcinoma and inferior vena cava thrombectomy. Survival was significantly better in high-volume hospitals performing three or more procedures per year.