Publications by authors named "Nirmish Singla"

161 Publications

The early impact of medicaid expansion on urologic malignancies in the United States.

Urol Oncol 2021 Oct 16. Epub 2021 Oct 16.

Department of Urology, UT Southwestern Medical Center, Dallas, TX. Electronic address:

Purpose: To assess the effects of variable adoption of Medicaid Expansion (ME) of the Affordable Care Act among different states on urologic malignancies using a new variable that defines ME status of patient's residence in a nationwide cancer registry.

Basic Procedures: The National Cancer Database was queried for urologic malignancies (bladder, prostate, kidney and testis) from 2011 to 2016, spanning the period surrounding the primary ME which took place in 2014. Trends in insurance status at time of diagnosis and effects on stage at presentation and survival after ME were evaluated using a difference-in-differences estimator and stratified Cox proportional hazards regression model.

Main Findings: The percentage of patients with Medicaid coverage at the time of diagnosis increased significantly after adoption of ME in ME states across all urologic malignancies. Concurrently, there was a significant decrease in percentage of uninsured patients diagnosed with testis cancer, but not other urologic malignancies, in ME states. A change in the stage at presentation was not observed across all urologic malignancies for patients in ME states after adoption of ME. No difference in overall survival was noted among patients living in a ME state compared to non-ME states with adoption of ME in 2014.

Principal Conclusions: Despite increases in the proportion of patients with Medicaid coverage after 2014 in states that enrolled in ME, there was not an associated change in stage at presentation or survival for patients with genitourinary malignancy.
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http://dx.doi.org/10.1016/j.urolonc.2021.09.002DOI Listing
October 2021

Stereotactic Ablative Radiation Therapy for Oligoprogressive Renal Cell Carcinoma.

Adv Radiat Oncol 2021 Sep-Oct;6(5):100692. Epub 2021 May 26.

Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, Texas.

Purpose: Oligoprogression, defined as limited sites of progression on systemic therapy, in patients with metastatic renal cell carcinoma (mRCC) is not uncommon, possibly because of inter- and intratumoral heterogeneity. We evaluated the effect of stereotactic ablative radiation therapy (SAbR) for longitudinal control of oligoprogressive mRCC.

Methods And Materials: Patients with extracranial mRCC were included in this retrospective analysis if they progressed in ≤3 sites on systemic therapy while demonstrating response/stability at other sites and received SAbR to all progressing sites without switching systemic therapy. Our primary endpoint was modified progression-free survival (mPFS), which we calculated from the start of SAbR to the start of a subsequent systemic therapy, death, or loss to follow-up.

Results: We identified 36 patients with a median follow-up of 20.4 months (interquartile range, 10.9-29.4). Forty-three sites were treated with SAbR with a median dose of 36 Gy (range, 18-50) in 3 fractions (range, 1-5). Median time to SAbR from the start of systemic therapy was 11.4 months (interquartile range, 6.1-17.1). Median mPFS was 9.2 months (95% confidence interval [CI], 5.9-13.2). Patients receiving SAbR while on immunotherapy exhibited a longer median mPFS (>28.4 months, log-rank  = .0001) than patients not on immunotherapy (9.2 months). Median overall survival from SAbR administration was 43.4 months (95% CI, 21.5-not Reached). The 1-year local control rate was 93% (95% CI, 78.7-97.5). Most SAbR-related toxicities were grade 1 to 2 (33% of patients), with one grade 5 hemoptysis event possibly related to SAbR or disease progression.

Conclusions: SAbR has the potential to extend the the duration of current systemic therapy for selected patients with mRCC, preserving subsequent therapies for later administration possibly enabling longer treatment duration.
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http://dx.doi.org/10.1016/j.adro.2021.100692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498727PMC
May 2021

Self-reported quality of life as a predictor of mortality in renal cell carcinoma.

Cancer 2021 Oct 5. Epub 2021 Oct 5.

James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: This study evaluated the utility of self-reported quality of life (QOL) metrics in predicting mortality among all-comers with renal cell carcinoma (RCC) and externally tested the findings in a registry of patients with small renal masses.

Methods: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) captured QOL metrics composed of mental component summary (MCS) and physical component summary (PCS) scores. Regression models assessed associations of MCS and PCS with all-cause, RCC-specific, and non-RCC-specific mortality. Harrell's concordance statistic (the C-index) and the Akaike information criterion (AIC) determined predictive accuracy and parsimony, respectively. Findings were tested in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry.

Results: In SEER-MHOS, 1494 patients had a median age of 73.4 years and a median follow-up time of 5.6 years. Each additional MCS and PCS point reduced the hazard of all-cause mortality by 1.3% (95% CI, 0.981-0.993; P < .001) and 2.3% (95% CI, 0.971-0.984; P < .001), respectively. Models with QOL metrics demonstrated higher predictive accuracy (C-index, 72.3% vs 70.1%) and parsimony (AIC, 9376.5 vs 9454.5) than models without QOL metrics. QOL metrics exerted a greater effect on non-RCC-specific mortality than RCC-specific mortality. External testing in the DISSRM registry confirmed these findings with similar results for all-cause mortality.

Conclusions: Models with self-reported QOL metrics predicted all-cause mortality in patients with RCC with higher accuracy and parsimony than those without QOL metrics. Physical health was a stronger predictor of mortality than mental health. The findings support the incorporation of QOL metrics into prognostic models and patient counseling for RCC.
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http://dx.doi.org/10.1002/cncr.33956DOI Listing
October 2021

Determinants of renal cell carcinoma invasion and metastatic competence.

Nat Commun 2021 10 4;12(1):5760. Epub 2021 Oct 4.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Metastasis is the principal cause of cancer related deaths. Tumor invasion is essential for metastatic spread. However, determinants of invasion are poorly understood. We addressed this knowledge gap by leveraging a unique attribute of kidney cancer. Renal tumors invade into large vessels forming tumor thrombi (TT) that migrate extending sometimes into the heart. Over a decade, we prospectively enrolled 83 ethnically-diverse patients undergoing surgical resection for grossly invasive tumors at UT Southwestern Kidney Cancer Program. In this study, we perform comprehensive histological analyses, integrate multi-region genomic studies, generate in vivo models, and execute functional studies to define tumor invasion and metastatic competence. We find that invasion is not always associated with the most aggressive clone. Driven by immediate early genes, invasion appears to be an opportunistic trait attained by subclones with diverse oncogenomic status in geospatial proximity to vasculature. We show that not all invasive tumors metastasize and identify determinants of metastatic competency. TT associated with metastases are characterized by higher grade, mTOR activation and a particular immune contexture. Moreover, TT grade is a better predictor of metastasis than overall tumor grade, which may have implications for clinical practice.
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http://dx.doi.org/10.1038/s41467-021-25918-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490399PMC
October 2021

Novel Strategies in Locally Advanced Kidney Cancer - Highlights from KEYNOTE-564.

Authors:
Nirmish Singla

Kidney Cancer J 2021 Jun;19(2 Suppl):74

Departments of Urology and Oncology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.52733/kcj19n2-s1-a15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415727PMC
June 2021

Differences between Upper Tract Urothelial Carcinoma and Bladder Cancer.

AUA News 2021 Jul;26(7):15-16

University of Texas Southwestern Medical Center.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415726PMC
July 2021

Decision-making in active surveillance in kidney cancer: current trends and future urine and tissue markers.

World J Urol 2021 Aug 9;39(8):2869-2874. Epub 2021 Aug 9.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Surveillance for small renal masses is a growing choice of management amongst physicians and patients. These decisions, however, can be difficult as patient factors and tumor factors may blur the line between continued surveillance and intervention. Currently, there are no biomarkers that are readily available to aid in the decision making for patients with known renal cell carcinoma; however, many show promise. We herein review the literature of the adjunct tools that are currently available for decision making in small renal masses, but also new potential biomarkers that can potentially be of use.
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http://dx.doi.org/10.1007/s00345-021-03786-3DOI Listing
August 2021

Predictive model for systemic recurrence following cisplatin-based neoadjuvant chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma.

Urol Oncol 2021 Nov 28;39(11):788.e15-788.e21. Epub 2021 Jul 28.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Institute for Urology and Reproductive Health, Sechenov University, Moscow.

Introduction: Neoadjuvant chemotherapy (NAC) is increasingly used prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Systemic recurrence (SR) carries a dismal prognosis. We sought to determine risk factors associated with SR in this setting.

Methods: We evaluated a multi-center database of patients with UTUC who received cisplatin-based NAC before RNU. Final pathology at RNU was dichotomized into ypT<2 vs ypT≥2. Univariable and multivariable analyses were performed to identify risk factors associated with SR. Three groups were defined based on the number of significant risk factors (groups 1, 2, 3 for 0-1, 2, 3 risk factors, respectively) and evaluated for recurrence-free survival (RFS) using the Kaplan-Meier method.

Results: 106 patients were identified between 2004 and 2018. Median age was 67.0 years [IQR = 61-73.3]; 57 (54%) and 49 (46 %) patients received MVAC and GC, respectively. Final pathological stage was ypT<2 in 57 (54%); 23% (24/106) had SR. On univariable analysis, pathological variables on final specimen including ypT≥2, lymphovascular invasion (ypLVI), and nodal involvement were associated with SR. On multivariable analysis, ypLVI OR = 4.1 (95% CI 1.2-13.6; P = 0.024) and pathological nodal involvement OR = 4.5 (95% CI 1.3-15.7; P = 0.017) were predictive of recurrence. Stratifying by the number of risk factors, the 2-year RFS was 95%, 55%, and 18% for groups 1, 2, and 3 respectively (log-rank <0.001).

Conclusion: This model evaluates the risk of SR following NAC and RNU to guide counseling and decision-making after surgery. Adverse pathological variable including ypLVI and nodal involvement, in combination with ypT-stage, are strongly associated with SR.
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http://dx.doi.org/10.1016/j.urolonc.2021.05.037DOI Listing
November 2021

Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma.

Cancer 2021 Nov 19;127(21):3946-3956. Epub 2021 Jul 19.

Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes.

Methods: Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition.

Results: Of 245 treatment-naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P = .003), including none in 71 of 177 patients (40.1%); fewer metastases (P = .011); and higher proportions of clear cell histology (P = .012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13-2.19; P = .007; HR, 2.52; 95% CI, 1.74-3.65; P < .001).

Conclusions: IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications.
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http://dx.doi.org/10.1002/cncr.33790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516697PMC
November 2021

Molecular subtypes of upper tract urothelial cancer: Setting the stage for precision therapy.

Cancer Cell 2021 Jun;39(6):745-747

Upper Tract Urothelial Cancer Program, Johns Hopkins Greenberg Bladder Cancer Institute and Brady Urological Institute, Baltimore, MD.

A comprehensive genomic characterization of a large, high-quality cohort of upper tract urothelial carcinomas (UTUCs) in this issue of Cancer Cell reveals that UTUCs can be divided into five DNA-based molecular subtypes. Feasibility data establish that molecular subtyping can be performed non-invasively by sequencing tumor DNA in urine.
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http://dx.doi.org/10.1016/j.ccell.2021.05.004DOI Listing
June 2021

Locally Advanced Kidney Cancer: A New Space for Immunotherapy?

Eur Urol Oncol 2021 Jun 7. Epub 2021 Jun 7.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.

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http://dx.doi.org/10.1016/j.euo.2021.05.003DOI Listing
June 2021

Volume-outcome relationships for kidney cancer may be driven by disparities and patient risk.

Urol Oncol 2021 07 31;39(7):439.e1-439.e8. Epub 2021 May 31.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: Provider and hospital factors influence healthcare quality, but data are lacking to assess their impact on renal cancer surgery. We aimed to assess factors related to surgeon and hospital volume and study their impact on 30-day outcomes after radical nephrectomy.

Materials And Methods: Renal surgery data were abstracted from Maryland's Health Service Cost Review Commission from 2000 to 2018. Patients ≤18 years old, without a diagnosis of renal cancer, and concurrently receiving another major surgery were excluded. Volume categories were derived from the mean annual cases distribution. Multivariable logistic and linear regression models assessed the association of volume on length of stay, intensive care days, cost, 30-day mortality, readmission, and complications.

Results: 7,950 surgeries, completed by 573 surgeons at 48 hospitals, were included. Demographic, surgical, and admission characteristics differed between groups. Radical nephrectomies performed by low volume surgeons demonstrated increased post-operative complication frequency, mortality frequency, length of stay, and days spent in intensive care relative to other groups. However, after logistic regression adjusting for clinical risk and socioeconomic factors, only increased length of stay and ICU days remained associated with lower surgeon volume. Similarly, after adjusted logistic regression, hospital volume was not associated with the studied outcomes.

Conclusions: Surgeons and hospitals differ in regards to patient demographic and clinical factors. Barriers exist regarding access to high-volume care, and thus some volume-outcome trends may be driven predominantly by disparities and case mix.
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http://dx.doi.org/10.1016/j.urolonc.2021.04.036DOI Listing
July 2021

Serum Small RNA Sequencing and miR-375 Assay Do Not Identify the Presence of Pure Teratoma at Postchemotherapy Retroperitoneal Lymph Node Dissection.

Eur Urol Open Sci 2021 Apr 5;26:83-87. Epub 2021 Mar 5.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Existing tumor markers for testicular germ cell tumor (TGCT) cannot detect the presence of pure teratoma. Serum miRNAs have strong performance detecting other subtypes of TGCT. Previous reports suggest high levels of miR-375 expression in teratoma tissue. The purpose of this study was to explore the role of serum miRNA, including miR-375, in detecting the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We prospectively collected presurgical serum from 40 TGCT patients undergoing PC-RPLND (21 with teratoma at RPLND and 19 with no evidence of disease). We examined the utility of serum miR-375-3p and miR-375-5p by quantitative polymerase chain reaction, and searched for other putative serum miRNAs with small RNA sequencing. The area under the receiver operating characteristic curve (AUC) and univariate analyses were utilized to evaluate test characteristics and predictors of teratoma. Both serum miR-375-3p and miR-375-5p exhibited poor performance (miR-375-3p: 86% sensitivity, 32% specificity, AUC: 0.506; miR-375-5p: 55% sensitivity, 67% specificity, AUC: 0.556). Teratoma at orchiectomy was the only predictor of PC-RPLND teratoma. Small RNA sequencing identified three potentially discriminatory miRNAs, but further validation demonstrated no utility. Our results confirm prior reports that serum miR-375 cannot predict teratoma, and suggest that there may not exist a predictive serum miRNA for teratoma.
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http://dx.doi.org/10.1016/j.euros.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121258PMC
April 2021

Re: Patrick D. McGillivray, Daiki Ueno, Aydin Pooli, et al. Distinguishing Benign Renal Tumors with an Oncocytic Gene Expression (ONEX) Classifier. Eur Urol 2021;79:107-11: Integrating Tc-sestamibi and ONEX to Optimize Risk Stratification for Renal Masses.

Eur Urol 2021 07 2;80(1):e20-e21. Epub 2021 May 2.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.04.020DOI Listing
July 2021

Contemporary Prognostic Model for Renal Cell Carcinoma: Is it Time for Biomarkers?

Eur Urol 2021 07 30;80(1):32-33. Epub 2021 Apr 30.

The Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1016/j.eururo.2021.04.019DOI Listing
July 2021

Local and Regional Recurrences of Clinically Localized Renal Cell Carcinoma after Nephrectomy: A 15 Year Institutional Experience with Prognostic Features and Oncologic Outcomes.

Urology 2021 Aug 20;154:201-207. Epub 2021 Apr 20.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Objective: To evaluate outcomes for patients with local recurrence (LR) of clinically localized renal cell carcinoma (RCC) without concurrent systemic metastasis from our institution, an event that occurs rarely (1%-3%) after surgery. LR may be a harbinger of poor outcomes, and the best management of these patients is unclear.

Materials/methods: We retrospectively reviewed patients surgically treated for clinically localized RCC (cT1-2N0M0) with subsequent LR (in the partial or radical nephrectomy bed) and/or regional recurrence (RR; in the abdomen distant from the direct site of surgery) without concurrent metastasis from our institutional database (2004-2018). Comparative and survival analyses were performed.

Results: Out of 3038 total patients, 1895 had clinically localized RCC, with 30 patients (1.6%) having isolated LR/RR. Median time to recurrence was 26.5 months (IQR:16-35). Of 26 patients treated with local therapy, 14 (53.8%) recurred over a median follow-up time of 29.5 months (IQR:12-45). The 1-year and 2-year secondary recurrence-free survival rates are 60.7% and 49.7%, respectively. Two or more sites of locoregional recurrence significantly predicted secondary recurrence/metastasis after local therapy for local recurrence (hazard ratio: 2.22, P= .04).

Conclusion: Our results suggest local therapy is appropriate for select patients with LR/RR, with almost 50% of patients undergoing a second local therapy remaining alive with "local cure" and no secondary recurrence. The number of sites of recurrence can be used to better select patients that will benefit from local therapy or systemic/combination therapy. This work provides a framework onto which further studies regarding local therapy and locoregional recurrence of RCC can be performed.
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http://dx.doi.org/10.1016/j.urology.2021.03.038DOI Listing
August 2021

Open partial nephrectomy with kidney split: Effective surgical approach to resect completely endophytic tumors.

Urol Oncol 2021 06 12;39(6):371.e1-371.e5. Epub 2021 Apr 12.

Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Objectives: To review perioperative, renal functional, and oncological outcomes of the kidney split technique in performing partial nephrectomy (PN) to resect completely endophytic renal tumors.

Methods: All consecutive patients who underwent open PN with kidney split between 2015 and 2019 at our institution were included. In this approach the kidney is incised along Brodel's line in an avascular plane to locate and then resect the endophytic tumor. Clinicopathologic data, perioperative metrics, complications, renal function, recurrence, and mortality were analyzed using descriptive statistics.

Results: Forty-two open PN with kidney split were performed in 40 patients. No patients required conversion to radical nephrectomy. Most tumors were pT1a renal cell carcinoma (76%), with no recurrences or deaths after a median follow-up of 15 months. All patients had tumors of moderate or high complexity by R.E.N.A.L. nephrometry score. Median cold ischemia time, operative time, estimated blood loss, and inpatient length-of-stay were 34 minutes, 152 minutes, 225 ml, and 2 days, respectively. No patients experienced any Clavien-Dindo grade 4 or 5 complications. Postoperative estimated glomerular filtration rate (eGFR) at last follow-up was >30 ml/min/1.73m in all but one patient, and no patients required dialysis.

Conclusions: The kidney split represents an effective PN technique to resect complex, endophytic renal tumors. In our experience, this technique affords acceptable perioperative outcomes, preserved renal function, and no short-term recurrences or mortality events. Our series highlights the importance of adapting classical surgical techniques, using cold ischemia, and relying on preoperative and intraoperative ultrasonography to effectively guide this complex kidney-sparing operation.
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http://dx.doi.org/10.1016/j.urolonc.2021.02.021DOI Listing
June 2021

Assessing quality of care in the diagnosis and treatment of early-stage testicular cancer: A critical review and summary.

Urol Oncol 2021 07 26;39(7):400-408. Epub 2021 Feb 26.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Objective: To review the current literature on quality of care in the diagnosis and management of early-stage testicular cancer.

Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies on quality of care in testicular cancer diagnosis and management from January 1980 to August 2018. Major overlapping themes related to quality of care in the diagnosis and management of TGCT were identified and evidence related to these themes were abstracted.

Evidence: 62 studies were included in the review. A number of themes were identified including (1) trends in survival and outcomes, (2) management patterns, (3) adherence to evidence-based clinical guidelines, (4) delays in care, (5) treatment complications and toxicities, (6) sociodemographic factors, (7) volume of patients treated, (8) gaps in provider knowledge and medical errors, and (9) multidisciplinary approaches to care.

Evidence Summary: As survival for patients with testicular cancer improves, there has been a greater emphasis on other components of quality of care, such as reducing treatment toxicity and minimizing delays in diagnosis. Efforts to meet these goals include encouragement of adherence to evidence-based guidelines, greater utilization of surveillance, and promotion of multidisciplinary team-based care. Although outcomes have improved, social determinants of health, such as insurance status, race, and geographical residence all may influence survival and cancer-related outcomes. Additionally, qualitative review indicates patients who receive care at high-volume institutions appear to experience better outcomes than those treated at smaller centers.

Conclusions: As outcomes and survival improve for patients with testicular cancer, quality of care has become an important consideration. Future avenues of research on this topic include identifying an appropriate balance between centralization of care and expanding access to underserved areas, minimizing delays in care, ensuring greater adherence to clinical guidelines, and addressing sociodemographic and racial disparities in outcomes.
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http://dx.doi.org/10.1016/j.urolonc.2021.02.001DOI Listing
July 2021

Rational Therapeutic Sequencing in Metastatic Renal Cell Carcinoma: Insights Gained from IMmotion150.

Authors:
Nirmish Singla

Eur Urol 2021 05 16;79(5):674-675. Epub 2021 Feb 16.

Departments of Urology and Oncology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.01.043DOI Listing
May 2021

Neoadjuvant SABR for Renal Cell Carcinoma Inferior Vena Cava Tumor Thrombus-Safety Lead-in Results of a Phase 2 Trial.

Int J Radiat Oncol Biol Phys 2021 07 5;110(4):1135-1142. Epub 2021 Feb 5.

Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Purpose: To evaluate the feasibility, safety, oncologic outcomes, and immune effect of neoadjuvant stereotactic radiation (Neo-SAbR) followed by radical nephrectomy and thrombectomy (RN-IVCT).

Methods And Materials: These are results from the safety lead-in portion of a single-arm phase 1 and 2 trial. Patients with kidney cancer (renal cell carcinoma [RCC]) and inferior vena cava (IVC) tumor thrombus (TT) underwent Neo-SAbR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. Absence of grade 4 to 5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathologic and immunologic alterations attributable to SAbR.

Results: Six patients were included in the final analysis. No grade 4 to 5 AEs were observed. A total of 81 AEs were reported within 90 days of surgery: 73% (59/81) were grade 1, 23% (19/81) were grade 2, and 4% (3/81) were grade 3. After a median follow-up of 24 months, all patients are alive. One patient developed de novo metastatic disease. Of 3 patients with metastasis at diagnosis, 1 had a complete and another had a partial abscopal response without the concurrent use of systemic therapy. Neo-SABR led to decreased Ki-67 and increased PD-L1 expression in the IVC-TT. Inflammatory cytokines and autoantibody titers reflecting better host immune status were observed in patients with nonprogressive disease.

Conclusions: Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment correlated with abscopal response to SABR and RCC relapse-free survival, though direct causal relation to SABR has yet to be established.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.054DOI Listing
July 2021

Academic Mentorship: Choosing the Right Research Mentor(s).

Authors:
Nirmish Singla

Kidney Cancer J 2020 Dec;18(4):114

Departments of Urology and Oncology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808721PMC
December 2020

Clinical utility of the AJCC 8 edition pT1 subclassification and impact on practice patterns in stage I seminoma.

Urol Oncol 2021 02 19;39(2):136.e19-136.e25. Epub 2021 Jan 19.

Department of Urology, University of Texas Southwestern, Dallas, TX. Electronic address:

Background: The American Joint Committee on Cancer 8 edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns have not been studied.

Methods: We retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients.

Results: A total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy -32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated.

Conclusion: The 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.039DOI Listing
February 2021

Harnessing Big Data with Machine Learning in Precision Oncology.

Kidney Cancer J 2020 Sep;18(3):83-84

Division of Hematology/Oncology, Department of Pediatrics, Mount Sinai Hospital, New York, NY.

While multi-level molecular "omic" analyses have undoubtedly increased the sophistication and depth with which we can understand cancer biology, the challenge is to make this overwhelming wealth of data relevant to the clinician and the individual patient. Bridging this gap serves as the cornerstone of precision medicine, yet the expense and difficulty of executing and interpreting these molecular studies make it impractical to routinely implement them in the clinical setting. Herein, we propose that machine learning may hold the key to guiding the future of precision oncology accurately and efficiently. Training deep learning models to interpret the histopathologic or radiographic appearance of tumors and their microenvironment-a phenotypic microcosm of their inherent molecular biology-has the potential to output relevant diagnostic, prognostic, and therapeutic patient-level data. This type of artificial intelligence framework may effectively shape the future of precision oncology by fostering multidisciplinary collaboration.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644120PMC
September 2020

The Significance of Preoperative Serum Sodium and Hemoglobin in Outcomes of Upper Tract Urothelial Carcinoma: Multi-Center Analysis Between China and the United States.

Cancer Manag Res 2020 8;12:9825-9836. Epub 2020 Oct 8.

Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, People's Republic of China.

Purpose: To analyze the effect of preoperative serum sodium and hemoglobin on oncologic outcomes in upper tract urothelial carcinoma (UTUC) based on a multi-center cohort from China and the United States (U.S.).

Methods: We retrospectively reviewed the records of 775 patients with UTUC treated surgically at tertiary care medical facilities in China or the US from 1998 to 2015. We analyzed associations of preoperative serum sodium and hemoglobin with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS) and intravesical recurrence free survival (IVRFS).

Results: The US patients had comparatively lower serum sodium and similar hemoglobin at baseline. Preoperative low serum sodium value was associated with tumor multifocality, lymph node metastasis (LNM) and lymphovascular invasion (LVI); preoperative anemia was associated with advanced age, tumor multifocality, high tumor grade and LVI. Preoperative low serum sodium was an independent predictor of worse OS in the entire cohort; preoperative anemia was an independent predictor of worse OS and CSS in the US cohort alone, Chinese cohort alone and the combined cohort. We developed a predictive nomogram for OS which exhibited better prognostic value when it included the values of sodium and anemia, and successfully validated it in different cohorts.

Conclusion: Preoperative low serum sodium and anemia could be informative in predicting worse pathologic and survival outcomes in different UTUC patient ethnic groups.
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http://dx.doi.org/10.2147/CMAR.S267969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549885PMC
October 2020

Gender Differences in the Clinical Management of clinical T1a Renal Cell Carcinoma.

Urology 2021 May 2;151:129-137. Epub 2020 Sep 2.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: To evaluate gender differences in the management of clinical T1a (cT1a) renal cell carcinoma (RCC) before and after release of the AUA guidelines for management in 2009, which prioritized nephron-sparing approaches.

Methods: Patients aged ≥66 years diagnosed with cT1a RCC from 2004 to 2013 in Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable mixed-effects logistic regression models were used to evaluate factors associated with radical nephrectomy (RN) for cT1a RCC before (2004 to 2009) and after (2010 to 2013) guidelines release. Predictors of pathologic T3 upstaging and high grade pathology in the postguidelines period were examined using multivariable logistic regression among patients who underwent RN or partial nephrectomy.

Results: Twelve thousand four hundred and two patients with cT1a RCC were identified, 42% of whom were women. Overall, the likelihood of RN decreased postguidelines (odds ratio [OR] = 0.44, P <.001), but women were at increased odds of undergoing RN both before and after guideline release (OR = 1.27, P <.001 and OR = 1.37, P <.001, respectively) upon multivariable mixed-effects logistic regression. Tumor size >2 cm was also associated with increased likelihood of RN before and after guidelines (OR = 2.61, P <.001 and OR = 2.51, P <.001, respectively). In the postguidelines period, women had significantly lower odds of pathologic upstaging (OR = 0.75, P = .024) and harboring high grade pathology (OR = 0.71, P <.001) compared to men.

Conclusion: Gender differences persist in the management of cT1a RCC, with women having higher odds of undergoing RN, even after release of AUA guidelines and despite having lower odds of pathologic upstaging and high-grade disease.
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http://dx.doi.org/10.1016/j.urology.2020.08.041DOI Listing
May 2021

Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management.

J Urol 2021 Jan 28;205(1):137-144. Epub 2020 Aug 28.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.

Purpose: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy.

Materials And Methods: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoproteinβ-human chorionic gonadotropinlactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis.

Results: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test.

Conclusions: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.
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http://dx.doi.org/10.1097/JU.0000000000001337DOI Listing
January 2021

Feasibility and Safety of Robotic Excision of Ipsilateral Retroperitoneal Recurrence After Nephrectomy for Renal Cell Carcinoma.

Urology 2020 Nov 21;145:159-165. Epub 2020 Aug 21.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. Electronic address:

Objective: To determine feasibility and safety of robotic excision of local ipsilateral recurrences after nephrectomy for renal cell carcinoma (RCC). Surgical resection is an option for treatment of low burden locally recurrent RCC, potentially delaying the use of systemic therapy. This has historically been performed by open technique, which can impart significant morbidity. We present our experience with robotic excision.

Methods: We reviewed our institutional experience of patients with surgically excised RCC who underwent robotic excision of ipsilateral retroperitoneal recurrence in 2015-2018. Demographics and clinicopathological variables, including operative and postoperative outcomes, were examined.

Results: Twelve robotic excisions of ipsilateral local recurrences were performed in our hospital in 2015-2018. Mean age was 65.48 years (± standard deviation, SD: 9.51), 10 patients were male, and mean BMI 34.75 kg/m (± 6.71). Nine patients recurred after radical nephrectomy, and 3 after partial nephrectomy. Mean size of recurrence was 2.97 cm (±1.69). Mean anesthesia time, EBL, and LOS were 213 minutes (± 38.92), 152 mL (± 130.75), and 43 hours (± 12.64), respectively. All surgical margins were negative. No surgical complications were reported. Median follow-up was 19.0 months [interquartile range, IQR 12.7-30.0]. Five patients out of 12 recurred following robotic excision, these were treated with either systemic therapy, radiation, or palliative surgeries. Mean time for subsequent recurrence was 26.5 months.

Conclusion: In this small case series, robotic excision of ipsilateral RCC retroperitoneal recurrence appears safe, technically feasible, and oncologically sound in expert hands and carefully selected patients.
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http://dx.doi.org/10.1016/j.urology.2020.07.060DOI Listing
November 2020
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