Zachary Hamilton

Neoadjuvant therapy for localized and locally advanced renal cell carcinoma

Neoadjuvant Targeted Molecular Therapy in the setting of localized and locally advanced renal cell carcinoma has emerged as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. Presurgical tumor reduction has been demonstrated in a number of studies including a recently published randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Nonetheless, most reports are small phase II clinical trials or retrospective reports. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for neoadjuvant strategies. This article reviews the current status and future prospects of neoadjuvant therapy in nonmetastatic renal cell carcinoma.

Utilization and quality outcomes of cT1a, cT1b and cT2a partial nephrectomy: analysis of the national cancer database

To describe the utilization and compare quality outcomes of partial nephrectomy (PN) for cT1a, cT1b and cT2a renal masses using a large national database.

Impact of tumor histology and grade on treatment success of percutaneous renal cryoablation.

BackgroundWe analyzed oncological outcomes in patients who underwent percutaneous renal cryoablation (PRC) with documented renal cell carcinoma (RCC) by perioperative biopsy.MethodsMulticenter retrospective analysis of 153 patients [median follow-up 48xa0months] who underwent PRC from 09/2005 to 08/2014 was performed. We divided the cohort into patients who developed recurrence versus no recurrence. Kaplan–Meier analyses examined recurrence-free survival (RFS) according to grade and histology. Multivariable analysis (MVA) was performed to identify factors associated with tumor recurrence.ResultsOne hundred and fifty-three patients were analyzed [18 patients (11.8xa0%) with recurrence and 135 (88.2xa0%) patients without recurrence]. There were no differences between the groups with respect to demographics, RENAL score, and number of probes utilized. Recurrence group had larger tumor size (3.1 vs. 2.4xa0cm; pxa0=xa00.011), upper pole tumor location (pxa0=xa00.016), and greater proportions of high-grade tumor (33 vs. 0.7xa0%; pxa0<xa00.001) and clear cell histology (77.8 vs. 45.9xa0%; pxa0=xa00.011). Four-year RFS was 100 versus 80xa0% for grade 1 versus grade 2/3 tumors (pxa0=xa00.0002), and 97 versus 88xa0% for other RCC versus clear cell RCC (pxa0=xa00.07). MVA demonstrated tumor sizexa0>3xa0cm (OR 2.46; pxa0=xa00.019), clear cell histology (OR 2.12; pxa0=xa00.027), and high tumor grade (OR 2.33, pxa0<xa00.001) as independent risk factors associated with tumor recurrence.ConclusionsAssociation of higher grade and clear cell histology with recurrence and progression suggests need for increased emphasis on preoperative risk stratification by biopsy, with grade 1 and non-clear cell RCC being associated with improved treatment success than higher grade and clear cell RCC.

Perioperative Outcomes Following Partial Nephrectomy Performed on Patients Remaining on Antiplatelet Therapy

Purpose: We evaluated the risk of bleeding complications in patients undergoing partial nephrectomy in whom perioperative antiplatelet therapy was continued, as antiplatelet therapy is increasingly used and hemorrhage is a significant concern in partial nephrectomy. Materials and Methods: In this 2‐center retrospective analysis 1,097 patients underwent partial nephrectomy between 2000 and 2014. The cohort was split into 3 groups of perioperative continuation of antiplatelet therapy (group 1—67), antiplatelet therapy stopped preoperatively (group 2—254) and no chronic antiplatelet therapy (group 3—776). Bleeding complications were defined as any transfusion, or any hospital readmission or secondary procedure performed for hemorrhage. Multivariable analysis was performed to elucidate independent risk factors for bleeding complications. Results: Patients in group 1 were older (median age 66 years vs 64 and 57 years in groups 2/3, p <0.0001), and had greater comorbidity (median ASA classification score 3 vs 2 and 2, p <0.0001). Group 1 had a higher rate of bleeding complications (20.9% vs 7.1% and 6.4%, p <0.0001) and transfusions (16.4% vs 5.9% and 5.4%, p=0.002). Multivariable analysis revealed continued antiplatelet therapy was an independent predictor of bleeding complications (OR 2.19, 95% CI 1.06–4.51, p=0.03). These findings appear attributable to intraoperative clopidogrel use. On multivariable analysis the use of aspirin alone was not associated with bleeding complications (OR 1.64, 95% CI 0.72–3.75, p=0.24). Conclusions: The risk of bleeding complications due to antiplatelet therapy use at partial nephrectomy may be due to clopidogrel. The need to continue perioperative aspirin alone does not appear to be a contraindication to the safe performance of partial nephrectomy.

Comparison of retroperitoneal and transperitoneal robotic partial nephrectomy for Pentafecta perioperative and renal functional outcomes

BackgroundWe compared quality outcomes between transperitoneal (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN).MethodsTwo-center retrospective analysis of TRPN and RRPN from 10/2009 to 10/2015. Perioperative/renal function outcomes were analyzed. Primary endpoint was Pentafecta, a composite measure of quality [negative margin, no 30-day complication, ischemia timexa0≤25xa0min, return of glomerular filtration rate (eGFR) toxa0>90% from baseline at last follow-up, and no chronic kidney disease upstaging]. Multivariable analysis (MVA) for factors associated with lack of optimal outcome was performed.Results404 patients (TRPN 263, RRPN 141) were analyzed. Comparing TRPN vs. RRPN, mean tumor size (3.1 vs. 2.9xa0cm, pxa0=xa00.122) and RENAL score (7.4 vs. 7.2, pxa0=xa00.503) were similar. Most TRPN were anterior (65.0%) and most RRPN posterior (65.3%, pxa0<xa00.001). Operative time (pxa0=xa00.001) was less for RRPN. No significant differences between TRPN vs. RRPN were noted for ischemia time (23.1 vs. 22.8xa0min, pxa0=xa00.313), blood loss (pxa0=xa00.772), positive margins (pxa0=xa00.590), complications (pxa0=xa00.537), length of stay (pxa0=xa00.296), ΔeGFR (pxa0=xa00.246), eGFR recovery toxa0>90% (55.9 vs. 57.4%, pxa0=xa00.833), and lack of CKD upstaging (84.0 vs. 87.2%, pxa0=xa00.464). Pentafecta rates were not significantly different (TRPN 33.9 vs. RRPN 43.3%, pxa0=xa00.526). MVA revealed increasing RENAL score (OR 1.5, pxa0<xa00.001) and decreasing baseline eGFR (OR 2.4, pxa0=xa00.017) as predictive for lack of Pentafecta.ConclusionsTRPN and RRPN have similar quality outcomes, though RRPN may offer modest benefit for operative time and have utility in posterior tumors. Association of increasing RENAL score and decreased baseline eGFR with lack of Pentafecta suggests dominant role of non-modifiable factors.

Analysis of T1 Bladder Cancer on Biopsy and Transurethral Resection Specimens: Comparison and Ranking of T1 Quantification Approaches to Predict Progression to Muscularis Propria Invasion

Urothelial carcinoma of the bladder invasive into lamina propria on biopsy or transurethral resection of bladder tumor, termed “T1” disease, progresses to muscularis propria invasion in a subset of patients. Prior studies have proposed histopathologic metrics to predict progression, although methods vary widely and it is unclear which method is most robust. This poses a challenge since recent World Health Organization and American Joint Commission on Cancer editions encourage some attempt to substratify T1 disease. To address this critical problem, we analyzed T1 specimens to test which T1 quantification method is best to predict progression and to then establish the optimal cut-off. Progression was analyzed for all patients or for patients with definitive muscularis propria only. Multivariate analysis and outcomes modeling controlled for additional histopathologic features. Our results suggest that aggregate linear length of invasive carcinoma (ALLICA) measured by optical micrometer is far superior to other methods (P=3.067×10−6) and could be applied to 100% of specimens. ALLICA retained significance in multivariate analysis and eliminated contribution of other histopathologic features to progression. The best cut-off for ALLICA using a 30% false-positive threshold was 2.3u2009mm and using a 10% false-positive threshold at 25u2009mm, although the latter severely limited patients who could achieve this threshold. After comparison of all proposed methods of T1 quantification, we recommend the adoption of the ALLICA measurement and a cut-off of ≥2.3u2009mm as the best predictor of progression, acknowledging that additional nonhistopathologic methods may be required to increase broad applicability and further reduce the false-positive threshold.

Change in Platelet Count as a Prognostic Indicator for Response to Primary Tyrosine Kinase Inhibitor Therapy in Metastatic Renal Cell Carcinoma

To evaluate change in platelet count as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC).

Chronic Kidney Disease Is More Common in Locally Advanced Renal Cell Carcinoma

OBJECTIVEnTo retrospectively evaluate clinical predictors of chronic kidney disease (CKD) in renal cell carcinoma (RCC) patients to identify associations between patient- and tumor-specific factors with poorer renal function. CKD and RCC are interrelated, with 26%-44% of RCC patients having concomitant CKD at diagnosis.nnnPATIENTS AND METHODSnInstitutional registries from Spectrum Health and University of California, San Diego, were queried for preoperative glomerular filtration rate and proteinuria status before radical or partial nephrectomy. Preoperative clinical and tumor factors were recorded; proteinuria was classified as A1 (<30u2009mg), A2 (30-300u2009mg), and A3 (>300u2009mg). CKD was grouped by Kidney Disease Improving Global Outcomes classification (low, moderately increased, high, very high).nnnRESULTSnWe evaluated 1569 patients undergoing surgery for renal cortical tumors. CKD status was low risk in 860 (55%), moderately increased in 381 (24%), high in 194 (12%), and very high in 134 (9%) patients. Increased radius, exophytic or endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior or posterior, location relative to polar lines score, tumor size, and clinical tumor stage were strongly associated with increased CKD risk at baseline. Clinical stage T3/T4 disease had more at-risk patients than stages T2 and T1 disease (39.5% vs 22% and 19%, Pu2009=u2009.0001). Clinical tumor stage and gender were the only predictors of proteinuria, lower glomerular filtration rate, and higher CKD risk group in both univariate and multivariate analyses.nnnCONCLUSIONnForty-five percent of patients with RCC had moderate or higher CKD before treatment. A positive correlation between pretreatment CKD and locally advanced RCC (cT3/T4) was present. This likely relates to increased loss of functional parenchyma with increasing tumor size or stage, with important implications in patient management.

Change in prostate cancer presentation coinciding with USPSTF screening recommendations at a community-based urology practice

OBJECTIVEnThe benefits of prostate-specific antigen (PSA)-based prostate cancer screening are controversial. We sought to determine the change in prostate cancer presentation coinciding with the release of the United States Preventative Services Task Force recommendations against screening in a high-volume community-based urology practice.nnnMETHODSnCharacteristics of men presenting for an elevated PSA at a community urology practice from August 2011 to August 2015 were queried from a prospectively collected database. A retrospective analysis of presenting PSA, Gleason grade at biopsy, and prostatectomy as well as clinical and pathologic stage was performed. Kruskal-Wallis rank sum and chi-square tests were used for analysis.nnnRESULTSnReferrals for elevated PSA decreased from 933 in year 1 to 816 by year 4 (12.5% decrease) with a concomitant reduction in biopsies performed in newly referred men from 461 to 356 (22.8% decrease, P = 0.02). The proportion of men presenting with PSAs>10 increased from 28.1% to 36.8% (P = 0.009). First-time biopsy-positivity rate increased from 48.4% to 62.4% with a rise in the proportion having Gleason≥7 from 51.6% to 69.7% (P = 0.0001). Of the 578 men who underwent radical prostatectomy, there was a 19.4% increase in Gleason≥7 tumors (P = 0.01).nnnCONCLUSIONSnOur findings demonstrate a decrease in elevated PSA referrals, increase in PSA at the time of referral, decrease in detection of low-risk disease, and increase in detection of intermediate-/high-risk disease in a high-volume, multisite, community-based urology practice, coinciding with the United States Preventative Services Task Force recommendations against PSA screening.

Comparison of functional outcomes of robotic and open partial nephrectomy in patients with pre-existing chronic kidney disease: a multicenter study

BackgroundWe compared renal functional outcomes of robotic (RPN) and open partial nephrectomy (OPN) in patients with chronic kidney disease (CKD), a definite indication for nephron-sparing surgery.MethodsA multicenter retrospective analysis of OPN and RPN in patients with baseline ≥u2009CKD Stage III [estimated glomerular filtration rate (eGFR) <u200960xa0mL/min/1.73xa0m2] was performed. Primary outcome was change in eGFR (ΔeGFR, mL/min/1.73xa0m2) between preoperative and last follow-up with respect to RENAL nephrometry score group [simple (4–6), intermediate (7–9), complex (10–12)]. Secondary outcomes included eGFR decline >u200950%.Results728 patients (426 OPN, 302 RPN, mean follow-up 33.3xa0months) were analyzed. Similar RENAL score distribution (pu2009=u20090.148) was noted between groups. RPN had lower median estimated blood loss (pu2009<u20090.001), and hospital stay (3 vs. 5xa0days, pu2009<u20090.001). Median ischemia time (OPN 23.7 vs. RPN 21.5xa0min, pu2009=u20090.089), positive margin (pu2009=u20090.256), transfusion (pu2009=u20090.166), and 30-day complications (pu2009=u20090.208) were similar. For OPN vs. RPN, mean ΔeGFR demonstrated no significant difference for simple (0.5 vs. 0.3, pu2009=u20090.328), intermediate (2.1 vs. 2.1, pu2009=u20090.384), and complex (4.9 vs. 6.1, pu2009=u20090.108). Cox regression analysis demonstrated that decreasing preoperative eGFR (OR 1.10, pu2009=u20090.001) and complex RENAL score (OR 5.61, pu2009=u20090.03) were independent predictors for eGFR decline >u200950%. Kaplan–Meier analysis demonstrated 5-year freedom from eGFR decline >u200950% of 88.6% for OPN and 88.3% for RPN (pu2009=u20090.724).ConclusionsRPN and OPN demonstrated similar renal functional outcomes when stratified by tumor complexity group. Increasing tumor age and tumor complexity were primary drivers associated with functional decline. RPN provides similar renal functional outcomes to OPN in appropriately selected patients.