Pathological characteristics of the large renal mass: potential implication for clinical role of renal biopsy.

INTRODUCTION: To assess whether patients with a large renal mass, treated by radical nephrectomy (RN), could have benefited from preoperative renal mass biopsy (RMB). The decision to perform partial nephrectomy (PN) for an organ-confined > 4 cm renal mass can be complex. Albeit often feasible, oncologic safety of PN in this cohort is debated. Yet, a significant portion of large renal masses that undergo RN prove benign or indolent, indicating a potential role for RMB to guide nephron preservation. MATERIALS AND METHODS: We queried prospectively maintained databases from three institutions to identify patients who underwent RN for localized > 4 cm renal mass. We excluded patients with nodal or distant metastases. Multivariable analysis assessed how clinicopathologic variables, mass anatomic complexity, and patient comorbidities related to the likelihood of harboring an indolent neoplasm. RESULTS: A total of 702 patients underwent RN for localized > 4 cm renal mass (median tumor size 7.0 cm (IQR 5.5-9.2); 12.8% (n = 90) of patients were diagnosed with oncocytoma/oncocytic neoplasm (n = 27, 3.8%) or chromophobe RCC (n = 63, 9.0%). When stratified by tumor size, indolent tumors comprised 10.1% of 4-7 cm masses, 15.6% of ≥ 7-10 cm masses, and 17.3% of ≥ 10 cm tumors. Upon multivariate analysis, younger age was associated with indolent tumors (p = 0.04, OR 0.97, 95% CI 0.94-0.99). CONCLUSIONS: Approximately 1 in 8 patients with a renal mass > 4 cm harbored benign or low risk indolent potential lesions and were associated with younger age. As such, patients with large renal masses for whom risk trade-offs between PN and RN are unclear, present a unique opportunity for greater utilization of RMB.

The current role of cytoreductive nephrectomy for metastatic renal cell carcinoma.

The management of metastatic renal cell carcinoma (mRCC) continues to be a therapeutic challenge; however, the options for systemic therapy in this setting have exploded over the past 20 years. From the advent of toxic cytokine therapy to the subsequent discovery of targeted therapy (TT) and immune checkpoint inhibitors, the landscape of viable treatment options continues to progress. With the arrival of cytokine therapy, two randomized trials demonstrated a survival benefit for upfront cytoreductive nephrectomy (CN) plus interferon therapy and this approach became the standard for surgical candidates. However, it was difficult to establish the role and the timing of CN with the subsequent advent of TT, just a few years later. More recently, two randomized phase III studies completed in the TT era questioned the use of CN and brought to light the role of risk stratification while selecting patients for CN. Careful identification of the mRCC patients who are likely to have a rapid progression of the disease is essential, as these patients need prompt systemic therapy. With the continued advancement of systemic therapy using the immune checkpoint inhibitors as a first line therapy, the role of CN will continue to evolve.

Optimizing patient selection for cytoreductive nephrectomy based on outcomes in the contemporary era of systemic therapy.

BACKGROUND: The management of metastatic renal cell carcinoma (mRCC) has evolved rapidly, and results from the Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) trial bring into question the utility of cytoreductive nephrectomy (CN). The objective of this study was to examine overall survival (OS) and identify risk factors associated with patients less likely to benefit from CN in the targeted therapy era. METHODS: Patients with mRCC undergoing CN from 2005 to 2017 were identified. Kaplan-Meier methods and Cox proportional hazards regression analyses were used to assess OS and risk-stratify patients, respectively, on the basis of preoperative clinical and laboratory data. RESULTS: Six hundred eight patients were eligible with a median follow-up of 29.4 months. Ninety-five percent of the patients had an Eastern Cooperative Oncology Group performance status less than or equal to 1, and 70% had a single site of metastatic disease. In a multivariable analysis, risk factors significantly associated with decreased OS included systemic symptoms at diagnosis, retroperitoneal and supradiaphragmatic lymphadenopathy, bone metastasis, clinical T4 disease, a hemoglobin level less than the lower limit of normal (LLN), a serum albumin level less than the LLN, a serum lactate dehydrogenase level greater than the upper limit of normal, and a neutrophil/lymphocyte ratio greater than or equal to 4. Patients were stratified into 3 risk groups: low (fewer than 2 risk factors), intermediate (2-3 risk factors), and high (more than 3 risk factors). These groups had median OS of 58.9 months (95% confidence interval [CI], 44.3-66.6 months), 30.6 months (95% CI, 27.0-35.0 months), and 19.2 months (95% CI, 13.9-22.6 months), respectively (P < .0001). The median time to postoperative systemic therapy was 45 days (interquartile range, 30-90 days). CONCLUSIONS: Patients with more than 3 risk factors did not seem to benefit from CN. Importantly, OS in this group was equivalent to, if not higher than, OS for patients in the CN plus sunitinib arm of CARMENA, and this raises the possibility that a well-selected population might benefit from CN.

Intraoperative and early postoperative complications in postchemotherapy retroperitoneal lymphadenectomy among patients with germ cell tumors using validated grading classifications.

BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.

Prediction of significant estimated glomerular filtration rate decline after renal unit removal to aid in the clinical choice between radical and partial nephrectomy in patients with a renal mass and normal renal function.

OBJECTIVES: To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m2 after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN). PATIENTS AND METHODS: Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m2 who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit. RESULTS: A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m2 . On multivariable analysis, increasing age (P = 0.001), female gender (P < 0.001), and increasing preoperative creatinine level (P < 0.001) were associated with functional decline. We constructed a predictive nomogram that included these variables in addition to comorbidities with a known association with kidney disease, but found that a simplified model excluding comorbidities was equally robust (cross-validated area under the ROC curve was 0.78). Decision-curve analysis showed the net clinical benefit at probabilities >~11%. CONCLUSIONS: The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m2 , who may be stronger candidates for nephron preservation.

Quality of life assessment among ethnically diverse Black prostate cancer survivors: a constructivist grounded theory approach.

PURPOSE: Prostate cancer (CaP) is the most common cancer in Black men (BM), and the number of Black CaP survivors is rapidly increasing. Although Black immigrants are among the fastest-growing and most heterogeneous ethnic groups in the USA, limited data exist regarding their CaP experiences. Therefore, this study aimed to explore and model the experiences of ethnically diverse Black men with CaP. METHODS: In-depth interviews were conducted with 34 participants: native-born BM (NBBM) (n = 17), African-born BM (ABBM) (n = 11), and Caribbean-born BM (CBBM) (n = 6) CaP survivors recruited through QR code-embedded flyers posted in Black businesses, clinics, social media platforms, and existing research networks within the USA. Guided by Charmaz's constructivist grounded theory methodology, the interviews were analyzed using constant comparison following key stages of initial, focused, and theoretical coding using Atlas.ti v23. RESULTS: Participants were thirty-four men aged 49-84 years (mean ± SD, 66 ± 8). Most were married (77%), likely to be diagnosed at stage I (35%), and treated with radiotherapy (56%). Our study findings explored the complex trajectory of Black prostate cancer (CaP) survivors, unveiling a comprehensive model termed "Journeying through Unfamiliar Terrain." Comprising three phases and 11 sub-phases, this model uniquely captures the pre-diagnosis awareness and post-treatment adaptation among survivors. CONCLUSION: The resulting theoretical model delineates the entire CaP survivorship process among BM, providing contextual and conceptual understanding for developing interventions and enhancing patient-centered care for ethnically diverse CaP survivors, pivotal in bridging the gaps in survivorship research and healthcare practices. IMPLICATIONS FOR CANCER SURVIVORS: Black CAP survivors experience significant burdens and challenges that impact their overall quality of life. Understanding the factors that impact the complex survivorship journey can inform design and implementation of interventions to address the multiple challenges and thus improve quality of life.

Kidney Cancer Incidence and Mortality Disparities Involving American Indians/Alaska Natives: An Analysis of the Oklahoma Central Cancer Registry (OCCR).

Purpose: This cohort study describes the differences in kidney cancer age-adjusted incidence and mortality rates between American Indians/Alaskan Natives (AI/ANs) and Whites in Oklahoma. Additionally, rates for the U.S. are updated to establish an epidemiological comparison between Oklahoma and the rest of the country. Materials and Methods: Kidney cancer age-adjusted incidence and mortality rates for Oklahoma were gathered using the Oklahoma Central Cancer Registry since 1999. National rates were obtained from the Center for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database between 1997 and 2017. Rate ratios were used to compare incidence and mortality rates for AI/ANs and Whites within Oklahoma as well as the entire country. Joinpoint regression models were created to illustrate trends in kidney cancer incidence and mortality. Results: The age-adjusted incidence rate of kidney cancer in Oklahoma for AI/ANs and Whites was 32.3 and 15.8 per 100,000, respectively, for an incidence rate ratio of 2.04. The national incidence rate ratio was 0.89. The age-adjusted mortality rate in Oklahoma for AI/ANs and Whites was 9.78 and 4.98 per 100,000, respectively, for a mortality rate ratio of 1.98. Oklahomans, irrespective of race, fare worse in terms of kidney cancer mortality compared to the rest of the country. Conclusions: In Oklahoma, AI/ANs are more likely than Whites to have a kidney cancer diagnosis. AI/ANs are twice as likely to die from kidney cancer than Whites in Oklahoma. AI/AN populations in certain states may benefit from kidney cancer early screening initiatives.

Role of lymph node dissection at the time of open or minimally invasive nephroureterectomy.

Unlike urothelial carcinoma of the bladder, there is no guideline-based consensus on whether a lymph node dissection (LND) should be performed at the time of radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Variable lymphatic drainage based on primary tumor location, lack of prospective trials, and difficulties in developing a risk-adapted approach to LND for UTUC are all challenges to the development of an established approach. The UTUC literature consists of an evidence pool that has historically been limited to single-institution series with heterogenous inclusion criteria for LND and variable LND templates. Areas of controversy exist regarding migration to the great vessel LN beds for mid and distal tumors. A lack of template standardization limits the interpretation of studies relative to one another and a lack of uniformity in reporting templates may lead to inaccuracies in the estimation of lymph node metastasis landing sites. Most clinicians agree that there is a staging benefit to LND for UTUC. Although the data is somewhat heterogenous, it demonstrates a prognostic and staging benefit to LND in higher stages of UTUC. Unlike the staging benefits provided by LND for UTUC, the therapeutic benefits are not as clearly established. Several studies have evaluated differences in cancer-specific survival (CSS) and demonstrated LND to be an independent predictor of CSS when compared to patients not undergoing LND. However, this finding is not consistent across all studies and the literature is again limited by inclusion heterogeneity and inconsistent or lack or template-based resections. LND for UTUC at the time of RNU is a safe and feasible procedure that seems to especially benefit patients with muscle-invasive or locally advanced disease. Prospective, randomized studies with strict inclusion criteria and defined anatomic templates are needed to definitely characterize the role of LND for UTUC.

Does a screening digital rectal exam provide actionable clinical utility in patients with an elevated PSA and positive MRI?

Objective: To define the value of a digital rectal exam (DRE) in the prostate-magnetic resonance imaging (MRI) era. Prostate MRI is increasingly used in men with elevated prostate-specific antigen (PSA) prior to biopsy. Methods: A retrospective study was performed in men with elevated PSA undergoing MRI followed by MRI fusion with systematic biopsy and men with elevated PSA/active surveillance with negative MRI followed by biopsy. Baseline clinicopathologic characteristics and DRE findings were collected. We examined performance of a positive DRE on sensitivity and specificity of diagnosing clinically significant prostate cancer (CSPC). Results: A total of 339 patients had elevated PSA and positive MRI followed by MRI fusion guided with systematic biopsy. Pre-biopsy DRE was documented in 286/339 patients, who were included in further analysis. About 81.6% positive, 78.7% questionable, and 55.8% negative DRE patients had CSPC. Positive DRE had 21.8% sensitivity and 91.3% specificity for CSPC. Positive or questionable DRE had 42.1% sensitivity and 81.5% specificity. Among 148 men with non-CSPC (GG1)-targeted biopsy, 28 had systematic biopsy with CSPC. About 5/28 had positive DRE and 8/28 had positive or questionable DRE. Twenty-seven patients were included who had elevated PSA/on active surveillance with negative MRI and biopsy done within 2 years. About 77.8% had negative, 7.4% had questionable, and 14.8% men had positive DRE. About 7.4% had CSPC and all had a negative DRE. Conclusions: Our study provides limited evidence for the value of a DRE. However, it does show occasional benefit in detecting GG2 or higher disease and given the lack of cost and side effects, should still be considered.

Active Surveillance for Localized Renal Masses: Tumor Growth, Delayed Intervention Rates, and >5-yr Clinical Outcomes.

BACKGROUND: Active surveillance (AS) has gained acceptance as a management strategy for localized renal masses. OBJECTIVE: To review our large single-center experience with AS. DESIGN, SETTING, AND PARTICIPANTS: From 2000 to 2016, we identified 457 patients with 544 lesions managed with AS from our prospectively maintained kidney cancer database. A subset analysis was performed for patients with ≥5-yr follow-up without delayed intervention (DI). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Linear growth rates (LGRs) were estimated using linear regression for the initial LGR (iLGR) AS interval and the entire AS period. Overall survival (OS) and cumulative incidence of DI were estimated with Kaplan-Meier methods utilizing iLGR groups, adjusting for covariates. DI was evaluated for association with OS in Cox models. RESULTS AND LIMITATIONS: Median follow-up was 67 mo (interquartile range [IQR] 41-94 mo) for surviving patients. Cumulative incidence of DI (n=153) after 1, 2, 3, 4, and 5 yr was 9%, 22%, 29%, 35%, and 42%, respectively. Median initial maximum tumor dimension was 2.1cm (IQR 1.5-3.1cm). Median iLGR and overall LGR were 1.9 (IQR 0-7) and 1.9 (IQR 0.3-4.2) mm/yr, respectively. Compared with the no growth group, low iLGR (hazard ratio [HR] 1.25, 95% cumulative incidence [CI] 0.82-1.91), moderate iLGR (HR 2.1, 95% CI 1.31-3.36), and high iLGR (HR 1.87, 95% CI 1.23-2.84) were associated with DI (p=0.003). The iLGR was not associated with OS (p=0.8). DI was not associated with OS (HR 1.34, 95% CI 0.79-2.29, p=0.3). Five-year cancer-specific mortality (CSM) was 1.2% (95% CI 0.4-2.8%). Of 99 patients on AS without DI for >5 yr, one patient metastasized. CONCLUSIONS: At >5 yr, AS±DI is a successful strategy in carefully managed patients. DI often occurs in the first 2-3 yr, becoming less likely over time. Rare metastasis and low CSM rates should reassure physicians that AS is safe in the intermediate to long term. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with kidney masses who elected to enroll in active surveillance rather than immediate surgery. We found that patients who need surgery are often identified early and those who remain on active surveillance become less likely to need surgery over time. We concluded that active surveillance with or without delayed surgery is a safe practice and that, when properly managed and followed, patients are unlikely to metastasize or die from kidney cancer.

WBC Associates with Readmission Following Cystectomy.

Background: Radical cystectomy is associated with perioperative complication rates exceeding 50% in some series. Readmission rates are increasingly used as a surgical quality metric. White blood cell count is a crude surrogate for physiologic processes which may reflect postoperative complications leading to readmission. Objective: We assessed the association between final white blood cell count at discharge and risk of readmission following radical cystectomy. Methods: Records on 477 patients undergoing radical cystectomy from 2006-2013 were reviewed. Final white blood cell count was defined as the last documented value during index admission. Univariate analysis was performed using Fisher's exact, Wilcoxon rank sum test, and Spearman's coefficient tests where appropriate. Multivariable logistic regression models were used to test the associations between final white blood cell count and readmission. Results: 34% of patients were readmitted within 90 days of surgery. Amongst this cohort, a cutoff final white blood cell count of 9000/mm3 was identified, with a significantly higher proportion of patients with values >9000/mm3 experiencing readmission than those with values≤9000/mm3 (42% vs 28%, p = 0.004). Other perioperative variables associated with an increased readmission rate included initial hospital length of stay≤10 days, and receipt of a continent diversion. Following adjustment, final white blood cell count >9000/mm3 was associated with increased risk of readmission (OR 2.09, 95% CI 1.23-3.53, p = 0.006). Conclusions: Final white blood cell count is associated with hospital readmission following radical cystectomy. This metric may provide important guidance in discharge algorithms.

Definition, incidence, risk factors, and prevention of paralytic ileus following radical cystectomy: a systematic review.

CONTEXT: Postoperative paralytic ileus (POI) has profound clinical consequences because it represents a substantial burden on both patients and health care resources. OBJECTIVE: To determine the knowledge base regarding POI in the radical cystectomy (RC) population with an emphasis on preventive measures and risk factors. EVIDENCE ACQUISITION: A systematic literature search of Medline (1966 to February 2011) and a study review were conducted. Eligible studies explicitly reported the incidence of POI and/or at least two quantitative measures of gastrointestinal recovery. EVIDENCE SYNTHESIS: The search identified 727 relevant articles; 77 met eligibility criteria, comprising 13 793 patients. Of these, 21 used explicit definitions of POI, and they varied widely. Across studies, the incidence of POI ranged from 1.58% to 23.5%. Possible risk factors for POI included increasing age and body mass index. Seventeen studies reported effects of an intervention on POI: 3 randomized controlled studies, 11 observational cohort studies with concurrent comparison, and 3 observational cohort studies with nonconcurrent comparison. Gum chewing was associated with shortened times to flatus (2.4 vs 2.9 d; p<0.0001) and bowel movement (BM) (3.2 vs 3.9 d; p<0.001) in one observational cohort study (n=102); omission of a postoperative nasogastric tube (NGT) was associated with shorter time to flatus (4.21 vs 5.33 d; p=0.0001) and shorter length of stay (14.4 vs 19.1 d; p=0.001) in one observational cohort study (n=430); and the routine use of bowel preparation was associated with an increased incidence of POI (5% vs 19%) in another series (n=86). Additionally, readaptation of the dorsolateral peritoneal layer was shown to shorten times to flatus (p=0.016) and times to BM (p=0.011) in one randomized controlled study (n=200). CONCLUSIONS: The incidence/definition of POI after RC is highly variable. An improved reporting strategy is needed to identify true incidence and risk factors, and to guide future research for both potential preventive and therapeutic interventions.