Multiplex imaging of localized prostate tumors reveals altered spatial organization of AR-positive cells in the microenvironment.

Mapping the spatial interactions of cancer, immune, and stromal cell states presents novel opportunities for patient stratification and for advancing immunotherapy. While single-cell studies revealed significant molecular heterogeneity in prostate cancer cells, the impact of spatial stromal cell heterogeneity remains poorly understood. Here, we used cyclic immunofluorescent imaging on whole-tissue sections to uncover novel spatial associations between cancer and stromal cells in low- and high-grade prostate tumors and tumor-adjacent normal tissues. Our results provide a spatial map of single cells and recurrent cellular neighborhoods in the prostate tumor microenvironment of treatment-naive patients. We report unique populations of mast cells that show distinct spatial associations with M2 macrophages and regulatory T cells. Our results show disease-specific neighborhoods that are primarily driven by androgen receptor-positive (AR+) stromal cells and identify inflammatory gene networks active in AR+ prostate stroma.

A Scaled Proteomic Discovery Study for Prostate Cancer Diagnostic Markers Using ProteographTM and Trapped Ion Mobility Mass Spectrometry.

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

SNPs at SMG7 Associated with Time from Biochemical Recurrence to Prostate Cancer Death.

BACKGROUND: A previous genome-wide association study identified several loci with genetic variants associated with prostate cancer survival time in two cohorts from Sweden. Whether these variants have an effect in other populations or if their effect is homogenous across the course of disease is unknown. METHODS: These variants were genotyped in a cohort of 1,298 patients. Samples were linked with age, PSA level, Gleason score, cancer stage at surgery, and times from surgery to biochemical recurrence to death from prostate cancer. SNPs rs2702185 and rs73055188 were tested for association with prostate cancer-specific survival time using a multivariate Cox proportional hazard model. SNP rs2702185 was further tested for association with time to biochemical recurrence and time from biochemical recurrence to death with a multi-state model. RESULTS: SNP rs2702185 at SMG7 was associated with prostate cancer-specific survival time, specifically the time from biochemical recurrence to prostate cancer death (HR, 2.5; 95% confidence interval, 1.4-4.5; P = 0.0014). Nine variants were in linkage disequilibrium (LD) with rs2702185; one, rs10737246, was found to be most likely to be functional based on LD patterns and overlap with open chromatin. Patterns of open chromatin and correlation with gene expression suggest that this SNP may affect expression of SMG7 in T cells. CONCLUSIONS: The SNP rs2702185 at the SMG7 locus is associated with time from biochemical recurrence to prostate cancer death, and its LD partner rs10737246 is predicted to be functional. IMPACT: These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.

Epigenetic loss of heterogeneity from low to high grade localized prostate tumours.

Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequence the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumours. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumours. Despite this loss, high-grade tumours exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory programme. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumours. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumours, critical for molecular stratification of the disease.

Survival outcomes and practice trends for off-label use of adjuvant targeted therapy in high-risk locoregional renal cell carcinoma.

IMPORTANCE: The appropriate use of adjuvant targeted therapy (TT) for high-risk locoregional renal cell carcinoma (RCC) after nephrectomy is currently unclear due to mixed results from the relevant randomized controlled trials. National-level survival outcomes and practice trends for the use of adjuvant TT in the United States have not been reported. OBJECTIVE: To compare overall survival for patients who did and did not receive adjuvant TT after nephrectomy for high-risk locoregional RCC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study reviewed the National Cancer Database from 2006 to 2015. Patients with nonmetastatic clear cell RCC who underwent nephrectomy with either stage pT3a or greater or pN+ were included. MAIN OUTCOMES AND MEASURES: Adjuvant TT was defined as receipt of TT within 3 months of nephrectomy. The primary end point was overall survival from initial diagnosis to date of death or censored at last follow-up. Baseline characteristics were described, and a multivariable analysis identified associations for receipt of adjuvant TT. Nearest-neighbor propensity matching was performed to create similar groups for comparison. A survival analysis was performed using Kaplan-Meier analysis and log-rank test. RESULTS: The final study population included 41,127 patients. Two thousand seventy-one patients (5.04%) received off-label adjuvant TT. Younger age, white race, private insurance, positive margins, pT4, and pN+ were associated with receipt of adjuvant TT. After nearest-neighbor propensity matching for clinically and statistically relevant covariates, 1,604 patients remained in the matched cohort, with statistically nonsignificant differences between the groups for all baseline characteristics. Median overall survival was 52 months for patients in the Adjuvant TT group versus 79 months for those who did not receive adjuvant TT (P < 0.001). Decreased overall survival for patients receiving adjuvant therapy was also seen in pathologic subgroups with and without lymph node involvement. CONCLUSIONS: The propensity matched survival analysis revealed significantly decreased overall survival in patients who received off-label adjuvant TT for high-risk locoregional RCC.

The estimated prevalence of missed positive lymph nodes based on extent of lymphadenectomy at radical prostatectomy.

PURPOSE: To determine practice patterns for the extent of lymphadenectomy at radical prostatectomy and associations with detection of pN1 prostate cancer, as well as the impact of lymphadenectomy extent on underdetection of pN1 disease and overall survival. MATERIALS AND METHODS: Prostatectomy cases in the NCDB from 2004 to 2013 were included. Lymphadenectomy extent was defined by the number of nodes examined. Logistic regression was used to identify risk factors for the top quartile of lymph node count and pN1 disease. This model was created to estimate the expected prevalence of pN1, and generated observed over expected ratios. A Cox regression model was used to evaluate the effect of lymph node count on overall survival. RESULTS: Lymphadenectomy was performed in 209,789 (60%) of 358,522 surgeries, with pN1 in 6,428 (3.08%). Increasing quartiles for lymph node count was associated with pN1 (3-5 nodes OR 2.11; 6-8 nodes OR 3.12; ≥9 nodes OR 5.91, all P< 0.001). The logistic regression model suggested that 59% of pN1 cases are missed due to low lymph node count. Increased lymph node count was associated with increasing pN1 detection (O/E: 1-2 nodes = 0.18; 3-5 nodes = 0.37; 6-8 nodes = 0.56; ≥9 nodes = 1.01). Cox proportional hazards modeling demonstrated that the top quartile for lymph node count had improved overall survival (HR 0.93, CI 0.87-0.99, P= 0.03). CONCLUSIONS: Increasing lymphadenectomy extent was associated with pN1 disease on multivariate analysis, and logistic regression modeling suggested a substantial proportion of pN1 were missed due to low lymphadenectomy extent across all risk groups.

Optimizing the Sequence of Chemotherapy for Upper Tract Urothelial Carcinoma with Clinically Positive Regional Lymph Nodes.

PURPOSE: Upper tract urothelial carcinoma with clinically positive regional lymph nodes is an aggressive disease state with a high propensity for metastasis and death. The current literature is limited regarding national practice patterns and outcomes in this patient population. MATERIALS AND METHODS: We identified 1,658 patients in the NCDB (National Cancer Database) who had cN+M0 upper tract urothelial carcinoma. Patients were stratified into treatment groups. We compared baseline patient and tumor characteristics between the groups, and completed survival analysis using a multivariate Cox regression model. RESULTS: There were 1,658 patients in the final study population. Preoperative chemotherapy was the least performed treatment. That group comprised 6.8% of the overall population and was associated with the highest median overall survival of 36 months compared to 21 months for adjuvant chemotherapy, 14 for chemotherapy only, 10 for surgery without perioperative chemotherapy and 5 for no treatment. On multivariate analysis preoperative chemotherapy was associated with improved median overall survival compared to that in the adjuvant chemotherapy group (HR 0.58, 95% CI 0.38-0.87). There was no statistically significant difference in survival between the chemotherapy only and the surgery only groups. Of patients in the preoperative chemotherapy group 34.6% achieved pN0 status compared to 10.3% of those who underwent surgery as initial therapy. CONCLUSIONS: Preoperative chemotherapy was the least performed treatment strategy in the management of cN+M0 upper tract urothelial carcinoma but it was associated with the highest median overall survival. There was no difference in survival between the chemotherapy only and the surgery only groups. Overall these results suggest that initial chemotherapy is appropriate in this population when feasible.

Unconventional Bladder Preservation: Factors Predicting Failure to Receive Definitive Surgery following Chemotherapy for Nonmetastatic Muscle Invasive Bladder Cancer in the National Cancer Database.

PURPOSE: Neoadjuvant chemotherapy is an important adjunct to cystectomy for managing muscle invasive bladder cancer. Using the National Cancer Database we investigated factors that predict failure to undergo surgery following multi-agent chemotherapy for nonmetastatic muscle invasive bladder cancer. MATERIALS AND METHODS: We performed a cohort study in patients diagnosed with cT2-4aN0M0 urothelial cell carcinoma of the bladder between 2004 and 2013 who underwent multi-agent chemotherapy. We excluded those with surgery prior to chemotherapy, clinical T4b disease and those who received radiotherapy. Socioeconomic and clinical predictors, including time from diagnosis to treatment, were analyzed using logistic regression for the receipt of surgery after chemotherapy. Cox proportional hazards modeling was applied to perform time dependent analysis. RESULTS: Of the 4,640 patients who met our study inclusion and exclusion criteria 4,244 (91%) proceeded to surgery. Negative predictors of surgery included African American or Hispanic race (OR 0.58, p = 0.007 and 0.48, p = 0.002, respectively), increasing age (OR 0.44, p <0.001) and greater time between diagnosis and chemotherapy initiation (fourth quartile greater than 59 days, OR 0.51, p <0.001). African American race (HR 0.79, p <0.001), Medicare (HR 0.86, p <0.001) and other government insurance (HR 0.73, p <0.001) were associated with delayed chemotherapy. CONCLUSIONS: Increasing age, African American or Hispanic race and longer time to chemotherapy predicted failure to undergo surgery. Furthermore, African American race was associated with delayed chemotherapy. Chemotherapy was also delayed in patients on Medicare or other government insurance. Longer time to neoadjuvant chemotherapy is a modifiable risk factor that should be closely observed in multimodal cancer treatment.

Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma.

BACKGROUND: Patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) resulting from fumarate hydratase (FH) mutations may present with skin, uterine, and renal tumors, with each having unique pathologic features. This study investigated the association between prospectively identified suspicious pathology (SP) and FH mutations when patients were referred for genetic testing. METHODS: This was an institutional review board-approved cohort study of patients receiving FH testing from 2008 to 2013. SP was defined as a report of HLRCC histologic features identified during a prospective pathologic assessment. The association between SP and FH mutations was analyzed. RESULTS: FH testing was performed in 29 patients with a median age of 37 years; 15 (52%) were female, and 18 (62%) were white. Pathologists reported SP from kidney tumors (11 of 18), leiomyomas (9 of 15: uterus [n = 8] and bladder [n = 1]), and metastatic tumors (3 of 6) in 23 of 39 associated specimens (59%) from 21 of the 29 patients (72%). Patients with SP were younger (35 vs 51 years; P = .010), and those with kidney tumors more often had stage pT3 or higher renal cell carcinoma than those without SP (100% vs 33%; P = .006). FH mutations were present in 8 patients with SP (38%) and in 1 patient without SP (13%; P = .37); 7 of these patients had kidney cancer (n for SP = 7), all with N1 disease. Analyzing SP by tissue type identified only SP from renal tumors as being significantly associated with positive testing for an FH mutation (P = .013). CONCLUSIONS: SP from kidney tumors was statistically associated with FH mutations. An expert pathologic assessment of renal tumors will facilitate the clinical identification of HLRCC cases, and this will result in genetic testing and targeted cancer screening for patients and at-risk family members. Cancer 2017;123:2452-58. © 2017 American Cancer Society.

Bilateral Testicular Germ Cell Tumors in the Era of Multimodal Therapy.

OBJECTIVE: To characterize the incidence, presentation, management, and relapse of a large population of bilateral testicular germ cell tumors (TGCT) from a single institution. PATIENTS AND METHODS: We identified bilateral TGCT diagnosed between January 1989 and February 2014. We categorized synchronous and metachronous TGCT, noting time between first and second TGCT, histology (seminoma vs nonseminoma [NSGCT]), stage, and treatments. Kaplan-Meier survival estimates characterized relapse. RESULTS: Of 5132 patients with TGCT, 128 (2.5%) had bilateral TGCT. Bilateral TGCT increased over time-1.7% in 1989-1994 up to 3.8% in 2010 to February 2014. The 35 (27%) synchronous cases of TGCT had 20 (57%) concordant seminoma, 5 (14%) concordant NSGCT, and 10 (29%) discordant NSGCT. The 93 (73%) metachronous cases had median time interval to second TGCT of 73 months (range: 5 months-28.6 years). Compared with first TGCT, 39 (42%) had discordant histology, 29 (31%) had concordant seminoma, and 25 (27%) had concordant NSGCT. Stage at first tumor was statistically similar to second TGCT (second stage I, II, II in 69%, 22%, 10%). Increasing duration between first and second TGCT was not associated with higher stage (II or III) at second TGCT (P = .09). Treatment at first tumor was not associated with stage at second tumor. Relapse following bilateral diagnosis was 16.8% (95% confidence interval 10.5%-26.2%) at 5 years. CONCLUSION: Incidence of bilateral TGCT increased with >25% of metachronous TGCT presenting ≥10 years after first TGCT; possible causes include increased survivorship and referral bias. Stage was statistically similar at first and second tumor; stage at second tumor was not associated with time interval between tumors or prior treatment modality at first tumor.

Association of rise in C-reactive protein with decline in renal function following partial nephrectomy.

INTRODUCTION: To investigate association of C-reactive protein (CRP), a marker of systemic inflammation, with renal functional decline patients undergoing partial nephrectomy (PN) for renal mass. MATERIALS AND METHODS: Retrospective study of patients who underwent PN between February 2006-March 2011, with ≥ 6 months follow up. Data was analyzed between two groups: CRP increase ≥ 0.5 mg/L from 6 months postoperative ('CRP rise,' CRPR), versus no CRP increase = 0.5 ('CRP stable,' CRPS). Primary outcome was change in estimated glomerular filtration rate (ΔeGFR, mL/min/1.73 m²), with de novo postoperative stage III chronic kidney disease (stage III-CKD, eGFR < 60 mL/min/1.73 m²) being secondary. Multivariable analysis (MVA) was conducted to identify risk factors for development of de novo stage III-CKD. RESULTS: A total of 243 patients (206 CRPS/37 CRPR) were analyzed. Demographics and R.E.N.A.L. nephrometry scores were similar. CRPR had significantly higher median ΔeGFR (-13.7 versus -32.0 mL/min/1.73 m², p < 0.001) and de novo stage III-CKD at last follow up (43.2% vs. 3.7%, p < 0.001). Median time to CRP rise was 10 (IQR 6.5-12) months. Median time from CRP rise to de novo stage III-CKD was 9 (IQR 7.5-11) months. MVA found RENAL score (OR 1.89, p = 0.001), hypertension (OR 4.75, p = 0.016), and CRP rise (OR 55.76, p < 0.001) were associated with de novo stage III-CKD. Sensitivity of CRP increase ≥ 0.5 for predicting CKD was 69.6%, specificity 93.3%, positive predictive value 55.2%, and negative predictive value 96.3%. CONCLUSION: Rise in CRP postoperatively is independently associated with renal functional decline after PN and may be useful in identifying patients to evaluate for renoprotective strategies. Further studies are requisite to clarify etiology of this association.

Analysis of Renal Functional Outcomes After Radical or Partial Nephrectomy for Renal Masses ≥7 cm Using the RENAL Score.

OBJECTIVE: To determine if partial nephrectomy (PN) confers a renal functional benefit compared to radical nephrectomy (RN) for clinical T2 renal masses (T2RM) when adjusting for tumor complexity characterized by the RENAL nephrometry score. METHODS: A 2-center study of 202 patients with T2RM undergoing RN (122) or PN (80) (median follow-up, 41.5 months). RN and PN cohorts were subanalyzed according to RENAL sum as a categorical variable of <10 or ≥10. Primary outcome was median change in estimated glomerular filtration rate (ΔeGFR) between preoperative to 6 months postoperative. Logistic regression-identified prognostic factors and survival models analyzed association between the RENAL sum and the freedom from de novo chronic kidney disease (CKD; eGFR<60 mL/min/1.73m(2)). RESULTS: No significant differences existed between PN and RN for RENAL score. ΔeGFR was greater in RN (-19.7) vs PN (-11.9; P = .006). De novo CKD was 40.2% after RN vs 16.3% after PN (P <.001). RENAL score ≥10 (odds ratio, 6.67; P = .025) and RN among patients with RENAL score <10 (odds ratio, 24.8; P <.001) were independently associated with de novo CKD at 6 months by logistic regression. Among patients with RENAL score <10, median CKD-free survival was PN 38 vs RN 16 months (P = .001). Cox proportional hazard demonstrated decreasing risk of CKD for PN vs RN from RENAL 10 (hazard ratio, 0.836) to RENAL 6 (hazard ratio, 0.003; P = .001). CONCLUSION: RN is independently associated with decreased renal function compared to PN for T2RM with RENAL sum ≤10, but not >10, with larger relative decrease in eGFR for each decrease in RENAL sum. Further investigation is required to determine optimal candidates for PN in T2RM.

Impact of renal surgery for cortical neoplasms on lipid metabolism.

OBJECTIVE: To examine the incidence of and risk factors for development of hyperlipidaemia in patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) for renal cortical neoplasms, as hyperlipidaemia is a major source of morbidity in chronic kidney disease (CKD). PATIENTS AND METHODS: We conducted a two-centre retrospective analysis of 905 patients (mean age 57.5 years, mean follow-up 78 months), who underwent RN (n = 610) or PN (n = 295) between July 1987 and June 2007. Demographics, preoperative and postoperative hyperlipidaemia were recorded. De novo hyperlipidaemia was defined as that ocurring ≥6 months after surgery in cases where laboratory values met National Cholesterol Education Program Adult Treatment Panel III definitions. The Kaplan-Meier method was used to assess freedom from de novo hyperlipidaemia. Multivariable analysis was conducted to determine the risk factors for de novo hyperlipidaemia. RESULTS: There were no significant differences with respect to demographics, preoperative glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (P = 0.123) and hyperlipidaemia (P = 0.144). Tumour size (cm) was significantly larger in the RN group vs the PN group (7.0 vs 3.7; P < 0.001). Significantly greater postoperative GFR <60 mL/min/1.73 m(2) was noted in the RN group (45.7 vs 18%, P < 0.001). Significantly, more de novo hyperlipidaemia developed in the RN group than in the PN group (23 vs 6.4%; P < 0.001). The mean time to development of hyperlipidaemia was longer for PN than for RN (54 vs 44 months; P = 0.03). Five-year freedom from de novo hyperlipidaemia probability was 76% for RN vs 96% for PN (P < 0.001). Multivariable analysis showed that RN (odds ratio [OR] 2.93; P = 0.0107), preoperative GFR <60 mL/min/1.73 m(2) (OR 1.98; P = 0.037) and postoperative GFR <60 mL/min/1.73 m(2) (OR 7.89; P < 0.001) were factors associated with hyperlipidaemia development. CONCLUSION: Patients who underwent RN had a significantly higher incidence of and shorter time to development of de novo hyperlipidaemia. RN and pre- and postoperative eGFR <60 mL/min/1.73 m(2) were associated with development of hyperlipidaemia. Further follow-up and prospective investigation are necessary to confirm these findings.

Determinants of renal functional decline after open partial nephrectomy: a comparison of warm, cold, and non-ischemic modalities.

INTRODUCTION: Renal functional decline after partial nephrectomy (PN) may be related to a variety of nonmodifiable and modifiable factors, including ischemia time (IT) and modality. We sought to determine the impact of these factors on renal functional degeneration after PN. MATERIALS AND METHODS: Multicenter retrospective analysis (n = 347) was performed, identifying patients who underwent open PN using warm, cold, and non-ischemic techniques. Primary outcome was development of de novo chronic kidney disease (CKD), (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2), at 1 year follow up. Univariate and multivariable analysis (MVA) were performed examining factors associated with ischemia technique and the development of de novo CKD. RESULTS: Median follow up 34.7 months. Two hundred and forty-one patients underwent warm ischemic, 31 cold ischemic, and 75 clampless PN. Patient characteristics were similar between groups. Clampless group had lower mean RENAL scores (6.4) than cold (7.9, p = 0.005) and warm (7, p = 0.037) ischemia groups. Cold ischemia cohort had longer median IT than the warm cohort (50min versus 25 min, p = 0.001). There were no significant differences in proportion of patients developing de novo CKD (warm 14.9%, cold 15%, clampless 8.7%, p = 0.422). MVA demonstrated that neither ischemic modality nor IT ≥ 30 minutes was associated with development of de novo CKD, while RENAL scores of increasing complexity (RENAL score 7-9 OR 4.32, p = 0.003; RENAL score ≥ 10 OR 15.42, p < 0.001) were independently associated with de novo CKD. CONCLUSIONS: Increasing tumor complexity, as indicated by the RENAL score, was an overriding determinant of post PN renal functional outcome. Prospective investigation is requisite to elucidate risk and protective factors for renal functional degeneration after PN.

Survival outcomes after radical and partial nephrectomy for clinical T2 renal tumours categorised by R.E.N.A.L. nephrometry score.

OBJECTIVE: We evaluated survival outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for clinical T2 renal masses (cT2RM) controlling for R.E.N.A.L. nephrometry score. PATIENTS AND METHODS: A two-centre study comprised of 202 patients with cT2RM who underwent RN (122) or PN (80) between July 2002 and June 2012 (median follow-up 41.5 months). Kaplan-Meier analysis compared overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) among the entire cohort and within categories of R.E.N.A.L. nephrometry score of ≥10 and <10. Association between procedure and PFS and OS was analysed using Cox-proportional hazard. RESULTS: There were no significant differences between PN and RN in clinical T stage and R.E.N.A.L. nephrometry scores. For RN and PN, the 5-year PFS was 69.8% and 79.9% (P = 0.115), CSS was 82.5% and 86.7% (P = 0.407), and OS was 80% and 83.3% (P = 0.291). Cox regression showed no association between RN vs PN and PFS; a R.E.N.A.L. nephrometry score of ≥10 was associated with a shorter PFS (hazard ratio 6.69, P = 0.002). Kaplan-Meier analysis for RN vs PN showed no difference in PFS for entire cohort or within the R.E.N.A.L. nephrometry score categories of ≥10 and <10. The PFS was better for those with R.E.N.A.L nephrometry scores of <10 vs ≥10 (P < 0.001) and for cT2a vs cT2b tumours (P = 0.012). OS was no different between cT2a and cT2b tumours; patients with R.E.N.A.L. nephrometry scores of ≥10 were more likely to die from disease (P < 0.001) or any cause (P < 0.001) vs those with R.E.N.A.L. nephrometry scores of <10. CONCLUSIONS: PN may be oncologically effective for cT2RM. A R.E.N.A.L nephrometry score of ≥10 is negatively associated with OS among cT2RM compared with a score of <10 and provides additional risk assessment beyond clinical T stage. Further follow-up and prospective randomised investigation is requisite to confirm efficacy of PN for cT2RM.

Partial Cystectomy after Neoadjuvant Chemotherapy: Memorial Sloan Kettering Cancer Center Contemporary Experience.

Objective. To report our contemporary experience with partial cystectomy after neoadjuvant chemotherapy. Patients and Methods. Retrospective review of patients who underwent neoadjuvant chemotherapy and partial cystectomy for urothelial cell carcinoma of the bladder at Memorial Sloan Kettering Cancer Center from 1995 to 2013. Log-rank test and Cox regression models were used to analyze variables possibly associated with recurrence-free, advanced recurrence-free (free from recurrence beyond salvage with intravesical therapy or radical cystectomy), and overall survival. Results. All 36 patients had a solitary tumor <5 cm in size. Twenty-one patients (58%) achieved cT0 following neoadjuvant chemotherapy with 7 (33%) having residual disease at PC. At last follow-up, 19 (53%) patients had recurrence, 15 (42%) had advanced recurrence, 10 (28%) died of disease, and 22 (61%) maintained an intact bladder. Median follow-up of those who were with no evidence of disease was 17 months. On univariable analysis, after neoadjuvant chemotherapy positive nodes on imaging and positive surgical margin at partial cystectomy were both associated with worse recurrence-free, advanced recurrence-free, and overall survival. Five-year recurrence-free, advanced recurrence-free, and overall survival were 28%, 51%, and 63%, respectively. Conclusion. Partial cystectomy following neoadjuvant chemotherapy provides acceptable oncologic outcomes in highly selected patients with muscle-invasive bladder cancer.