Publications by authors named "Robert G Uzzo"

340 Publications

Adjuvant therapy in patients with sarcomatoid renal cell carcinoma: post hoc analysis from Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2805.

BJU Int 2021 Sep 4. Epub 2021 Sep 4.

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

Objectives: To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805.

Patients And Methods: The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805.

Results: A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo).

Conclusions: Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.
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http://dx.doi.org/10.1111/bju.15587DOI Listing
September 2021

Papillary Renal Neoplasm With Reverse Polarity Is Often Cystic: Report of 7 Cases and Review of 93 Cases in the Literature.

Am J Surg Pathol 2021 Aug 5. Epub 2021 Aug 5.

Departments of Pathology Surgical Oncology Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA.

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly proposed entity with distinct histology and frequent KRAS mutations. To date, 93 cases of PRNRPs have been reported. In this study, we present 7 new cases of PRNRP and review the literature. Most of the pathologic features in our 7 cases are similar to those previously reported cases. However, all 7 of our cases showed at least partial cystic changes, which was not stressed in prior studies. Single-nucleotide polymorphism-microarray based chromosomal analysis demonstrated no trisomy or other alteration of chromosomes 7 or 17; and no loss or other alteration of chromosome Y was detected in all 7 cases. Next-generation sequencing detected KRAS missense mutations in 4 of 7 cases. No fusion genes were detected. In summary, PRNRP is a small, well-circumscribed often encapsulated and cystic neoplasm with loose papillary formations. Cuboidal tumor cells always have eosinophilic cytoplasm and nuclei located at the pole opposite the basement membrane with a low World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) nuclear grade. The fibrovascular cores can be hyalinized or edematous. Macrophage aggregates and intracellular hemosiderin are uncommon, and no psammoma bodies or necrosis should be seen. Immunophenotypically, this tumor is always positive for CK7 and GATA3, and negative for CD117 and vimentin. CD10 and AMACR can be positive, but often weakly and focally. PRNRP often has KRAS mutations, however, only 32% of cases have chromosomal abnormalities in chromosomes 7, 17, and Y. No recurrences, metastases, or tumor-related deaths have been reported following complete resection.
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http://dx.doi.org/10.1097/PAS.0000000000001773DOI Listing
August 2021

Identification of oncological characteristics associated with improved overall survival in patients with adrenocortical carcinoma treated with adjuvant radiation therapy: Insights from the National Cancer Database.

Urol Oncol 2021 Jul 20. Epub 2021 Jul 20.

Department of Surgical Oncology, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA. Electronic address:

Objectives: To test for an association between oncological risk factors and overall survival in patients with non-metastatic adrenocortical carcinoma treated with adjuvant radiation therapy at high-risk for recurrence per NCCN guidelines.

Materials And Methods: We analyzed data from patients undergoing surgical resection with or without aRT in the NCDB from 2004 to 2017. A multivariable Cox proportional hazards model was fit to assess for an association of aRT and OS. To determine whether aRT was associated with improved OS in patients with specific NCCN risk factors, we fit three multivariable Cox proportional hazard models with an interaction term between NCCN risk factors and the use of aRT.

Results: We identified 1,433 patients treated surgically for adrenocortical carcinoma with at least one risk factor. 259 patients received adjuvant radiation therapy (18%) while 1,174 (82%) patients did not. After adjustment, we noted a significant association between adjuvant radiation therapy and overall survival in the entire cohort in the multivariable Cox proportional hazards model (HR 0.68, 95% CI 0.55-0.85, P = 0.001). Adjuvant radiation therapy was associated with increased overall survival in patients with positive surgical margins (HR 0.47, 95% CI 0.35-0.65, P < 0.001), large tumor size ≥6 cm (HR 0.69, 95% CI 0.55-0.87, P = 0.002), and high-grade disease (HR 0.61, 95% CI 0.37-0.99, P = 0.046).

Conclusions: Patients with ACC at high-risk for recurrence were associated with improved overall survival when treated with adjuvant radiation therapy. These data may help identify which patients should consider aRT after resection of clinically localized ACC.
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http://dx.doi.org/10.1016/j.urolonc.2021.06.019DOI Listing
July 2021

Renal mass biopsy: A strategy to reduce associated costs and morbidity when managing localized renal masses.

Urol Oncol 2021 Jul 20. Epub 2021 Jul 20.

Division of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA.

Introduction And Objectives: Renal mass biopsy (RMB) has not been widely adopted in evaluating small renal mass due to concerns for safety, efficacy, and its perceived lack of consequence on management decisions. We assess the potential cost savings and morbidity avoidance of routine RMB on cT1 renal masses undergoing robotic-assisted partial nephrectomy (RAPN).

Methods: We identified n = 920 consecutive RAPN pT1 renal masses and n = 429 consecutive RMBs for cT1 renal masses over 12 years. Using a novel pathological-based risk classification system for cT1 renal masses, we evaluated the morbidity and costs of our RAPN and RMB cohorts. We then define four clinical scenarios where RMB could potentially delay and/or avoid intervention in our pT1 RAPN cohort and model potential complications prevented and cost savings utilizing common clinical scenarios.

Results: Using our risk stratification system in RAPN patients, final histology was classified as benign in n=174 (18.9%) cases, very low-risk (n = 62 [7%]), low-risk (n = 383 [42%]), and high-risk (n = 301 [33%]), respectively. We identified n = 116 (12.6%) Clavien graded peri-operative complications. In our RMB patients, 120 (27.9%), 17 (3.9%), 240 (55.9%), 52(12.1%) were benign, very low, low and high-risk tumors. The median total direct cost for RAPN was $6955/case compared to $1312/case for RMB. If we established a primary goal to avoid immediate extirpative surgery in benign renal tumors, in the elderly (>70 y) with very low-risk tumors and/or those with high renal functional risks (≥ CKD3b), or competing risks (ASA ≥ 3), RMB could have reduced direct costs by approximately 20% and avoided n = 39 Clavien graded complications, seven readmissions, three transfusions, and two returns to the OR. With the additional cost of performing RMB on those not initially biopsied, the net cost saving would be approximately $1.2 million with minimal added complications while still treating high-risk tumors.

Conclusions: Routine RMB before intervention results in cost-saving and complication avoidance. Given the limitations of biopsy, shared decision-making is mandatory. Biopsy should be considered prior to intervention in at-risk populations.
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http://dx.doi.org/10.1016/j.urolonc.2021.06.015DOI Listing
July 2021

Don't SPARE me: details matter!

BJU Int 2021 Oct 13;128(4):525-526. Epub 2021 Jul 13.

Division of Urology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA, USA.

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http://dx.doi.org/10.1111/bju.15405DOI Listing
October 2021

Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline: Part I.

J Urol 2021 Aug 11;206(2):199-208. Epub 2021 Jul 11.

Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Purpose: This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.

Materials/methods: The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).

Results: Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.

Conclusion: Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.
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http://dx.doi.org/10.1097/JU.0000000000001911DOI Listing
August 2021

Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-up: AUA Guideline: Part II.

J Urol 2021 Aug 11;206(2):209-218. Epub 2021 Jul 11.

Consultant Methodologist, Ontario, Canada.

Purpose: This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions.

Materials And Methods: In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).

Results: AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses <2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency.

Conclusion: AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.
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http://dx.doi.org/10.1097/JU.0000000000001912DOI Listing
August 2021

Preventing Prostate Biopsy Complications: to Augment or to Swab?

Urology 2021 Sep 18;155:12-19. Epub 2021 Apr 18.

Department of Urology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA. Electronic address:

Objective: To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy.

Methods: Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed.

Results: 11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P < 0.001). There was no difference in infectious complications between augmented and provider-discretion pathways.

Conclusions: The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.
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http://dx.doi.org/10.1016/j.urology.2021.02.043DOI Listing
September 2021

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

Can J Urol 2021 04;28(2):10620-10624

Fox Chase Cancer Center, Temple University, Philadelphia, Pennsylvania, USA.

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.
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April 2021

Plasma KIM-1 Is Associated with Recurrence Risk after Nephrectomy for Localized Renal Cell Carcinoma: A Trial of the ECOG-ACRIN Research Group (E2805).

Clin Cancer Res 2021 Jun 8;27(12):3397-3403. Epub 2021 Apr 8.

Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Purpose: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy.

Experimental Design: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS).

Results: Plasma from 418 patients was analyzed. Higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42-0.73; < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement ( = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56-0.91; < 0.001).

Conclusions: Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287837PMC
June 2021

Single stage Xi® robotic radical nephroureterectomy for upper tract urothelial carcinoma: surgical technique and outcomes.

Minerva Urol Nephrol 2021 Mar 29. Epub 2021 Mar 29.

Department of Urology, Onze Lieve Vrouw Hospital, Aalst, Belgium.

Background: Radical nephroureterectomy (RNU) represents the standard of care for high grade upper tract urothelial carcinoma (UTUC). Open and laparoscopic approaches are well-established treatments, but evidence regarding robotic RANU is growing. The introduction of the Xi® system facilitates the implementation of this multi-quadrant procedure. The aim of this video-article is to describe the surgical steps and the outcomes of Xi® robotic RNU.

Methods: Single stage Xi® robotic RNU without patients repositioning and robot re-docking were done between 2015 and 2019 and collected in a large worldwide multi-institutional study, the ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST). Institutional review board approval and data share agreement were obtained at each center. Surgical technique is described in detail in the accompanying video. Descriptive statistics of baseline characteristics and surgical, pathological, and oncological outcomes were analyzed. RESULTSː Overall, 148 patients were included in the analysis; 14% had an ECOG >1 and 68.2% ASA ≥3. Median tumor dimension was 3.0 (IQR:2.0-4.2) cm and 34.5% showed hydronephrosis at diagnosis. Forty-eight% were cT1 tumors. Bladder cuff excision and lymph node dissection were performed in 96% and 38.1% of the procedures, respectively. Median operative time and estimated blood loss were 215.5 (IQR:160.5-290.0) minutes and 100.0 (IQR: 50.0-150.0) mL, respectively. Approximately 56% of patients took opioids during hospital stay for a total morphine equivalent dose of 22.9 (IQR:16.0-60.0) milligrams equivalent. Postoperative complications were 26 (17.7%), with 4 major (15.4%). Seven patients underwent adjuvant chemotherapy, with median number of cycles of 4.0 (IQR:3.0-6.0).

Conclusions: Single stage Xi® RNU is a reproducible and safe minimally invasive procedure for treatment of UTUC. Additional potential advantages of the robot might be a wider implementation of LND with a minimally invasive approach.
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http://dx.doi.org/10.23736/S2724-6051.21.04247-8DOI Listing
March 2021

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

BJU Int 2021 Mar 29. Epub 2021 Mar 29.

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

Objectives: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC.

Patients And Methods: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group.

Results: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome.

Conclusion: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.
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http://dx.doi.org/10.1111/bju.15410DOI Listing
March 2021

Predicting Disease Recurrence, Early Progression, and Overall Survival Following Surgical Resection for High-risk Localized and Locally Advanced Renal Cell Carcinoma.

Eur Urol 2021 07 9;80(1):20-31. Epub 2021 Mar 9.

Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

Background: Risk stratification for localized renal cell carcinoma (RCC) relies heavily on retrospective models, limiting their generalizability to contemporary cohorts.

Objective: To introduce a contemporary RCC prognostic model, developed using prospective, highly annotated data from a phase III adjuvant trial.

Design, Setting, And Participants: The model utilizes outcome data from the ECOG-ACRIN 2805 (ASSURE) RCC trial.

Outcome Measurements And Statistical Analysis: The primary outcome for the model is disease-free survival (DFS), with overall survival (OS) and early disease progression (EDP) as secondary outcomes. Model performance was assessed using discrimination and calibration tests.

Results And Limitations: A total of 1735 patients were included in the analysis, with 887 DFS events occurring over a median follow-up of 9.6 yr. Five common tumor variables (histology, size, grade, tumor necrosis, and nodal involvement) were included in each model. Tumor histology was the single most powerful predictor for each model outcome. The C-statistics at 1 yr were 78.4% and 81.9% for DFS and OS, respectively. Degradation of the DFS, DFS validation set, and OS model's discriminatory ability was seen over time, with a global c-index of 68.0% (95% confidence interval or CI [65.5, 70.4]), 68.6% [65.1%, 72.2%], and 69.4% (95% CI [66.9%, 71.9%], respectively. The EDP model had a c-index of 75.1% (95% CI [71.3, 79.0]).

Conclusions: We introduce a contemporary RCC recurrence model built and internally validated using prospective and highly annotated data from a clinical trial. Performance characteristics of the current model exceed available prognostic models with the added benefit of being histology inclusive and TNM agnostic.

Patient Summary: Important decisions, including treatment protocols, clinical trial eligibility, and life planning, rest on our ability to predict cancer outcomes accurately. Here, we introduce a contemporary renal cell carcinoma prognostic model leveraging high-quality data from a clinical trial. The current model predicts three outcome measures commonly utilized in clinical practice and exceeds the predictive ability of available prognostic models.
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http://dx.doi.org/10.1016/j.eururo.2021.02.025DOI Listing
July 2021

A Preoperative Nomogram to Predict Renal Function Insufficiency for Cisplatin-based Adjuvant Chemotherapy Following Minimally Invasive Radical Nephroureterectomy (ROBUUST Collaborative Group).

Eur Urol Focus 2021 Feb 3. Epub 2021 Feb 3.

OLV Hospital, Aalst, Belgium;ORSI Academy, Melle, Belgium.

Background: Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU).

Objective: To create a model predicting renal function decline after minimally invasive RNU.

Design, Setting, And Participants: A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) <50 ml/min/1.73 m at 3 mo after RNU. Patients with baseline eGFR >50 ml/min/1.73 m (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis.

Outcome Measurements And Statistical Analysis: Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR <50 ml/min/1.73 m was built based on the coefficients of the least absolute shrinkage and selection operation (LASSO) logistic regression. The discrimination, calibration, and clinical use of the nomogram were investigated.

Results And Limitations: The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p < 0.001) and cancer-specific death risk (HR: 5.19, p < 0.001) was statistically significant. The limitation mainly lies in its retrospective design.

Conclusions: A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection.

Patient Summary: We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.
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http://dx.doi.org/10.1016/j.euf.2021.01.014DOI Listing
February 2021

Cystoscopy and Systematic Bladder Tissue Sampling in Predicting pT0 Bladder Cancer: A Prospective Trial.

J Urol 2021 06 4;205(6):1605-1611. Epub 2021 Feb 4.

Division of Urological Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Purpose: Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates.

Materials And Methods: Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology.

Results: A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (>pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility.

Conclusions: Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.
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http://dx.doi.org/10.1097/JU.0000000000001602DOI Listing
June 2021

Prescribing Trends in Post-operative Pain Management After Urologic Surgery: A Quality Care Investigation for Healthcare Providers.

Urology 2021 Jul 23;153:156-163. Epub 2021 Jan 23.

Einstein Healthcare Network, Department of Urology, Philadelphia, PA; Fox Chase Cancer Center, Division of Urologic Oncology, Philadelphia, PA. Electronic address:

Objective: To assess prescribing and refilling trends of narcotics in postoperative urology patients at our institution. Although the opioid epidemic remains a public health threat, no series has assessed prescribing patterns across urologic surgery disciplines following discharge.

Methods: All urologic surgeries were retrospectively reviewed from May 2017-April 2018. Demographics, comorbidities, and postoperative pain management strategies were analyzed. Narcotics usage following surgery were reported in total morphine equivalents (TME). Opioid refill rate was characterized by medical specialty and stratified by urologic discipline.

Results: 817 cases were reviewed. Mean age and TME at discharge was 57±15.6 years and 35.43±19.5 mg, respectively. 13.6% (mean age 55±15.9) received a narcotic refill following discharge (mean TME/refill 37.7±28.9 mg). A higher proportion of patients with a pre-operative opioid prescription received a refill compared to opioid naïve patients (38.2% vs 21.6%, P < .01). Refill rate did not differ between urologic subspecialties (P = .3). Urologists were only responsible for 20.4% of all refills filled, despite all patients continuing follow-up with their surgeon. Procedures with the highest rates of post-operative refills were in oncology, male reconstruction/trauma and endourology. Patients with a history of chronic pain (OR 1.9, CI 1.1-3.3) preoperative narcotic prescription (OR 1.6, CI 1.0-2.6), and higher ASA score (OR 1.8, CI 1.6-2.8) were more likely to obtain a postoperative opioid prescription refill.

Conclusion: Approximately 1 in 7 postoperative urology patients receive a postoperative narcotics refill; however, nearly two-thirds receive refills exclusively from non-urologic providers. Attempts to avoid overprescribing of postoperative narcotics need to account for both surgeon and nonsurgeon sources of opioid refills.
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http://dx.doi.org/10.1016/j.urology.2020.11.070DOI Listing
July 2021

Clinical predictors of immediate intervention for isolated renal trauma.

Can J Urol 2020 12;27(6):10456-10460

Department of Urology, Einstein Healthcare Network/Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

INTRODUCTION Evidence suggests overutilization of procedural intervention for renal traumas. The objective of this study was to assess clinical factors associated with procedural intervention for patients presenting to the emergency department (ED) with isolated renal trauma.

Materials And Methods: A United States statewide trauma registry was queried for trauma patients presenting to level I or II trauma centers with isolated renal injuries (Grades I-V) from 2000-2013. Patient demographics, mechanism, American Association for the Surgery of Trauma (AAST) grade, trauma center level designation, presenting ED vital signs, Glasgow Coma Scale (GCS), intubation status, and blood product transfusion were assessed.

Results: Of 449,422 patients, 1383 patients (78% male, median age 29 years [range 2-92]) with isolated renal injuries had data available for analysis. Controlling for demographics, presenting vitals, GCS, trauma center level, mechanism and intubation status, level I status (OR 2.1 [1.3-3.4], p = 0.0021), white race (OR 2.5 [1.3-4.7], p < 0.005), AAST IV/V injury (OR 4.79 [3.1-6.5], p < 0.0001) and blood product administration (OR 2.7 [1.5-4.9], p = 0.0009) were independently associated with an immediate interventional radiology procedure. Independent predictors of immediate surgical intervention include level I status (OR 2.2 [1.2-4.0], p = 0.0075), penetrating mechanism of injury (OR 15.6 [8.4-28.9], p < 0.0001, AAST IV/V injury (OR 13.6 [8.7-21.1], p < 0.0001), and clinical hypotension (SBP < 95 mmHg, OR 2.1 [1.1 4.2], p = 0.03).

Concvlusion: Level 1 trauma center designation, white race, penetrating mechanism of injury, high-grade injury, transfusion of blood products, and hypotension were all independent predictors of immediate procedural intervention following ED presentation with isolated renal trauma.
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December 2020

CRISPR/Cas9 genome-wide loss-of-function screening identifies druggable cellular factors involved in sunitinib resistance in renal cell carcinoma.

Br J Cancer 2020 12 24;123(12):1749-1756. Epub 2020 Sep 24.

Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.

Background: Multi-targeted tyrosine kinase inhibitors (TKIs) are the standard of care for patients with advanced clear cell renal cell carcinoma (ccRCC). However, a significant number of ccRCC patients are primarily refractory to targeted therapeutics, showing neither disease stabilisation nor clinical benefits.

Methods: We used CRISPR/Cas9-based high-throughput loss of function (LOF) screening to identify cellular factors involved in the resistance to sunitinib. Next, we validated druggable molecular factors that are synthetically lethal with sunitinib treatment using cell and animal models of ccRCC.

Results: Our screening identified farnesyltransferase among the top hits contributing to sunitinib resistance in ccRCC. Combined treatment with farnesyltransferase inhibitor lonafarnib potently augmented the anti-tumour efficacy of sunitinib both in vitro and in vivo.

Conclusion: CRISPR/Cas9 LOF screening presents a promising approach to identify and target cellular factors involved in the resistance to anti-cancer therapeutics.
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http://dx.doi.org/10.1038/s41416-020-01087-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723036PMC
December 2020

A Critical Appraisal of the American College of Surgeons Medically Necessary, Time Sensitive Procedures (MeNTS) Scoring System, Urology Consensus Recommendations and Individual Surgeon Case Prioritization for Resumption of Elective Urological Surgery During the COVID-19 Pandemic.

J Urol 2021 01 27;205(1):241-247. Epub 2020 Jul 27.

Department of Urology, Einstein Healthcare Network, Philadelphia, Pennsylvania.

Purpose: Resumption of elective urology cases postponed due to the COVID-19 pandemic requires a systematic approach to case prioritization, which may be based on detailed cross-specialty questionnaires, specialty specific published expert opinion or by individual (operating) surgeon review. We evaluated whether each of these systems effectively stratifies cases and for agreement between approaches in order to inform departmental policy.

Materials And Methods: We evaluated triage of elective cases postponed within our department due to the COVID-19 pandemic (March 9, 2020 to May 22, 2020) using questionnaire based surgical prioritization (American College of Surgeons Medically Necessary, Time Sensitive Procedures [MeNTS] instrument), consensus/expert opinion based surgical prioritization (based on published urological recommendations) and individual surgeon based surgical prioritization scoring (developed and managed within our department). Lower scores represented greater urgency. MeNTS scores were compared across consensus/expert opinion based surgical prioritization and individual surgeon based surgical prioritization scores.

Results: A total of 204 cases were evaluated. Median MeNTS score was 50 (IQR 44, 55), and mean consensus/expert opinion based surgical prioritization and individual surgeon based surgical prioritization scores were 2.6±0.6 and 2.2±0.8, respectively. Median MeNTS scores were 52 (46.5, 57.5), 50 (44.5, 54.5) and 48 (43.5, 54) for individual surgeon based surgical prioritization priority 1, 2 and 3 cases (p=0.129), and 55 (51.5, 57), 47.5 (42, 56) and 49 (44, 54) for consensus/expert opinion based surgical prioritization priority scores 1, 2, and 3 (p=0.002). There was none to slight agreement between consensus/expert opinion based surgical prioritization and individual surgeon based surgical prioritization scores (Kappa 0.131, p=0.002).

Conclusions: Questionnaire based, expert opinion based and individual surgeon based approaches to case prioritization result in significantly different case prioritization. Questionnaire based surgical prioritization did not meaningfully stratify urological cases, and consensus/expert opinion based surgical prioritization and individual surgeon based surgical prioritization frequently disagreed. The strengths and weaknesses of each of these systems should be considered in future disaster planning scenarios.
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http://dx.doi.org/10.1097/JU.0000000000001315DOI Listing
January 2021

Oncologic and Functional Outcomes of Radical and Partial Nephrectomy in pT3a Pathologically Upstaged Renal Cell Carcinoma: A Multi-institutional Analysis.

Clin Genitourin Cancer 2020 12 11;18(6):e723-e729. Epub 2020 May 11.

University of California San Diego, La Jolla, CA. Electronic address:

Background: The efficacy of partial nephrectomy (PN) in setting of pT3a pathologic-upstaged renal cell carcinoma (RCC) is controversial. We compared oncologic and functional outcomes of radical nephrectomy (RN) and PN in patients with upstaged pT3a RCC.

Patients And Methods: This was a multicenter retrospective analysis of patients with cT1-2N0M0 RCC upstaged to pT3a postoperatively. The primary outcome was recurrence-free survival, with secondary outcomes of overall survival and de novo estimated glomular filtration rate (eGFR) < 60. Multivariable analysis was performed to identify predictive factors for oncologic outcomes. Kaplan-Meier analyses (KMA) were obtained to elucidate survival outcomes.

Results: A total of 929 patients had pT3a upstaging (686 [72.6%] RN; 243 [25.7%] PN; mean follow-up, 48 months). Tumor size was similar (RN 7.7 cm vs. PN 7.3 cm; P = .083). PN had decreased ΔeGFR (6.1 vs. RN 19.4 mL/min/1.73m; P < .001) and de novo eGFR < 60 (9.5% vs. 21%; P = .008). Multivariable analysis for recurrence showed increasing RENAL score (hazard ratio [HR], 3.8; P < .001), clinical T stage (HR, 1.8; P < .001), positive margin (HR, 1.57; P = .009), and high grade (HR, 1.21; P = .01) to be independent predictors, whereas surgery was not (P = .076). KMA revealed 5-year recurrence-free survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 79%, 74%, 70%, and 51%, respectively (P < .001). KMA revealed 5-year overall survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 64%, 65.2%, 56.4%, and 55.2%, respectively (P = .059).

Conclusions: In pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit. Surgical decision-making in patients at risk for T3a upstaging should be individualized and driven by tumor as well as functional risks.
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http://dx.doi.org/10.1016/j.clgc.2020.05.002DOI Listing
December 2020

Histone-dependent PARP-1 inhibitors: A novel therapeutic modality for the treatment of prostate and renal cancers.

Urol Oncol 2021 06 8;39(6):312-315. Epub 2020 May 8.

Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA. Electronic address:

Clinical interest in poly(ADP-ribose) polymerase 1 (PARP-1) has increased over the past decade with the recognition of its roles in transcription regulation, DNA repair, epigenetic bookmarking, and chromatin restructuring. A number of PARP-1 inhibitors demonstrating clinical efficacy against tumors of various origins have emerged in recent years. These inhibitors have been essentially designed as nicotinamide adenine dinucleotide (NAD) mimetics. However, because NAD is utilized by many enzymes other than PARP-1, NAD competitors tend to produce certain off-target effects. To overcome the limitation of NAD-like PARP-1 inhibitors, we have developed a new class of PARP-1 inhibitors that specifically targets the histone-dependent route of PARP-1 activation, a mechanism of activation that is unique to PARP-1. Novel histone-dependent inhibitors are highly specific for PARP-1 and demonstrate promising in vitro and in vivo efficacy against prostate and renal tumors. Our findings suggest that novel PARP-1 inhibitors have strong therapeutic potential for the treatment of urological tumors.
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http://dx.doi.org/10.1016/j.urolonc.2020.04.004DOI Listing
June 2021

Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial.

J Urol 2020 Sep 6;204(3):531-537. Epub 2020 Apr 6.

Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Purpose: Everolimus decreases tumor volume of renal angiomyolipomas in patients with tuberous sclerosis. No prospective data are available regarding the effect of everolimus on the growth kinetics in patients with sporadic angiomyolipomas. We sought to determine the safety and efficacy of everolimus in the volumetric reduction of sporadic angiomyolipomas.

Materials And Methods: This multi-institutional, prospective, phase II trial, enrolled patients with 3 cm or larger sporadic angiomyolipomas who were candidates for surgical resection or percutaneous angioembolization. Patients received 10 mg everolimus daily for 4 planned 28-day cycles. Response was defined as a 25% or greater volumetric reduction of patient angiomyolipoma. Baseline, 4, 6 and 12-month volumetric analyses were performed using magnetic resonance imaging. Everolimus was discontinued in those with less than 25% volumetric reduction after 4 cycles. Those with 25% or greater volumetric reduction received 2 additional cycles. The primary outcomes were the efficacy of everolimus in the volumetric reduction of angiomyolipomas by 25% or more, and the safety and tolerability of everolimus.

Results: Overall 20 patients were enrolled at 5 centers. Of these patients 11 (55%) completed 4 cycles and 7 (35%) completed 6 cycles. Efficacy was demonstrated, with 10 of 18 (55.6%) patients exhibiting a 25% or greater reduction in tumor volume at 4 months (median 58.5%) and 10 of 14 (71.4%) patients exhibiting a 25% or greater reduction in tumor volume at 6 months (median 58.2%). Four (20%) patients were withdrawn due to protocol defined toxicities and 8 (40%) self-withdrew from the study due to side effects.

Conclusions: Everolimus was effective in causing volumetric reduction of angiomyolipomas by 25% or greater in most patients but was associated with a high rate of treatment discontinuation.
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http://dx.doi.org/10.1097/JU.0000000000001065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695484PMC
September 2020

Robotic partial nephrectomy vs minimally invasive radical nephrectomy for clinical T2a renal mass: a propensity score-matched comparison from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

BJU Int 2020 07 15;126(1):114-123. Epub 2020 Jun 15.

Department of Urology, UC San Diego School of Medicine, La Jolla, CA, USA.

Objective: To compare outcomes of minimally invasive radical nephrectomy (MIS-RN) and robot-assisted partial nephrectomy (RAPN) in clinical T2a renal mass (cT2aRM).

Patients And Methods: Retrospective, multicentre, propensity score-matched (PSM) comparison of RAPN and MIS-RN for cT2aRM (T2aN0M0). Cohorts were PSM for age, sex, body mass index, American Society of Anesthesiologists (ASA) class, clinical tumour size, and R.E.N.A.L. score using a 2:1 ratio for RN:PN. The primary outcome was disease-free survival (DFS). Secondary outcomes included overall survival (OS), complication rates, and de novo estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m . Multivariable (MVA) and Kaplan-Meier survival analyses (KMSA) were conducted.

Results: In all, 648 patients (216 RAPN/432 MIS-RN) were matched. There were no significant differences in intraoperative complications (P = 0.478), Clavien-Dindo Grade ≥III complications (P = 0.063), and re-admissions (P = 0.238). The MVA revealed high ASA class (hazard ratio [HR] 2.7, P = 0.044) and sarcomatoid (HR 5.3, P = 0.001), but not surgery type (P = 0.601) to be associated with all-cause mortality. Increasing R.E.N.A.L. score (HR 1.31, P = 0.037), high tumour grade (HR 2.5, P = 0.043), and sarcomatoid (HR 2.8, P = 0.02) were associated with recurrence, but not surgery (P = 0.555). Increasing age (HR 1.1, P < 0.001) and RN (HR 3.9, P < 0.001) were predictors of de novo eGFR of <45 mL/min/1.73 m . Comparing RAPN and MIS-RN, KMSA revealed no significant differences for 5-year OS (76.3% vs 88.0%, P = 0.221) and 5-year DFS (78.6% vs 85.3%, P = 0.630) for pT2 RCC, and no differences for 3-year OS (P = 0.351) and 3-year DFS (P = 0.117) for pT3a upstaged RCC. The 5-year freedom from de novo eGFR of <45 mL/min/1.73 m was 91.6% for RAPN vs 68.9% for MIS-RN (P < 0.001).

Conclusions: RAPN had similar oncological outcomes and morbidity profile as MIS-RN, while conferring functional benefit. RAPN may be considered as a first-line option for cT2aRM.
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http://dx.doi.org/10.1111/bju.15064DOI Listing
July 2020

A War on Two Fronts: Cancer Care in the Time of COVID-19.

Ann Intern Med 2020 06 27;172(11):756-758. Epub 2020 Mar 27.

Fox Chase Cancer Center, Philadelphia, Pennsylvania (A.K., D.S.W., M.J.E., E.M.H., R.G.U., R.I.F.).

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http://dx.doi.org/10.7326/M20-1133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133056PMC
June 2020

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

J Clin Oncol 2020 05 2;38(15):1676-1684. Epub 2020 Mar 2.

Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA.

Purpose: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure.

Methods: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment.

Results: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% 7.3%; = .02). There was no difference in ADT use ( = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%).

Conclusion: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.
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http://dx.doi.org/10.1200/JCO.19.01485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238488PMC
May 2020

Overall tumor genomic instability: an important predictor of recurrence-free survival in patients with localized clear cell renal cell carcinoma.

Cancer Biol Ther 2020 05 1;21(5):424-431. Epub 2020 Mar 1.

Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.

Measurement of a tumor's overall genomic instability has gathered recent interest over the identification of specific genomic imbalances, as it may provide a more robust measure of tumor aggressiveness. Here we demonstrate the association of tumor genomic instability in the prediction of disease recurrence in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Genomic copy number analysis was performed using SNP-based microarrays on tumors from 103 ccRCC patients. The number of copy number alterations (CNAs) for each tumor was calculated, and a genomic imbalance threshold (GIT) associated with high stage and high-grade disease was determined. Cox proportional hazards regression analyzes were performed to assess the effect of GIT on recurrence-free survival adjusting for known confounders. In the cohort, copy number losses in chromosome arms 3p, 14q, 6q, 9p, and 1p and gains of 5q and 7p/q were common. CNA burden significantly increased with increasing stage ( < .001) and grade ( < .001). The median CNA burden associated with patients presenting with advanced stage (IV) and high-grade (III/IV) tumors was ≥9, defining the GIT. On regression analysis, GIT was a superior predictor of recurrence (Hazard Ratio 4.44 [CI 1.36-14.48], = .01) independent of stage, with similar results adjusting for grade. These findings were confirmed using an alternative measure of genomic instability, weighted Genomic Integrity Index. Our data support a key role for genomic instability in ccRCC progression. More importantly, we have identified a GIT (≥ 9 CNAs) that is a superior and independent predictor of disease recurrence in high-risk ccRCC patients.
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http://dx.doi.org/10.1080/15384047.2020.1721251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515487PMC
May 2020

Application of Chromosome Microarray Analysis for the Differential Diagnosis of Low-grade Renal Cell Carcinoma With Clear Cell and Papillary Features.

Appl Immunohistochem Mol Morphol 2020 02;28(2):123-129

Department of Pathology.

Clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) are the 2 most common RCCs. However, some RCCs can have both clear cell and papillary features, including clear cell papillary RCC (ccpRCC). They can be a diagnostic challenge in daily practice. Accurate diagnosis of these tumors is important for both patient prognosis and appropriate treatment. Fourteen RCCs with papillary architecture, clear cytoplasm and low Fuhrman grade were analyzed by SNP-based chromosome microarray (CMA). Seven cases had pathologic features of ccpRCC, and all had normal genomic profiles except one that had copy neutral loss of heterozygosity (cnLOH) of chromosome 3 and loss of one copy of the X chromosome. The remaining 7 cases also had papillae and clear cytoplasm. Two of these cases showed losses of chromosome 3 which are typically found in ccRCC. One had a gain of chromosome 7, which is commonly seen in pRCC. The remaining 4 had no alterations of chromosome 3 or 7. However, 3 of these 4 had monosomy 8, which are consistent with RCC with monosomy 8. The remaining case had no copy number alterations. This study shows that low-grade RCC with papillae and clear cell phenotype represents a heterogeneous group, including ccpRCC, ccRCC, pRCC, and RCC with monosomy 8. CMA analysis can be useful for the differential diagnosis of these neoplasms.
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http://dx.doi.org/10.1097/PAI.0000000000000704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434675PMC
February 2020
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