Publications by authors named "Arnav Srivastava"

33 Publications

Editorial Comment.

J Urol 2021 Apr 6:101097JU000000000000169501. Epub 2021 Apr 6.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

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http://dx.doi.org/10.1097/JU.0000000000001695.01DOI Listing
April 2021

A challenging frontier - the genomics and therapeutics of nonclear cell renal cell carcinoma.

Curr Opin Oncol 2021 May;33(3):212-220

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Purpose Of Review: As molecular profiling of renal cell carcinoma (RCC) continues to elucidate novel targets for nonclear cell histologies, understanding the landscape of these targets is of utmost importance. In this review, we highlight the genomic landscape of nonclear cell RCC and its implications for current and future systemic therapies.

Recent Findings: Several genomic studies have described the mutational burden among nonclear cell histologies. These studies have highlighted the importance of MET in papillary RCC and led to several clinical trials evaluating the efficacy of MET inhibitors for papillary RCC. The success of immune checkpoint inhibitors, such as ipilimumab and nivolumab, in clear cell RCC has led to ongoing trials evaluating these novel therapeutics in nonclear cell RCC.

Summary: Genomic profiling has allowed for the evaluation of novel targets for nonclear cell RCC. This evolving therapeutic landscape is being explored in promising, ongoing trials that have the potential for changing how nonclear cell RCC is managed.
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http://dx.doi.org/10.1097/CCO.0000000000000721DOI Listing
May 2021

Management Trends in Pediatric Nonseminomatous Germ Cell Tumors.

Urology 2021 Feb 27. Epub 2021 Feb 27.

Department of Urology, Loyola University Medical Center, Maywood, IL; Department of Urology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.

Objective: To characterize post-orchiectomy treatment trends in prepubescent and adolescent patients with nonseminomatous germ cell tumors (NSGCT) and identify patient and hospital factors associated with receiving surveillance or treatment (chemotherapy or RPLND) after orchiectomy.

Methods: Patients <18 years old diagnosed with NSGCT from 2006 to 2016 were extracted from the National Cancer Database. Patients were stratified into prepubescent (<12 years old) and adolescent (age 13-17) cohorts. National trends and multivariable logistic regression for odds of undergoing treatment were identified.

Results: Documentation of use of post-orchiectomy treatment or surveillance was available for 1006 patients. This population was divided into a prepubescent cohort (≤12 years of age, n = 153) and an adolescent cohort (13-17 years of age, n = 853). 545 (54.4%) patients proceeded with treatment. The proportion of patients undergoing treatment in each cohort remained similar over time, but there was a shift in the adolescent cohort away from RPLND towards chemotherapy. In the prepubescent cohort, pathologic stage group III was associated with undergoing treatment. Older age, >50 miles travel to treatment facility, and higher pathologic stage group were associated with treatment in the adolescent cohort. Black race was associated with decreased odds of undergoing treatment among adolescents.

Conclusion: National treatment trends regarding NSGCT remained similar over a decade. Higher disease stage in prepubescent patients lead to additional post-orchiectomy treatment. Adolescents with NSGCT were more likely to undergo post-orchiectomy treatment if they were older, traveled farther to a treatment center, and had a higher disease stage.
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http://dx.doi.org/10.1016/j.urology.2021.02.024DOI Listing
February 2021

Is fibromyalgia associated with a unique cytokine profile?

Rheumatology (Oxford) 2021 Feb 12. Epub 2021 Feb 12.

Centre for Adolescent Rheumatology Versus Arthritis, University College London, London, U.K.

Objectives: The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokines levels in patients with diffuse CPS (fibromyalgia) versus healthy controls (HC).

Methods: Human studies published in English from the PubMed and MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO(CRD42020193774).

Results: Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared to HC, while the chemokine eotaxin, was consistently raised in fibromyalgia . Meta-analysis showed significantly increased tumour necrosis factor alpha (TNF-α) (SMD=0.36, p = 0.0034, 95%CI=0.12-0.60; I2=71%, Q2 p = 0.0002), interleukin (IL)-6 (SMD=0.15, p = 0.045, %95CI=0.003-0.29; I2=39%, Q2 p = 0.059), IL- 8 (SMD=0.26, p = 0.01, 95%CI =0.05-0.47; I2=61%, Q2 p = 0.005) and IL-10 (SMD=0.61; %95 = 0.34-0.89, p < 0.001; I2 = 10%, Q2 p = 0.34) in fibromyalgia patients compared to HC.

Conclusion: We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared to HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8), and anti-inflammatory cytokines (IL-10) in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.
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http://dx.doi.org/10.1093/rheumatology/keab146DOI Listing
February 2021

Trends in the use of administrative databases in urologic oncology: 2000-2019.

Urol Oncol 2021 Feb 4. Epub 2021 Feb 4.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. Electronic address:

Introduction And Objective: Administrative databases (AD) provide investigators with nationally representative study populations to answer research questions using large sample sizes. We aimed to quantify the trends and incidence of AD use in published manuscripts in urologic oncology. We examined 6 commonly used databases: National Cancer Database, surveillance, epidemiology, and end results database (SEER), SEER-Medicare, Nationwide Inpatient Sample, National Surgical Quality Improvement Program, and Premier Healthcare Database.

Methods: A literature review, powered by PubMed and DistillerSR, aggregated manuscripts that used the aforementioned databases to study a genitourinary malignancy between July 1, 2000 through June 30, 2019. Included publications were categorized by database used, corresponding author department affiliation, organ, journal, year, and contribution - defined as temporal treatment trends, outcomes and survival, comparative effectiveness research, or cost-effectiveness.

Results: There were 2,265 publications across 302 journals that met the inclusion criteria. Between 2000 and 2019 the compound annual growth rate of these publications was 18.7%. SEER use grew at a rate of 14.6% annually. National Cancer Database use grew 28.2% annually. Prostate cancer comprised the majority of publications (51.3%), followed by kidney (23.1%) and bladder (22.5%) cancer. Journals publishing these manuscripts had a median impact factor of 3.28 (IQR = 1.84-5.74) in 2019. Urologists published 52.5% of AD manuscripts over the study period.

Conclusions: Our results show substantial growth in the use of ADs for the study of urologic oncology. Given the broad use of ADs, investigators and specialty societies should advocate for continued improvement in the data captured by them.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.014DOI Listing
February 2021

The Financial Burden of Applying to Urology Residency in 2020.

Urology 2021 Jan 18. Epub 2021 Jan 18.

Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.

Objectives: To determine contemporary costs of preparing for and applying for a urology residency position for the 2019-2020 American Urological Association Match.

Methods: An electronic survey was emailed to all urology residency applicants who applied to Rutgers Robert Wood Johnson Medical School during the 2019-2020 application cycle; it was sent 2 weeks after the Match results were released. We collected information on applicant demographics, interview logistics, and estimated costs incurred applying to residency.

Results: A total of 26% (64/242) of subjects responded, representing all 8 the American Urological Association sections, international schools, and schools without urology programs. 62% were male, 75% were single, and 52% attended public medical school. Applicants paid for the interview trail using loans (67%), family donations (50%), previous or current income (36%), and scholarships (16%). Subjects completed a median of 2 visiting student rotations (IQR 2-3), applied to 80 programs (IQR 66-99), and attended 16 interviews (IQR 13-18.75). The median cost per applicant for the 2019-2020 Match was $9725 (IQR $6134-12,564). This estimate included expenditures on application fees, visiting student rotations, interview trail travel and lodging, research, interview attire, and professional photos. Subjects who attended public medical school were likely to spend $3546.31 (95% confidence interval: 5630.71-1461.916; P < .001) more than those attending private schools.

Conclusion: Urology residency applicants spend almost $10,000 in pursuit of a residency position. These high costs not only contribute to student debt but also may deter applicants from entering the field of urology.
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http://dx.doi.org/10.1016/j.urology.2021.01.013DOI Listing
January 2021

The Feasibility and Efficacy of a Multi-Institutional Urology Boot Camp for Incoming Urology Residents.

Urology 2021 Jan 8. Epub 2021 Jan 8.

Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.

Objectives: To determine the feasibility and perceived usefulness of a pre-residency urology boot camp for first and second year urology residents.

Methods: First and second year urology residents attended a multi-institutional boot camp in July 2019, which consisted of lectures, a hands-on practical, patient simulation session, and networking social event. Attendees completed a pre-course survey where they rated their comfort level in managing interpersonal, post-operative, and urology-specific scenarios on a Likert scale of 0-5. Participants completed follow-up surveys immediately and 6 months after the course regarding confidence in managing the same scenarios and the impact of boot camp on their training.

Results: 6 urology PGY1s (55%) and 5 PGY2s (45%) from 4 institutions attended the boot camp. On the precourse survey, PGY2s had higher average comfort scores compared to PGY1s for all post-operative scenarios besides hypotension but just 2 urology-specific scenarios, difficult Foley troubleshooting (4 vs 3, P < .01) and obstructing urolithiasis with urosepsis (3.6 vs 2.2, P = .05). Immediately after the course, 10 of 11 (91%) residents reported feeling better prepared to handle all scenarios. All participants reported they would recommend this training to other urology residents. Six months later, the majority of respondents reported using knowledge learned in boot camp on a daily basis. All agreed that it was a useful networking experience, and 63% had since contacted other residents they met at the course.

Conclusion: A pre-residency boot camp is both feasible and valuable for first- and second-year urology residents for gaining practical medical knowledge and professional networking.
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http://dx.doi.org/10.1016/j.urology.2020.11.059DOI Listing
January 2021

From Diagnosis to Therapy-PET Imaging for Pheochromocytomas and Paragangliomas.

Curr Urol Rep 2021 Jan 6;22(1). Epub 2021 Jan 6.

Section of Urologic Oncology Surgery, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, 195 Little Albany Street, Room 4563, New Brunswick, NJ, 08903, USA.

Purpose Of Review: Pheochromocytoma and paraganglioma (PPGLs) are neuroendocrine tumors with diverse clinical presentations. PPGLs can be sporadic but often are associated with various syndromes, which can have variable clinical presentations. A thorough workup is therefore critical for staging, treatment, and follow-up. Imaging is an essential part of the workup and diagnosis of PPGLs.

Recent Findings: Improvements in cross-sectional imaging with radionuclides have increased specificity and sensitivity for identifying and treating PPGLs. Furthermore, a variety of targets on PPGLs has allowed for optimal imaging with radionuclides that can be used for staging and treatment. Currently, radionuclides are being evaluated for staging and treatment of PPGLs. Developing novel radionuclides that can identify disease sites and target them simultaneously provides a potential for improving survival and outcomes in patients with PPGLs. Given the clinical diversity among PPGLs, expanding the therapeutic arsenal against locally advanced or metastatic PPGLs can allow clinicians to evaluate and treat PPGLs thoroughly.
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http://dx.doi.org/10.1007/s11934-020-01021-xDOI Listing
January 2021

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

EDITORIAL COMMENT.

Urology 2020 Dec;146:65

Department of Surgery, Division of Urology, Rutgers Robert Wood Johnson University Hospital, New Brunswick, NJ.

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http://dx.doi.org/10.1016/j.urology.2020.08.064DOI Listing
December 2020

Predictors of Recurrence for T3a RCC: A Recurring Conundrum.

Diagnostics (Basel) 2020 Nov 21;10(11). Epub 2020 Nov 21.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ 08902, USA.

Although the gold standard treatment for localized renal cell carcinoma (RCC) is radical nephrectomy (RN) or partial nephrectomy (PN), recurrence rates remain high at 7%, 26%, and 39% for T1, T2, and T3 staged disease, respectively [...].
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http://dx.doi.org/10.3390/diagnostics10110983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700179PMC
November 2020

Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond.

Urol Oncol 2020 Oct 20. Epub 2020 Oct 20.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. Electronic address:

Purpose: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival.

Materials And Methods: We retrospectively abstracted cT1b-T2bN0M0 RCC patients from the National Cancer Database, stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within 1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed overall survival.

Results: A total of 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR = 0.90; 95% CI: 0.77-1.05, P = 0.170), cT2a (OR = 0.90; 95% CI: 0.69-1.19, P = 0.454), or cT2b (OR = 0.96; 95% CI: 0.62-1.51, P = 0.873). In all clinical stage strata, nonclear cell RCCs were significantly less likely to be upstaged (P <0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk.

Conclusion: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574787PMC
October 2020

To Be or "Node" to Be: Nodal Disease and the Role of Lymphadenectomy in the Treatment of Renal Cell Carcinoma.

Med Res Arch 2020 May 25;8(5). Epub 2020 May 25.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

Lymph node involvement in renal cell carcinoma (RCC) correlates with poor oncologic outcomes. However, current RCC staging guidelines may not fully reflect the survival impact of lymph node positive disease. Recent data demonstrates that nodal disease has significant impact on survival and modifications to current staging guidelines have been proposed. Lymph node dissection (LND) at the time of surgical intervention for RCC remains controversial. While clinical trial data have demonstrated conflicting evidence for LND, some institutional studies suggests that carefully selected patients at high-risk for recurrence may benefit from LND. Prospectively, clinical trials are examining treating nodal disease and disease at high-risk of recurrence in the neoadjuvant and/or adjuvant setting at the time of nephrectomy. These promising trials are poised, if successful, to influence the treatment paradigm for localized RCC.
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http://dx.doi.org/10.18103/mra.v8i5.2091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314371PMC
May 2020

The patient-urologist relationship in the COVID-19 era and beyond.

Can Urol Assoc J 2020 Jun;14(6):E271-E273

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States.

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http://dx.doi.org/10.5489/cuaj.6688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654670PMC
June 2020

Impact of pathologic lymph node-positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer.

Cancer 2020 Jul 24;126(13):2991-3001. Epub 2020 Apr 24.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

Background: Stage III renal cell carcinoma (RCC) encompasses both lymph node-positive (pT1-3N1M0) and lymph node-negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer.

Methods: Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node-positive stage III (pT1-3N1M0), lymph node-negative stage III (pT3N0M0), or stage IV metastatic (pT1-3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan-Meier estimates illustrated relative survival when comparing staging groups.

Results: A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node-negative stage III disease, 2218 as having lymph node-positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node-negative stage III disease, but similar survival was noted between patients with lymph node-positive stage III and stage IV RCC, with 5-year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%-63.4%), 22.7% (95% CI, 20.6%-24.9%), and 15.6% (95% CI, 11.1%-23.8%), respectively.

Conclusions: Current RCC staging systems group pT1-3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1-3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.
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http://dx.doi.org/10.1002/cncr.32912DOI Listing
July 2020

Vasovasostomy: kinetics and predictors of patency.

Fertil Steril 2020 04;113(4):774-780.e3

Center for Male Reproductive Medicine and Microsurgery, Cornell Institute for Reproductive Medicine, Department of Urology, Weill Cornell Medicine, New York, New York. Electronic address:

Objective: To assess the timing of patency and late failure (secondary azoospermia) after vasovasostomy (VV) using standardized kinetics definitions.

Design: Retrospective cohort study.

Setting: University-affiliated hospital.

Patient(s): Patients with obstructive azoospermia.

Intervention(s): Vasovasostomy.

Main Outcome Measure(s): Univariate and multivariate logistic regression assessed predictors of patency and late failure. Patency was defined as any sperm return to the ejaculate; and >2 million total motile sperm (TMS) in ejaculate. Late failure after VV was defined as azoospermia; or <2 million TMS in ejaculate.

Result(s): 429 men underwent VV, with median follow up of 242 days. Mean time to patency was 3.25 months versus 5.29 months in the "any sperm" versus ">2 million TMS" groups. Finding sperm intraoperatively during VV significantly improved patency rates in multivariable analysis (odds ratio [OR] 4.22). This association was further boosted when sperm was found bilaterally (OR 6.70). Late failure rate (azoospermia) was 10.6% at mean time of 14.1 months and 23% for <2 million, at mean time of 15.7 months. When assessing predictors of late failure, intraoperative motile sperm bilaterally was a statistically significant protective factor on multivariate analysis (hazard ratio 0.22).

Conclusion(s): Vasovasostomy remains highly efficacious in treating obstructive azoospermia. Young patients, shorter obstructive intervals, and sperm identified intraoperatively predict improved outcomes. Clinicians can expect VV patency in 3 months and late failure within the first 2 years after surgery. However, patency rates, late failure rates, and kinetics vary by definition.
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http://dx.doi.org/10.1016/j.fertnstert.2019.11.032DOI Listing
April 2020

The incidence, predictors, and survival of disappearing small renal masses on active surveillance.

Urol Oncol 2020 02 6;38(2):42.e1-42.e6. Epub 2019 Nov 6.

James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD.

Objective: To evaluate the incidence, predictors, and survival for those small renal masses (SRM, solid mass ≤4 cm suspicious for a clinical T1a renal cell carcinoma) that disappear on imaging while undergoing active surveillance (AS).

Subjects/patients And Methods: The Delayed Intervention and Surveillance for SRM registry prospectively enrolled 739 patients with SRMs. Patients having at least 1 image showing no lesion were considered to have a "disappearing" SRM. Logistic regression assessed predictors of having a disappearing SRM and Kaplan-Meier estimates illustrated relative survival.

Results: Of 374 patients enrolled in AS, 22 (5.9%) experienced a disappearing SRM. Mean time to tumor disappearance was 2.0 years (SD = 1.9) and 50.0% reappeared on subsequent CT imaging. SRM disappearance, most commonly encountered on ultrasound imaging surveillance, was independently associated with tumors <1 cm on multivariable analysis (OR = 10.6 (95% CI: 1.1-100.3), P = 0.04). Furthermore, patients with disappearing SRMs were healthier than other patients on AS with no compromise in overall survival during follow-up (5-year survival = 100% vs. 73.2%, P = 0.06).

Conclusions: Approximately 5% of SRM on AS will disappear during follow-up on surveillance imaging. Most of these represent artifacts of heterogeneous imaging modalities, including ultrasound, and the SRM will reappear on subsequent imaging. Given the indolent nature of these lesions, disappearance events do not require reflex repeat imaging and patients should continue AS with their original surveillance schedule intact. A smaller percentage of patients undergoing AS for a SRM may have a mass the permanently disappears.
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http://dx.doi.org/10.1016/j.urolonc.2019.10.005DOI Listing
February 2020

Clinical Stage Migration and Survival for Renal Cell Carcinoma in the United States.

Eur Urol Oncol 2019 07 25;2(4):343-348. Epub 2018 Sep 25.

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

Background: The rising incidence of renal cell carcinoma (RCC) since the 1980s has been accompanied by stage migration toward early-stage (stage I) cancers. Stage migration drove an apparent increase in survival for RCC since the 1980s, but it is unclear whether it remains a contributor more recently.

Objective: To determine whether clinical stage migration has persisted and the relative impact of stage migration versus improvements in treatment on survival for RCC.

Design, Setting, And Participants: An epidemiologic assessment of stage migration and survival for 262 597 patients at diagnosis of RCC (2004-2015) across >1500 facilities in the National Cancer Database.

Outcome Measurements And Statistical Analysis: Proportion of patients over time was assessed by clinical stage at diagnosis via Cochran-Armitage chi-square tests and linear regression. Mortality data were assessed with the Kaplan-Meier method for 5-yr overall survival, Cox proportional hazards regression, and propensity score matching to differentiate the impact of treatment including systemic therapy from stage migration.

Results And Limitations: Greater diagnosis of clinical stage I disease (70%; p<0.001) was observed, with decreased diagnosis of stage III (8%; p<0.001) and stage IV (11%; p<0.001) up to 2007 followed by stabilization through 2015. Tumor size continues to decrease for localized tumors (mean-0.22cm stage I and-1.24cm stage II, 2004-2015). Histology demonstrated significant associations with stage. Five-year overall survival improved (67.9% [2004] to 72.3% [2010]) with gains in advanced RCC but not localized tumors. Models confirmed improved survival in recent years for stage IV patients. Systemic therapy was associated with improved survival (hazard ratio 0.811 [0.786-0.837], p<0.001). National Cancer Database limitations apply.

Conclusions: The proportion of patients presenting with stage I RCC has stabilized (70%), suggesting that stage migration may have ended. Localized tumors are detected with decreasing size, while advanced cancers have remained stable. Only 11% of patients now present with distant metastatic disease, but 5-yr overall survival is improving in recent years due to improved treatments rather than stage migration.

Patient Summary: In this study, we found that stage migration toward early-stage cancers has ended for renal cell carcinoma (RCC). However, improved treatment for advanced RCC appears to be responsible for improved survival in recent years.
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http://dx.doi.org/10.1016/j.euo.2018.08.023DOI Listing
July 2019

Immune reaction by cytoreductive prostatectomy.

Am J Clin Exp Urol 2019 25;7(2):64-79. Epub 2019 Apr 25.

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, and Division of Urology, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey New Brunswick, NJ, USA.

Prostate cancer (PCa) is the most common non-cutaneous cancer among men and the second leading cause of male cancer deaths in the United States. With no effective cure for advanced disease, the survival rates of castration-resistant disease and metastatic disease remains poor. Treatment via hormonal manipulation, immunotherapy, and chemotherapy remain marginally effective, indicating the need for novel treatment strategies. Cytoreductive prostatectomy (CRP) has grown as a treatment modality for metastatic castration resistant prostate cancer (mCRPC) and an emerging body of literature has demonstrated its survival benefits. In this review, we hope to further explore immunologic changes after CRP and the resultant effects on oncologic outcomes. Conclusively, the data and technical considerations of CRS evolve, CRS may continue to expand treat various type of metastatic cancer. Still, there are little reports about immunological changed after CRP. However, based on technical improvement, CRP and combinational immunotherapy are developing treatments of metastatic disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526355PMC
April 2019

Similar incidence of DNA damage response pathway alterations between clinically localized and metastatic prostate cancer.

BMC Urol 2019 May 6;19(1):33. Epub 2019 May 6.

Section of Urologic Oncology, Division of Urology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 195 Little Albany Street, #4565, New Brunswick, NJ, 08903, USA.

Background: In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study.

Methods: TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis.

Results: DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA > 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291).

Conclusions: Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.
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http://dx.doi.org/10.1186/s12894-019-0453-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501301PMC
May 2019

Strengthening the foundation of kidney cancer treatment and research: revising the AJCC staging system.

Ann Transl Med 2019 Mar;7(Suppl 1):S33

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

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http://dx.doi.org/10.21037/atm.2019.02.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462582PMC
March 2019

The Urology Match Process and the Limited Value of Post-Interview Communication for Program Directors.

Urology 2019 06 4;128:23-30. Epub 2019 Mar 4.

Rutgers Robert Wood Johnson Medical School, Division of Urology, New Brunswick, NJ.

Objective: To understand the urology Match process from the perspective of residency program directors, with a particular focus on the role of postinterview communication. Recent surveys of urology applicants revealed that postinterview communication from programs often violates the rules of the American Urological Association Urology Residency Matching Program (the "Match"), and that such communication may influence applicant rank lists.

Methods: An anonymous, electronic survey seeking information regarding postinterview communication during the Match was sent to all program directors of urology residency programs participating in the 2017 AUA Match cycle.

Results: Of 138 surveys sent, 84 were completed for a 61% response rate. Among respondents, 97.6% percent of programs received postinterview communication from applicants, 76.2% of programs received an informal commitment from an applicant, and 38.3% failed to match an applicant who made an informal commitment. Most program directors (81.7%) responded that promises by applicants did not influence their rank list, and 57.1% state that participating in a second look does not have the potential to influence an applicant's rank order. Cumulatively, 76.2% of program directors felt that it was appropriate for applicants to cancel an interview if they provided 2 or more weeks' notice.

Conclusion: The current study suggests that urology program directors do not ascribe significant value to continued contact with applicants after the interview, regardless of whether such contact is in the form of postinterview communication or in the form of second-look visits.
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http://dx.doi.org/10.1016/j.urology.2019.01.042DOI Listing
June 2019

A Prospective Cohort Study of Postdischarge Opioid Practices After Radical Prostatectomy: The ORIOLES Initiative.

Eur Urol 2019 02 21;75(2):215-218. Epub 2018 Oct 21.

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

Opioid pain medications are overprescribed, but few data are available to help in appropriate tailoring of postdischarge opioid prescriptions after surgery. Prior studies are retrospective and based on incomplete responses (<50%) to questionnaires, with small sample sizes for any particular surgery. The ORIOLES initiative was a prospective cohort study (2017-2018) designed to measure postdischarge opioid prescribing and use and clinical predictors of use for consecutive patients after radical prostatectomy. The objectives were to establish a postdischarge opioid reference value to meet the needs of >80% of patients and compare open and robotic surgery. A total of 205 adult patients were enrolled, with 100% completing follow-up. In units of oral morphine equivalents (OMEQ), a median of 225mg was prescribed and 22.5mg used. There was no difference by surgical approach or among patients with a history of pain-related diagnoses. Overall, 77% of postdischarge opioid medication was unused, with 84% of patients requiring ≤112.5mg OMEQ. Only 9% of patients appropriately disposed of leftover medication. Approximately 5% reported continued incisional pain due to surgery at 30d, but none required continued opioid medication use. Prescribing more opioids was independently associated with greater opioid use in adjusted models. PATIENT SUMMARY: In this report, we looked at opioid medication use following discharge after radical prostatectomy. We found that 77% of opioid pain medication prescribed was unused, with 84% of patients using less than half of their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.
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http://dx.doi.org/10.1016/j.eururo.2018.10.013DOI Listing
February 2019

Spontaneous Regression of a Low-Grade Renal Cell Carcinoma With Oncocytic Features After Renal Mass Biopsy.

Clin Genitourin Cancer 2018 12 21;16(6):e1083-e1085. Epub 2018 Jul 21.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2018.07.012DOI Listing
December 2018

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study.

BJU Int 2019 01 9;123(1):42-50. Epub 2018 Aug 9.

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

Objectives: To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry.

Patients And Methods: Estimated glomerular filtration rate (eGFR) was calculated from creatinine values to determine renal function. QoL was measured using the Short Form 12 (SF-12) questionnaire. The Kaplan-Meier method and Cox proportional hazards regression were used for survival analysis. The mixed-effects model was used for renal function and QoL analysis.

Results: Of 638 patients, 231 (36.2%) chose PN, 41 (6.4%) RN, 27 (4.2%) ablation and 339 (53.1%) AS. Cancer-specific survival at 7 years was 98.8% in PN patients and 100% in all other groups. Overall survival (OS) at 7 years was 87.9%, 90.2%, 83.5% and 66.1% in PN, RN, ablation and AS patients, respectively. The OS rate was significantly worse in the AS group than other groups and likely attributable to older age and increased comorbidities. The eGFR was lowest in RN patients but comparable in all other groups. QoL was lowest in AS patients due to lower physical health scores, but mental health scores were similar in all groups.

Conclusions: With excellent oncological outcomes in all groups, nephron-sparing approaches, like PN and ablation, are preferred over RN when intervention is indicated for SRMs. AS is a reasonable option for select patients, given the comparable oncological and mental health outcomes.
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http://dx.doi.org/10.1111/bju.14490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301094PMC
January 2019

Causes of Artificial Urinary Sphincter Failure and Strategies for Surgical Revision: Implications of Device Component Survival.

Eur Urol Focus 2019 Sep 12;5(5):887-893. Epub 2018 Mar 12.

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Background: Up to 50% of patients receiving an artificial urinary sphincter (AUS) require surgical revision after initial placement. However, the literature is heterogeneous regarding the leading causes of AUS failure and appropriate surgical management.

Objective: To inform a revision approach by tabulating the causes of AUS failure, assessing AUS component survival, and examining the single-component revision efficacy.

Design, Setting, And Participants: We retrospectively reviewed 168 patients receiving AUS placements carried out by a single surgeon from 2008 to 2016 at a high-volume academic institution. The median follow-up from initial placement was 2.7 yr, with 37.5% experiencing recurrent incontinence. The cuff size ranged from 4.0 to 5.5cm, with median size of 4.5cm.

Intervention: Patients without infection or erosion underwent systematic device interrogation and revision, starting with the pressure-regulating balloon (PRB) and then, if necessary, the urethral cuff. Device revision involved either PRB-only correction or cuff and PRB revision.

Outcome Measurements And Statistical Analysis: We used bootstrapped intervals to estimate the mean time to failure for individual AUS components. Kaplan-Meier estimates were used to compare survival for individual components and for revised devices by revision technique.

Results And Limitations: PRB malfunction most commonly caused device failure, while cuff or pump malfunction was rare. Among patients undergoing surgical revision, those with PRB-only correction had similar outcomes to those with more extensive device correction (cuff and PRB exchange; p=0.46). This study, while systematic and detailed, is limited by sample size, follow-up length, and its retrospective nature.

Conclusions: PRB malfunction most commonly caused AUS failure in our cohort. PRB-only correction may satisfactorily restore AUS function in select patients. Consequently, initial interrogation of the PRB may avoid a second incision and urethral exposure for many patients requiring AUS revision.

Patient Summary: Artificial urinary sphincters remain prone to failure over time. In many instances, correcting only the pressure-regulating balloon may effectively restore device function, allowing for a less invasive revision.
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http://dx.doi.org/10.1016/j.euf.2018.02.014DOI Listing
September 2019

Impact of Adjuvant Radiation on Artificial Urinary Sphincter Durability in Postprostatectomy Patients.

Urology 2018 04 5;114:212-217. Epub 2018 Jan 5.

James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD.

Objective: To further understand the implications of adjuvant radiation on artificial urinary sphincter (AUS) durability in postprostatectomy patients.

Methods: One hundred fifty-eight postprostatectomy patients, identified by retrospective chart review, underwent AUS placement by 1 surgeon from 2008 to 2016. Time-to-event analysis measured the effect of adjuvant radiation on all-cause failure, and competing-risks regression stratified failure by cause (infection or erosion, urethral atrophy, mechanical failure).

Results: Adjuvant radiation independently predicted all-cause failure over time (hazard ratio = 4.32, P <.01) When stratifying failure by cause, we find that adjuvant radiation patients have increased risk of infection or erosion complications (hazard ratio = 4.48, P = .03). However, there was no statistical increase in urethral atrophy or mechanical failure. Lastly, among patients who have urethral comorbidities (bladder neck contracture, prior urethral sling, or urethral stricture), those with radiation history have particularly poor outcomes (22.4% revision-free survival at 3 years).

Conclusion: In our series of postprostatectomy patients, adjuvant radiation portends worse AUS device survival over time. Furthermore, this decrease in revision-free survival appears to be concentrated in an increase in infection or erosion complications. Patients with prior urethral injury or manipulation who have also undergone adjuvant radiation should be carefully selected when receiving an AUS as this subset of patients experiences low device survival.
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http://dx.doi.org/10.1016/j.urology.2017.12.029DOI Listing
April 2018

Combining Prostate Health Index density, magnetic resonance imaging and prior negative biopsy status to improve the detection of clinically significant prostate cancer.

BJU Int 2018 04 9;121(4):619-626. Epub 2018 Jan 9.

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

Objectives: To determine the performance of Prostate Health Index (PHI) density (PHID) combined with MRI and prior negative biopsy (PNB) status for the diagnosis of clinically significant prostate cancer (PCa).

Patients And Methods: Patients without a prior diagnosis of PCa, with elevated prostate-specific antigen and a normal digital rectal examination who underwent PHI testing prospectively prior to prostate biopsy were included in this study. PHID was calculated retrospectively using prostate volume derived from transrectal ultrasonography at biopsy. Univariable and multivariable logistic regression modelling, along with receiver-operating characteristic (ROC) curve analysis, was used to determine the ability of serum biomarkers to predict clinically significant PCa (defined as either grade group [GG] ≥2 disease or GG1 PCa detected in >2 cores or >50% of any one core) on biopsy. Age, PNB status and Prostate Imaging Reporting and Data System (PI-RADS) score were incorporated into the regression models.

Results: Of the 241 men who qualified for the study, 91 (37.8%) had clinically significant PCa on biopsy. The median (interquartile range) PHID was 0.74 (0.44-1.24); it was 1.18 (0.77-1.83) and 0.55 (0.38-0.89) in those with and without clinically significant PCa on biopsy, respectively (P < 0.001). On univariable logistic regression, age and PNB status were associated with clinically significant cancer. Of the tested biomarkers, PHID demonstrated the highest discriminative ability for clinically significant disease (area under the ROC curve [AUC] 0.78 for the univariable model). That continued to be the case in multivariable logistic regression models incorporating age and PNB status (AUC 0.82). At a threshold of 0.44, representing the 25th percentile of PHID in the cohort, PHID was 92.3% sensitive and 35.3% specific for clinically significant PCa; the sensitivity and specificity were 93.0% and 32.4% and 97.4% and 29.1% for GG ≥2 and GG ≥3 disease, respectively. In the 104 men who underwent MRI, PI-RADS score was complementary to PHID, with a PI-RADS score ≥3 or, if PI-RADS score ≤2, a PHID ≥0.44, detecting 100% of clinically significant disease. For that subgroup, of the biomarkers tested, PHID (AUC 0.90) demonstrated the highest discriminative ability for clinically significant disease on multivariable logistic regression incorporating age, PNB status and PI-RADS score.

Conclusions: In this contemporary cohort of men undergoing prostate biopsy for the diagnosis of PCa, PHID outperformed PHI and other PSA derivatives in the diagnosis of clinically significant cancer. Incorporating age, PNB status and PI-RADS score led to even further gains in the diagnostic performance of PHID. Furthermore, PI-RADS score was found to be complementary to PHID. Using 0.44 as a threshold for PHID, 35.3% of unnecessary biopsies could have been avoided at the cost of missing 7.7% of clinically significant cancers. Despite these encouraging results, prospective validation is needed.
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http://dx.doi.org/10.1111/bju.14098DOI Listing
April 2018

Retroperitoneal lymph node dissection for testicular seminomas: population-based practice and survival outcomes.

World J Urol 2018 Jan 12;36(1):73-78. Epub 2017 Oct 12.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Marburg 134, Baltimore, MD, 21287, USA.

Purpose: While retroperitoneal lymph node dissection (RPLND) is traditionally reserved for nonseminomatous germ cell tumors, recent efforts to reduce long-term toxicities of radiation and chemotherapy have turned attention to its application for testicular seminomas. Currently, RPLND is reserved for the post-chemotherapy for stage II testicular seminomas; we aimed to describe current utilization of RPNLD for testicular seminomas by stage and implications for survival.

Methods: A national sample of men diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular seminoma (1988-2013) was evaluated from SEER Program registries. Stage-specific utilization of RPLND was determined. Cox proportional hazards models, adjusted for age, race, and radiotherapy, evaluated overall (OS) and cancer-specific survival (CSS) for the RPLND cohort. Adjusted models assessed predictors of RPLND.

Results: A total of 17,681 men (mean age 38.1 years) with testicular seminoma were included with low utilization of RPLND for stage I disease (1.3% overall) and higher rates for stage II disease (10.6% overall). There were no appreciable trends over time. Patients receiving RPLND did not appear to have worse OS or CSS on adjusted stage-by-stage analysis. Higher stage disease (IIA-IIC) was associated with greater need for RPLND while radiotherapy was associated with decreased use [OR 0.40 (0.32-0.51), p < 0.001].

Conclusions: Utilization of RPLND for testicular seminomas in the post-chemotherapy setting has remained stable over a 25-year period. Patients undergoing RPLND are a higher risk cohort but stage-by-stage survival outcomes appeared comparable to men not undergoing RPLND. Upcoming trials implementing RPLND as a first-line modality for testicular seminoma or isolated retroperitoneal relapse will help better quantify relative recurrence and survival.
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http://dx.doi.org/10.1007/s00345-017-2099-0DOI Listing
January 2018

Incidence of T3a up-staging and survival after partial nephrectomy: Size-stratified rates and implications for prognosis.

Urol Oncol 2018 01 29;36(1):12.e7-12.e13. Epub 2017 Sep 29.

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD.

Background: The use of partial nephrectomy (PN) to treat renal cell carcinoma has grown to include larger, more complex tumors. Such tumors are more likely to be up-staged to pT3a and generate controversy regarding the oncologic safety of PN. We aimed to estimate the proportion of patients up-staged to T3a disease after PN, stratified by clinical stage, and characterize their survival.

Methods: From 1998 to 2013, pT1-pT3aN0M0 kidney cancer patients undergoing PN or radical nephrectomy (RN) were identified from the Surveillance Epidemiology and End Results registries. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease to stratified, up-staged pT3a patients undergoing PN. Also, we compared PN patients with up-staged pT3a disease to RN patients with pT3a disease.

Results: From the 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a was 4.2%, 9.5%, and 19.5% for cT1a, cT1b, and cT2, respectively. OS was worse for tumors up-staged from cT1a to pT3a, but not for cT1b or cT2 tumors. Up-staged pT3a tumors across all stage strata demonstrated worse CSS, with worse survival for larger tumors. Analysis revealed no difference in OS or CSS for up-staged pT3a PN patients compared to pT3a RN patients.

Conclusions: A greater proportion of patients experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse CSS across all clinical tumor stages after PN. However, our results do not demonstrate that patients up-staged after PN have compromised oncologic outcomes compared to all-comers with pT3a disease receiving RN.
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http://dx.doi.org/10.1016/j.urolonc.2017.09.005DOI Listing
January 2018