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.

[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.

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.

Site of extranodal metastasis impacts survival in patients with testicular germ cell tumors.

BACKGROUND: Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS: Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS: Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71. CONCLUSIONS: The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.

Effect of blue-light cystoscopy on contemporary performance of urine cytology.

OBJECTIVE: To evaluate the performance of urine cytology based on contemporary data, including the effect of enhanced cystoscopic techniques. MATERIALS AND METHODS: Individual patient data were obtained from three prospective studies: the Photocure (PC) B305 and the PC B308 studies, evaluating the use of blue-light cystoscopy with hexaminolevulinate (BLC-H), and the Cxbladder monitoring study, evaluating the Cxbladder monitor test for the detection of recurrent urothelial carcinoma. The specificity and sensitivity of cytology in each study and for the overall cohort were calculated. RESULTS: A total of 1 487 urine samples from 1 375 patients were included in the analysis; overall 615 tumours were detected correlating to 41% of the cytological specimens. The pooled sensitivity and specificity for cytology were 40.8% and 92.8%, respectively. The pooled sensitivity was 11.4% for low-grade/World Health Organization (WHO) grade 1 disease and 54.3% for high-grade/WHO grade 3 disease. There were no differences in cytology sensitivity based on the type of cystoscopy used, with sensitivity of 41.3% and 40.4% in white-light cystoscopy (WLC) and BLC-H, respectively. Subgroup analysis including carcinoma in situ ( CIS) showed a trend towards lower cytology sensitivity in BLC-H (54.5%) vs WLC (69.2%). CONCLUSIONS: Based on analysis of contemporary data, the sensitivity of cytology for detecting high-grade tumours and CIS remains low. On a per-patient analysis, cytology sensitivity was not affected by the use of advanced cystoscopic techniques except in patients with CIS. The use of cytology as the main adjunct to cystoscopy in patients at high risk can lead to missed opportunities for early detection of recurrence and for determining which patients are not responding to intravesical therapies such as bacille Calmette-Guérin.

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS: BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.

Diagnostic Performance of Prospectively Assigned Likert Scale Scores to Determine Extraprostatic Extension and Seminal Vesicle Invasion With Multiparametric MRI of the Prostate.

OBJECTIVE: The objective of this study was to determine the diagnostic performance of a prospectively assigned 5-point Likert scale for determination of extraprostatic extension (EPE) and seminal vesicle invasion (SVI). MATERIALS AND METHODS: This study was a single-center, retrospective analysis of prospectively collected data including all men with abnormal 3-T multiparametric MRI and subsequent radical prostatectomy between November 1, 2016, and September 30, 2017. Scores from a 5-point subjective Likert scale (1 = highly unlikely, 5 = highly likely) for the likelihood of EPE and SVI were prospectively assigned during clinical MRI interpretation. EPE and SVI status at whole-mount prostatectomy specimen served as the standard of reference. RESULTS: Among the 89 eligible men, whole-mount histopathology revealed organ-confined prostate cancer, EPE, and SVI in 49% (44/89), 46% (41/89), and 18% (16/89) of patients, respectively. Of the pathologically proven cases of EPE, 18% (2/11), 17% (4/24), 65% (17/26), 46% (6/13) and 80% (12/15) were assigned Likert scores of 1-5, respectively. Of the pathologically proven cases of SVI, 5% (3/58), 11% (2/18), 66% (2/3), 66% (2/3) and 100% (7/7) were assigned Likert scores of 1-5, respectively. The positive predictive values for scores of 4 or 5 were 64% for EPE and 90% for SVI. The negative predictive values for scores of 1 or 2 were 87% for EPE and 93% for SVI. Likert scores for EPE (odds ratio, 2.1; 95% CI, 1.3-3.4) and for SVI (odds ratio, 4.7; 95% CI, 2.3-9.6) were both associated with EPE and SVI on multivariate analysis. CONCLUSION: A 5-point Likert scale can effectively convey the degree of suspicion of EPE and SVI on multiparametric MRI of the prostate, facilitating informed decision-making.

Imaging for Screening and Surveillance of Patients with Hereditary Forms of Renal Cell Carcinoma.

PURPOSE OF REVIEW: To summarize the literature providing the basic genetic and clinical characteristics of renal cell carcinoma (RCC) familial syndromes, as well as to describe associated unique imaging characteristics and appropriate imaging protocols. RECENT FINDINGS: At least 5-8% of RCC cases are associated with hereditary syndromes. These patients are prone to developing multiple renal tumors or associated malignancies and require more intense diagnostic and follow-up imaging studies. New familial types of RCC are continuously discovered, vis-à-vis recent characterization of BAP1 associated RCC and MITF associated cancer syndrome. With increasing number of recognizable familial syndromes associated with RCC, physicians should be familiar with the different syndromes, the associated risks of malignancy and appropriate imaging protocols.

Retrospective Analysis of Laparoscopic Partial Nephrectomies Using the Zero Ischemia Technique.

PURPOSE: To report a series of 89 off-clamp laparoscopic partial nephrectomies (LPN) performed without using any additional "nephron sparing" manipulations. METHODS: Retrospective analysis of surgical characteristics, complications, postoperative results, and renal function changes. RESULTS: Between March 2008 and May 2014, 89 LPN using zero ischemia technique were performed. Most of the patients (61.8%) were male. The median age was 62 years (23-88). The mean BMI was 27.5 kg/m2 (20.8-54.2). The median tumor size was 3.0 cm (1.0-8.0). Tumor location was upper, middle, and lower part of the kidney in 33 (37.0%), 42 (47.2%), and 14 (15.7%) of patients, respectively. The median operative time was 154 min (58-289). The median hemoglobin change was -1.6 g/dL (0.5-5.5). The transfusion rate was 7.9%. The mean preoperative glomerular filtration rate was 96.6 mL/min (21.5-180.0) with a mean postoperative decline of 6.52 mL/min. The mean creatinine elevation after LPN was 0.09 mg/dL. The median hospital stay was 6 days (2-24). The intraoperative complications rate was 2.3%. Early postoperative complication rate was 33.7%. Late complications occurred in 6.7%. In 7 cases (7.9%), the surgical margins were microscopically involved by tumor cells. Conversion rate was 3.4%. CONCLUSION: Data obtained in the current series show that laparoscopic partial nephrectomy can be successfully performed without hilar clamping. Our results are comparable with contemporary data. Larger prospective studies would be helpful in assessing the evidence-based advantages of the "zero ischemia" technique.

Limited field noncontrast computerized tomography for followup of ureteral stones: initial results.

PURPOSE: Due to high specificity and sensitivity noncontrast computerized tomography is increasingly used to diagnose and follow patients with ureteral stones. We evaluated the feasibility of limited field noncontrast computerized tomography to follow patients with ureteral stones. MATERIALS AND METHODS: Included in the study were 71 patients who underwent diagnostic and followup noncontrast computerized tomography due to ureteral stones. According to stone position on the first diagnostic scan a limited field batch from the followup scan was formed and examined by an independent radiologist. Radiation doses and rates of potentially missed findings in the batch were compared to those of the full followup noncontrast scan. RESULTS: Average full followup noncontrast computerized tomography length was 46.5 cm and average batch length was 20.7 and 13.8 cm for proximal and distal stones, respectively. The average full followup noncontrast scan radiation dose was 12.2 mSv. Average batch doses were 6.1 and 4.1 mSv for proximal and distal stones, respectively (p = 0.002), resulting in a radiation exposure reduction of 48.8% for proximal stones and 66% for distal stones. In 3 cases additional clinical information (not including hydronephrosis) was missed when relying only on batch images. This additional information did not impact further urological treatment. CONCLUSIONS: Limited field noncontrast computerized tomography is a feasible option for following patients diagnosed with ureteral stones. It may lead to significantly lower radiation exposure.

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.

Adjuvant methods to improve results of local bladder irrigations by chemotherapy for NMIBC.

Non-muscle-invasive bladder cancer is characterized by frequent recurrences requiring repeated transurethral resections and carries a risk of progression to muscle-invasive disease. The routinely used, passive diffusion irrigation of the bladder with mitomycin C has achieved limited success in avoiding these events. We review two methods that may improve penetration of mitomycin C into the bladder wall, thus leading to better results in terms of recurrence rate and bladder preservation.

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 [...].

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.

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.