Publications by authors named "Michael A Jewett"

251 Publications

Pathologic concordance of resected metastatic nonseminomatous germ cell tumors in the chest.

J Thorac Cardiovasc Surg 2021 Mar 30;161(3):856-868.e1. Epub 2020 Nov 30.

Division of Thoracic Surgery, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Objective: Men with metastatic nonseminomatous germ cell tumors (NSGCTs) often present with residual chest tumors after chemotherapy. We examined the pathologic concordance of intrathoracic disease and outcomes based on the worst pathology of disease resected at first thoracic surgery.

Methods: A retrospective analysis was performed of consecutive patients undergoing thoracic resection for metastatic NSGCT in our institution between 2005 and 2018.

Results: Eighty-nine patients (all men) were included. The median age was 29 years (interquartile range [IQR], 23-35 years). Primary sites were testis (n = 84; 94.4%) and retroperitoneum (n = 5; 5.6%). Eighty-seven patients received chemotherapy before undergoing surgery. Nineteen patients (21.3%; group 1) had malignancy resected at first surgery (OR1), and the other 70 patients had benign disease at OR1 (78.7%; group 2). Concordant pathology between lungs was 85.2% in group 1 and 91% in group 2, and between lung and mediastinum was 50% in group 1 and 72.7% in group 2. Despite no teratoma at OR1, 3 patients (15.8%) in group 2 had resection of teratoma (n = 2) or malignancy (n = 1) at future surgery. After a mean follow-up of 65.5 months (IQR, 23.1-89.2 months) for group 1 and 47.7 months (IQR, 13.0-75.1 months) for group 2, overall survival was significantly worse for group 1 (68.4% vs 92.9%; P = .03).

Conclusions: The wide range of pathology resected in patients with intrathoracic NSGCT metastases requires careful decision making regarding treatment. Pathologic concordance between lungs is better than that between lung and mediastinum in patients with intrathoracic NSGCT metastases. Aggressive surgical management should be considered for all residual disease due to the low concordance between sites and the potential for excellent long-term survival even in patients with chemotherapy-refractory disease.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.158DOI Listing
March 2021

Hypothermia During Partial Nephrectomy for Patients with Renal Tumors: A Randomized Controlled Trial.

J Urol 2020 Dec 21:101097JU0000000000001517. Epub 2020 Dec 21.

Division of Urology, Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.

Background: Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy.

Methods: We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at six academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of Tc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10ml/min/1.73m at a 5% significance level.

Findings: Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/min/1.73m). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1-year after surgery. The change in mGFR 1-year after surgery was -6.6 ml/min/1.73m in the hypothermia group and -7.8 mL/min/1.73m in the control group (mean difference 1.2 mL/min/1.73m, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 mL/min/1.73m; mean difference 0.5 mL/min/1.73m, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life.

Interpretation: Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.
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http://dx.doi.org/10.1097/JU.0000000000001517DOI Listing
December 2020

Utility of Serum miR-371a-3p in Predicting Relapse on Surveillance in Patients with Clinical Stage I Testicular Germ Cell Cancer.

Eur Urol Oncol 2020 Dec 4. Epub 2020 Dec 4.

Departments of Surgery (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Optimal management of clinical stage I (CSI) testicular cancer is controversial due to lack of robust prognostic factors; miRNA-371a-3p holds promise as a biomarker, although its clinical utility for identifying patients at risk of relapse is unknown.

Objective: To explore the association between serum miR-371a-3p and CSI surveillance relapse.

Design, Setting, And Participants: Serial banked sera from 151 CSI (101 seminomas and 50 nonseminomatous germ cell tumors [NSGCTs]) samples from our Princess Margaret active surveillance cohort were tested.

Outcome Measurements And Statistical Analysis: Using the ampTSmiR test, miR-371a-3p was assayed. Multivariate logistic regression was used to assess the association between postorchiectomy miRNA and relapse.

Results And Limitations: Thirty-four (23%) patients relapsed. There was no association between postorchiectomy miR-371a-3p (2.43 vs 2.74, p =  0.31) or percent decline from before to after orchiectomy (95.8% vs 93.1%, p =  0.14) and relapse. After adjustment for clinical prognostic factors, there remained no association between postorchiectomy miR-371a-3p and relapse (seminoma: odds ratio [OR] 1.33, 95% confidence interval [CI] 0.87-2.02, p =  0.18; NSGCT: OR 0.45, 95% CI 0.21-1.00, p =  0.05). Postorchiectomy miR-371a-3p levels rose as the date of miRNA assessment approached relapse. At relapse, serum markers alpha-fetoprotein and human chorionic gonadotropin were normal in 62%; yet, miR-371a-3p was elevated in 32/34 (94.1%). The magnitude of miR-371a-3p elevation at relapse correlated with disease burden (N1/M0 122.5 vs N2-N3/M0: 521.1; p =  0.05). Limitations include small numbers of relapses and variable time points of serum collection.

Conclusions: In our cohort of CSI testis cancer patients on surveillance, postorchiectomy miR-371a-3p levels were not associated with relapse, suggesting that miR-371a-3p may not be a useful biomarker for guiding adjuvant therapy. Our data suggest that miR-371a-3p holds potential as an early relapse marker and warrants a prospective study, as this may allow a window for less morbid relapse therapy.

Patient Summary: The promising novel blood biomarker for testis cancer miR-371a-3p may not provide information at testicle removal, but serial monitoring may lead to earlier detection of relapse.
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http://dx.doi.org/10.1016/j.euo.2020.11.004DOI Listing
December 2020

Clinical dilemmas in local and regional testis cancer.

Can Urol Assoc J 2021 Jan;15(1):E58-E64

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada.

At the Canadian Testis Cancer Workshop, the multidisciplinary management of testis cancer care was discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents, fellows, nurses, patients, and patient advocacy group members.This review summarizes the discussion regarding clinical dilemmas in local and regional testis cancer. We present cases that highlight the need for a coordinated approach to individualize care. Overarching themes include the importance of a multidisciplinary approach to testis cancer, willingness to involve a high-volume experienced center, and given that the oncological outcomes are excellent, a reminder that clinical decisions need to prioritize selecting a strategy with the least treatment-related morbidity when safe.
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http://dx.doi.org/10.5489/cuaj.6913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769526PMC
January 2021

Long-term Surveillance of Patients with Complete Response Following Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumor.

Eur Urol Oncol 2020 Sep 6. Epub 2020 Sep 6.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

Background: There is controversy regarding the management of patients with normal markers and residual masses (≤1 cm) after chemotherapy for nonseminomatous germ cell tumors (NSGCTs).

Objective: To determine long-term outcomes of a surveillance strategy in such patients.

Design, Setting, And Participants: A retrospective review of our multidisciplinary testicular cancer database was performed. All patients who underwent primary chemotherapy for metastatic NSGCTs were identified between 1981 and 2016. A complete response (CR) was defined as normalization of serum tumor markers and a ≤1 cm residual mass in the largest axial dimension following chemotherapy. All such patients were surveilled.

Outcome Measurements And Statistical Analysis: Outcome variables of interest were time to death, time to cancer-specific survival, and time to relapse. Overall survival and relapse-free survival were calculated using the Kaplan-Meier method, and the cumulative incidence of cause-specific survival rates was calculated using competing risk analysis. The impact of risk group and chemotherapy regimen on relapse-free survival was assessed using log-rank test.

Results And Limitations: During the study period, 1429 metastatic germ cell tumor patients were treated with primary chemotherapy. CR was achieved in 191 (18.5%) NSGCT patients. The median age at diagnosis was 27.4 yr, with a median follow-up of 81.1 mo. The majority had American Joint Committee on Cancer stage II at diagnosis (I: 23.8%; II: 49.2%; III: 27%) and International Germ Cell Cancer Collaborative Group good-risk disease (good: 78%; intermediate: 17.8%; poor: 4.2%). Of the 191 patients with a CR, 175 (91.6%) never relapsed and remain disease free. Sixteen (8.4%) patients relapsed after a median of 11.3 mo (range 1-332 mo), with over half (nine patients; 4.7%) relapsing in the retroperitoneum only and salvaged successfully with postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) alone. Of these nine patients, only two (1%) had viable disease in the PC-RPLND specimen. The remaining seven patients had relapses outside the retroperitoneum and received salvage chemotherapy ± postchemotherapy resection. Overall, nine (4.7%) patients have died, but only four (2.1%) from testis cancer.

Conclusions: Our data, the largest series to date, confirm that surveillance is safe and effective for men who achieve a CR following chemotherapy for metastatic NSGCTs.

Patient Summary: Surveillance is a safe strategy for patients who achieve a complete response following chemotherapy for metastatic testis cancer.
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http://dx.doi.org/10.1016/j.euo.2020.08.007DOI Listing
September 2020

FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment?.

Eur Urol 2020 11 15;78(5):682-687. Epub 2020 Jul 15.

Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands; Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands. Electronic address:

Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis. PATIENT SUMMARY: Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only.
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http://dx.doi.org/10.1016/j.eururo.2020.07.002DOI Listing
November 2020

Small Renal Mass Surveillance: Histology-specific Growth Rates in a Biopsy-characterized Cohort.

Eur Urol 2020 09 14;78(3):460-467. Epub 2020 Jul 14.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre and the University Health Network, University of Toronto, Toronto, ON, Canada.

Background: Most reports of active surveillance (AS) of small renal masses (SRMs) lack biopsy confirmation, and therefore include benign tumors and different subtypes of renal cell carcinoma (RCC).

Objective: We compared the growth rates and progression of different histologic subtypes of RCC SRMs (SRM) in the largest cohort of patients with biopsy-characterized SRMs on AS.

Design, Setting, And Participants: Data from patients in a multicenter Canadian trial and a Princess Margaret cohort were combined to include 136 biopsy-proven SRM lesions managed by AS, with treatment deferred until progression or patient/surgeon decision.

Outcome Measurements And Statistical Analysis: Growth curves were estimated from serial tumor size measures. Tumor progression was defined by sustained size ≥4 cm or volume doubling within 1 yr.

Results And Limitations: Median follow-up for patients who remained on AS was 5.8 yr (interquartile range 3.4-7.5 yr). Clear cell RCC SRMs (SRM) grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/yr on average, respectively, p =  0.0003). Overall, 60 SRM lesions progressed: 49 (82%) by rapid growth (volume doubling), seven (12%) increasing to ≥4 cm, and four (6.7%) by both criteria. Six patients developed metastases, and all were of clear cell RCC histology. Limitations include the use of different imaging modalities and a lack of central imaging review.

Conclusions: Tumor growth varies between histologic subtypes of SRM and among SRM, which likely reflects individual host and tumor biology. Without validated biomarkers that predict this variation, initial follow-up of histologically characterized SRMs can inform personalized treatment for patients on AS.

Patient Summary: Many small kidney cancers are suitable for surveillance and can be monitored over time for change. We demonstrate that different types of kidney cancers grow at different rates and are at different risks of progression. These results may guide better personalized treatment.
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http://dx.doi.org/10.1016/j.eururo.2020.06.053DOI Listing
September 2020

Natural History of Renal Angiomyolipoma Favors Surveillance as an Initial Approach.

Eur Urol Focus 2020 Jul 4. Epub 2020 Jul 4.

Division of Urology, Department of Surgery, Princess Margaret Cancer Center, University of Toronto, ON, Canada. Electronic address:

Background: Traditionally, intervention was recommended for angiomyolipomas (AMLs) >4 cm due to the risk of catastrophic hemorrhage.

Objective: To delineate the natural history of AMLs, including growth rates and need for intervention.

Design, Setting, And Participants: A retrospective review was performed of an AML series from 2002 to 2013, which have been followed prospectively until 2018. We defined lesion size by maximum axial diameter and categorized lesion size at baseline.

Outcome Measurements And Statistical Analysis: A total of 458 patients with 593 AMLs, with a median follow-up of 65.2 mo, were identified. At diagnosis, 534 (90.1%) lesions were ≤4 cm. Forty-three interventions were required for 34 (5.7%) AMLs: 30 were treated with embolization, seven surgery, two with radiofrequency ablation (RFA), three with mammalian target of rapamycin (mTOR) inhibitors, and one with nivolumab when epithelioid AML was confirmed. The median size at intervention was 4.9 cm (range 1.1-29 cm).

Results And Limitations: Most (94%) of the lesions grew slowly (growth rate of <0.25 cm/yr) during the period of observation. The number of AMLs <4 cm needed to treat (NNT) prophylactically to prevent one emergent bleed would have been 136 or that to prevent one blood transfusion would have been 205. The NNT (<4 cm) prophylactically to prevent one elective intervention would have been 82. On multivariate analysis, there were significant differences in intervention rates based on tuberous sclerosis complex, size at presentation, and clinical presentation.

Conclusions: This large single-institution updated series of renal AMLs demonstrates that early intervention is not required, regardless of the traditional 4 cm cut-off. The vast majority of AMLs are indolent lesions that are predominantly asymptomatic and slow growing. Follow-up should be no more frequent than annually.

Patient Summary: The majority of angiomyolipomas (AMLs) are indolent, slow-growing lesions that do not require intervention, regardless of size at presentation. We suggest that surveillance is a safe initial approach for patients presenting with AMLs.
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http://dx.doi.org/10.1016/j.euf.2020.06.004DOI Listing
July 2020

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer (Erratum).

J Biomed Opt 2020 06;25(6)

Princess Margaret Cancer Ctr., Univ. Health Network, Canada.

The erratum corrects a misspelled author surname.
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http://dx.doi.org/10.1117/1.JBO.25.6.069801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317183PMC
June 2020

Shared decision-making for the management of small renal masses: Development and acceptability testing of a novel patient decision aid.

Can Urol Assoc J 2020 Dec;14(12):385-391

Division of Urology, University of Ottawa, Ottawa, ON, Canada.

Introduction: Shared decision-making incorporates patients' values and preferences to achieve high-quality decisions. The objective of this study was to develop an acceptable patient decision aid to facilitate shared decision-making for the management of small renal masses (SRMs).

Methods: The International Patient Decision Aids Standards were used to guide an evidence-based development process. Management options included active surveillance, thermal ablation, partial nephrectomy, and radical nephrectomy. A literature review was performed to provide incidence rates for outcomes of each option. Once a prototype was complete, alpha-testing was performed using a 10-question survey to assess acceptability with patients, patient advocates, urologists, and methodological experts. The primary outcome was acceptability of the decision aid.

Results: A novel patient decision aid was created to facilitate shared decision-making for the management of SRMs. Acceptability testing was performed with 20 patients, 10 urologists, two patient advocates, and one methodological expert. Responders indicated the decision aid was appropriate in length (82%, 27/33), well-balanced (82%, 27/33), and had language that was easy to follow (94%, 31/33). All patient responders felt the decision aid would have been helpful during their consultation and would recommend the decision aid for future patients (100%, 20/20). Most urologists reported they intend to use the decision aid (90%, 9/10).

Conclusions: A novel patient decision aid was created to facilitate shared decision-making for management of SRMs. This clinical tool was acceptable with patients, patient advocates, and urologists and is freely available at: https://decisionaid.ohri.ca/decaids.html.
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http://dx.doi.org/10.5489/cuaj.6575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704079PMC
December 2020

Discrepancy in pathology reports upon second review of radical orchiectomy specimens for testicular germ cell tumors.

Can Urol Assoc J 2020 Dec;14(12):411-415

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada.

Introduction: We sought to evaluate the discrepancies between primary pathology report and second pathology review of radical orchiectomy (RO) specimens.

Methods: A retrospective review was performed of RO specimens from the Ontario Cancer Registry. All cases required both a primary pathology report and a second pathology review from another institution. Histopathological variables assessed included histological subtype and components of mixed germ cell tumor (GCT), pathological tumor (pT) stage, lymphovascular invasion (LVI), spermatic cord invasion, and surgical margin.

Results: Between 1994 and 2015, 5048 ROs were performed with 2719 (53.9%) seminoma and 2029 (40.2%) non-seminoma. Of these, 519 (10.3%) received a second pathology review. There was concordance between primary pathology report and second pathology review in 326 (62.8%) cases. The most common discrepancies involved a change in pT stage (n=148, 28.5%), with upstaging in 83 (16%) and downstaging in 65 (12.5%) cases relative to the original pT stage. The second most common discrepancy regarded the reporting of LVI (n=121, 23.3%), with 62 (11.9%) reporting presence of LVI when the primary pathology report did not. Other discrepancies included a change in the histological subtype in 28 (5.4%) cases and spermatic cord margin status in five (9.6%) cases.

Conclusions: Only 10% of orchiectomy specimens underwent a second pathology review, with nearly 40% of reviews leading to a meaningful change in parameters. Such variation could lead to incorrect tumor staging, estimate of relapse risk, and inappropriate treatment decisions. Expert pathology review of RO specimens should be considered, as it has significant implications for decision-making.
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http://dx.doi.org/10.5489/cuaj.6481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704081PMC
December 2020

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer.

J Biomed Opt 2020 06;25(6):1-13

University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient.

Aim: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall.

Approach: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer's specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram.

Results: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties.

Conclusions: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer's specific uptake ratio.
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http://dx.doi.org/10.1117/1.JBO.25.6.068001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289452PMC
June 2020

A Canadian approach to the regionalization of testis cancer: A review.

Can Urol Assoc J 2020 Oct;14(10):346-351

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine.
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http://dx.doi.org/10.5489/cuaj.6268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716843PMC
October 2020

Psychological distress associated with active surveillance in patients younger than 70 with a small renal mass.

Urol Oncol 2020 06 3;38(6):603.e17-603.e25. Epub 2020 Apr 3.

Urology Division, Surgical Oncology Department, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada.

Purpose: To compare the psychological distress throughout several predefined disease time points in patients younger than 70 with small renal masses (SRMs) treated with either active surveillance (AS) or ablative/surgical therapy.

Methods: Using the Edmonton Symptom Assessment System - revised (ESAS-r) questionnaire, we focused on psychological distress symptoms in all consecutive patients with an SRM between 2014 and 2017. We further evaluated the psychological distress sub-score (PDSS) of ESAS-r, consisting of the sum scores of anxiety, depression, and well-being. PDSS of patients treated with AS or ablation/surgery were compared at 4 distinct time points (before and after diagnosis, after a biopsy is performed, and at last follow-up). Multivariable linear regression models were performed to assess factors associated with worse PDSS (1-point score increase).

Results: We examined 477 patients, of whom 217 and 260 were treated with AS and surgery/ablation, respectively. Similar ESAS-r and PDSS scores were shown at all predefined disease time points except following an SRM biopsy and at last, follow-up, where AS-treated patients with a biopsy-proven malignancy had significantly worse PDSS (11.4 vs. 6.1, P = 0.035), and (13.2 vs. 5.4, P = 0.004), respectively. At last follow-up, multivariable linear models demonstrated that a biopsy-proven malignancy (B = 2.630, 95% CI 0.024-5.236, P = 0.048) and AS strategy (B = 6.499, 95% CI 2.340-10.658, P = 0.002) were associated with worse PDSS in all patients, and in those who underwent a biopsy, respectively.

Conclusions: Offering standardized psychological supportive care may be required for patients younger than 70 years on AS for SRM, especially for those with a biopsy-proven tumor.
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http://dx.doi.org/10.1016/j.urolonc.2020.02.015DOI Listing
June 2020

Required efficacy for novel therapies in BCG-unresponsive non-muscle invasive bladder cancer: Do current recommendations really reflect clinically meaningful outcomes?

Cancer Med 2020 05 12;9(10):3287-3296. Epub 2020 Mar 12.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Background: Single-arm trials are currently an accepted study design to investigate the efficacy of novel therapies (NT) in non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical Bacillus Calmette-Guérin (BCG) immunotherapy as randomized controlled trials are either unfeasible (comparator: early radical cystectomy; ERC), or unethical (comparator: placebo). To guide the design of such single-arm trials, expert groups published recommendations for clinically meaningful outcomes. The aim of this study was to quantitatively verify the appropriateness of these recommendations.

Methods: We used a discrete event simulation framework in combination with a supercomputer to find the required efficacy at which a NT can compete with ERC when it comes to quality-adjusted life expectancy (QALE). In total, 24 different efficacy thresholds (including the recommendations) were investigated.

Results: After ascertaining face validity with content experts, repeated verification, external validation, and calibration we considered our model valid. Both recommendations rarely showed an incremental benefit of the NT over ERC. In the most optimistic scenario, an increase in the IBCG recommendation by 10% and an increase in the FDA/AUA recommendation by 5% would yield results at which a NT could compete with ERC from a QALE perspective.

Conclusions: This simulation study demonstrated that the current recommendations regarding clinically meaningful outcomes for single-arm trials evaluating the efficacy of NT in BCG-unresponsive NMIBC may be too low. Based on our quantitative approach, we propose increasing these thresholds to at least 45%-55% at 6 months and 35% at 18-24 months (complete response rates/recurrence-free survival) to promote the development of clinically truly meaningful NT.
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http://dx.doi.org/10.1002/cam4.2980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221312PMC
May 2020

Predictive Value of In Vivo MR Spectroscopy With Semilocalization by Adiabatic Selective Refocusing in Differentiating Clear Cell Renal Cell Carcinoma From Other Subtypes.

AJR Am J Roentgenol 2020 04 11;214(4):817-824. Epub 2020 Feb 11.

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 610 University Ave, 3-957, Toronto, ON M5G 2M9, Canada.

The purpose of this study is to evaluate the diagnostic value of in vivo MR spectroscopy (MRS) with semilocalization by adiabatic selective refocusing (semi-LASER MRS) in differentiating clear cell renal cell carcinoma (RCC) from the non-clear cell subtype. Sixteen patients with biopsy-proven RCC or masses highly suspicious for RCC were prospectively recruited to participate in the study. Single-voxel H spectra were acquired using a 3-T MRI system, with a semi-LASER sequence acquired for renal tumors in 14 patients and for healthy renal tissue (control tissue) in 12 patients. Offline processing of the MR spectra was performed. MRI and spectra analysis were performed independently by radiologists who were blinded to the reference histopathologic findings. Semi-LASER MRS was diagnostic for nine of 11 patients (82%) with histopathologically proven clear cell RCC, showing a strong lipid peak in seven patients and a weaker lipid resonance in two others, whereas control spectra showed weakly positive findings in only one patient. MRS findings were negative for lipid resonance in two of three patients (67%) with non-clear cell tumors and were weakly positive in another patient. Semi-LASER MRS had a high sensitivity and positive predictive value of 82% and 90%, respectively, in addition to a specificity of 67%, a negative predictive value of 50%, and overall accuracy of 79% for the detection of clear cell RCC. Lipid resonance was detected by MRS for four of six clear cell RCCs with no intravoxel fat on chemical-shift MRI. The preliminary results of the present study show that semi-LASER MRS is promising for the noninvasive discrimination of clear cell RCC from non-clear cell RCC on the basis of detection of lipid resonance and that it provides an incremental yield compared with chemical-shift MRI.
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http://dx.doi.org/10.2214/AJR.19.22023DOI Listing
April 2020

Simultaneous Vs Sequential Retroperitoneal, Thoracic and Cervical Resection of Post Chemotherapy Residual Masses in Patients With Metastatic Nonseminomatous Germ Cell Tumors of the Testis.

Urology 2020 Apr 28;138:69-76. Epub 2020 Jan 28.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

Objective: To compare a simultaneous vs sequential approach to residual post chemotherapy mass resections in metastatic testis cancer.

Methods: A retrospective review was performed of patients who underwent retroperitoneal and thoracic/cervical resection of post chemotherapy residual masses between 2002 and 2018. Group 1: "Simultaneous" (Combined Retroperitoneal and Thoracic/Cervical resections on the same date); Group 2: "Sequential" (Retroperitoneal and Thoracic/Cervical resections at separate dates).

Results: During the study period, 35 simultaneous and 17 sequential resections were performed. The median age at surgery was 28 years (Range 16-61). The median follow-up from last surgical procedure was 62.7 months (Range 0.4-194). Histology revealed teratoma in 38 (73.1%) patients, necrosis in 8 (15.4%) and viable tumor in 6 (11.5%). Discordant pathology findings between thoracic/cervical and abdominal resections were noted in 16 (30.8%) patients. No differences were observed between the simultaneous vs sequential groups in median operating time (585 minutes vs 545 minutes, P = .64), blood loss (1300 vs 1300 mls, P = .42), or length of stay (9 vs 11 days, P = .14). There was no difference between the 5-year (65.7% vs 68.6%) relapse-free survival between the 2 groups (P = .84) or the 5-year (88.6% vs 100%) overall and disease-specific survival (P = .25).

Conclusion: Simultaneous resection of retroperitoneal and thoracic/cervical post chemotherapy metastases is a feasible in some patients. It requires multidisciplinary collaboration and a longer primary procedure.
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http://dx.doi.org/10.1016/j.urology.2019.12.032DOI Listing
April 2020

Identification of tumor size as the only factor associated with nondiagnostic biopsies in patients with small renal masses.

Can Urol Assoc J 2020 May 29;14(5):E220-E223. Epub 2019 Nov 29.

Department of Urology, Memorial University, St. John's, NL, Canada.

Introduction: As greater numbers of small renal masses (SRMs) are discovered incidentally, renal tumor biopsy (RTB) is an increasingly recognized step for the management of these lesions, ideally for the prevention of surgical overtreatment for benign disease. While the diagnosis can often be obtained preoperatively by RTB, indeterminate results create greater difficulty for patients and clinicians. This study examines a series of RTBs, identifying the portion of these that were able to yield a diagnosis, and correlates patient factors, including RENAL and PADUA scoring, with the outcome of a non-diagnostic result.

Methods: Patients were identified as having undergone RTB at the Princess Margaret Cancer Centre in Ontario, Canada, between January 2000 and December 2009. Data was compiled from these 423 patients and analyzed using CART methodology to determine the level of association between various patient and tumor factors and the outcome of a non-diagnostic biopsy. Tumor size was further used to develop a classification tree to describe the prediction of a non-diagnostic biopsy.

Results: Of these 423 patients undergoing RTB, 66 (16%) resulted in a non-diagnostic biopsy. The only patient or tumor factor that was found to be associated with a non-diagnostic outcome was mass size, where small masses (<1.28 cm diameter) were found to have a 38% chance of being non-diagnostic, compared with a 13% chance in those tumors >1.28 cm diameter (86% accuracy, 95% confidence interval [CI] 0.82-0.89).

Conclusions: When evaluating SRMs for diagnostic workup, mass size is the only tumor or patient characteristic associated with a non-diagnostic RTB.
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http://dx.doi.org/10.5489/cuaj.6103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197968PMC
May 2020

Identification of Prognostic Biomarkers in the Urinary Peptidome of the Small Renal Mass.

Am J Pathol 2019 12;189(12):2366-2376

Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Renal cell carcinoma (RCC) is often diagnosed incidentally as a small renal mass (SRM; pT1a, ≤4 cm). Increasing concerns surrounding the overtreatment of patients with benign or clinically silent SRMs has resulted in a recent shift in treatment recommendations, especially in elderly and infirm patients. There are currently no biomarkers that can predict progression. We used a quantitative label-free liquid chromatography-tandem mass spectrometry peptidomics approach and targeted parallel-reaction monitoring to identify early, noninvasive diagnostic and prognostic biomarkers for early-stage RCC-SRMs. In total, 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC-SRM cases, and 26 healthy controls were evaluated. Nine endogenous peptides that displayed significantly elevated expression in clear cell RCC-SRMs relative to healthy controls were identified. Peptides NVINGGSHAGNKLAMQEF, VNVDEVGGEALGRL, and VVAGVANALAHKYH showed significantly elevated expression in clear cell RCC-SRMs relative to renal oncocytoma. Additionally, peptides SHTSDSDVPSGVTEVVVKL and IVDNNILFLGKVNRP displayed significantly elevated expression in progressive relative to nonprogressive clear cell RCC-SRMs. Peptide SHTSDSDVPSGVTEVVVKL showed the most significant discriminatory utility (area under the curve, 0.76; 95% CI, 0.62-0.90; P = 0.0027). Patients with elevated SHTSDSDVPSGVTEVVVKL expression had significantly shorter overall survival (hazard ratio, 4.13; 95% CI, 1.09-15.65; P = 0.024) compared to patients with low expression. Pretreatment characterization of urinary peptides can provide insight into early RCC progression and may aid clinical decision-making and improve disease management.
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http://dx.doi.org/10.1016/j.ajpath.2019.08.015DOI Listing
December 2019

Prognostic urinary miRNAs for the assessment of small renal masses.

Clin Biochem 2020 Jan 28;75:15-22. Epub 2019 Oct 28.

Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Canada; Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. Electronic address:

Background: Renal cell carcinoma (RCC) is often detected incidentally as a small renal mass (SRM; pT1a, ≤4 cm). It is clinically challenging to predict progression in patients with SRMs. This is largely due to the recent recognition of clinically progressive and non-progressive RCC-SRMs. It is critical to accurately stratify SRM patients according to risk to avoid unnecessary treatment. This is especially significant for elderly and infirm patients, where the risk of surgery outweighs mortality from SRMs.

Methods: We employed a qRT-PCR array-based approach and targeted qRT-PCR to identify and validate early, non-invasive diagnostic and prognostic biomarkers of RCC-SRMs. In total, we evaluated eighty urine samples, including 30 renal oncocytoma (≤4 cm) cases, 26 progressive and 24 non-progressive clear cell RCC-SRM (ccRCC-SRM) cases.

Results: We identified nine urinary miRNAs which displayed significantly elevated expression in ccRCC-SRMs (pT1a; ≤4 cm) relative to renal oncocytoma (≤4 cm). Additionally, miR-328-3p displayed significantly down-regulated expression in progressive relative to non-progressive ccRCC-SRMs. Patients with elevated miR-328-3p expression had significantly longer overall survival (HR = 0.29, 95% CI = 0.08-1.03, p = 0.042) compared to patients with low miR-328-3p expression. We also found no significant association between miR-328-3p expression levels and gender, age, laterality, tumor size, or grade, suggesting that miR-328-3p is an independent prognostic biomarker.

Conclusions: Our in-depth miRNA profiling approach identified novel biomarkers for early-stage ccRCC-SRMs. Pretreatment characterization of urinary miRNAs may provide insight into early RCC progression and could potentially aid clinical decision-making, improving patient management and reducing overtreatment.
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http://dx.doi.org/10.1016/j.clinbiochem.2019.10.002DOI Listing
January 2020

Local Recurrence Following Resection of Intermediate-High Risk Nonmetastatic Renal Cell Carcinoma: An Anatomical Classification and Analysis of the ASSURE (ECOG-ACRIN E2805) Adjuvant Trial.

J Urol 2020 04 9;203(4):684-689. Epub 2019 Oct 9.

Fox Chase Cancer Center-Temple Health System, Philadelphia, Pennsylvania.

Purpose: We describe what is to our knowledge a novel classification system for local recurrence after surgery of renal cell carcinoma. We assessed its prognostic implications using prospective, randomized controlled data.

Materials And Methods: We queried the ASSURE (Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery) (ECOG-ACRIN [Eastern Cooperative Oncology Group-American College of Radiology Imaging Network] E2805) trial data for patients with fully resected, intermediate-high risk, nonmetastatic renal cell carcinoma with local recurrence. We used certain definitions, including type I-single recurrence in a remnant kidney or ipsilateral renal fossa, type II-single recurrence in the ipsilateral vasculature, the ipsilateral adrenal gland or a lymph node, type III-single recurrence in other intra-abdominal soft tissues or organs and type IV-any combination of types I-III or multiple recurrences of a single type. Multivariable logistic regression and the log rank test were performed to identify clinicopathological predictors and compare survival, respectively.

Results: Of the 1,943 patients 300 (15.4%) had local recurrence, which was type I, II, III and IV in 66 (22.0%), 97 (32.3%), 87 (29.0%) and 50 (16.7%), respectively. Surgical modality (minimally invasive vs open) and type of surgery (partial vs radical) did not predict any local recurrence. Five-year cancer specific survival and overall survival were worse in patients with type IV recurrence (each p <0.001). There was no difference in survival among patients with types I to III recurrence.

Conclusions: In patients with intermediate-high risk nonmetastatic renal cell carcinoma local recurrence appears to be a function of biology more than of surgical modality or surgery type. The prognosis for solitary intra-abdominal local recurrences appear similar regardless of location (types I-III). Local recurrences involving multiple sites and/or subdivisions are associated with worse survival (type IV).
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http://dx.doi.org/10.1097/JU.0000000000000588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337326PMC
April 2020

Development and acceptability testing of a patient decision aid for individuals with localized renal masses considering surgical removal with partial or radical nephrectomy.

Urol Oncol 2019 11 17;37(11):811.e1-811.e7. Epub 2019 Sep 17.

Division of Urology, University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. Electronic address:

Introduction: Patient decision aids are structured clinical tools that facilitate shared decision-making. In urology, the decision between partial and radical nephrectomy for a renal mass can be difficult. We sought to develop and evaluate a decision aid for patients with a localized renal mass considering surgery. This paper describes the development process and acceptability testing of our patient decision aid.

Material And Methods: A decision aid was systematically created using the International Patient Decision Aids Standards. Review of the literature identified evidence regarding patient-important outcomes of partial and radical nephrectomy. A mixed methods survey was designed to assess acceptability of the decision aid. Kidney cancer survivors, patient advocates, methodological experts, and urologists were recruited to evaluate the decision aid. The primary outcome was the acceptability of the decision aid reported by survey responders.

Results: An evidence-based decision aid was created. Included benefits were overall survival, cancer-free survival, and length of hospital stay. Included harms were postoperative bleeding, urine leak, stage 3 renal failure, renal replacement therapy, and flank bulge. The decision aid met the International Patient Decision Aids Standards defining (6 of 6), certification (6 of 6), and quality criteria (21 of 23). Results of acceptability testing were highly favorable. Responders (n = 22) reported the decision aid had acceptable language (91%), an appropriate length (82%), and presented balanced options (91%). Nine of 11 urologists (82%) reported intended use with future patients.

Conclusions: A novel, evidence-based decision aid was created for patients with renal masses considering surgery. The decision aid is available at https://decisionaid.ohri.ca/AZsumm.php?ID=1913. A separate decision aid addressing the management of small renal masses is currently under development.
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http://dx.doi.org/10.1016/j.urolonc.2019.08.014DOI Listing
November 2019

Searching for prognostic biomarkers for small renal masses in the urinary proteome.

Int J Cancer 2020 04 6;146(8):2315-2325. Epub 2019 Nov 6.

Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early-stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label-free liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC-SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)-SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC-SRMs (ccRCC-SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC-SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC-SRMs. A two-protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70-0.93) in distinguishing progressive from nonprogressive ccRCC-SRMs. Patients (Stage I-IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10 ) compared to patients with no alterations. Our in-depth proteomic analysis identified novel biomarkers for early-stage RCC-SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.
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http://dx.doi.org/10.1002/ijc.32650DOI Listing
April 2020

Re: Adam C. Calaway, Lawrence H. Einhorn, Timothy A. Masterson, Richard S. Foster, Clint Cary. Adverse Surgical Outcomes Associated with Robotic Retroperitoneal Lymph Node Dissection Among Patients with Testicular Cancer. Eur Urol 2019;76:607-9.

Eur Urol 2019 11 17;76(5):e139-e140. Epub 2019 Aug 17.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2019.08.001DOI Listing
November 2019

Comprehensive characterization of a Canadian cohort of von Hippel-Lindau disease patients.

Clin Genet 2019 11 6;96(5):461-467. Epub 2019 Aug 6.

Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.

Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α- or β-domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age-related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web-based design will facilitate broader international collaboration and lead to a better understanding of VHL.
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http://dx.doi.org/10.1111/cge.13613DOI Listing
November 2019

Detection of Relapse by Low-dose Computed Tomography During Surveillance in Stage I Testicular Germ Cell Tumours.

Eur Urol Oncol 2019 07 2;2(4):437-442. Epub 2018 Oct 2.

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; University of Toronto, Toronto, Canada.

Background: Standard-dose computed tomography (SDCT) scans are associated with radiation exposure during stage I testicular cancer surveillance.

Objective: To evaluate low-dose CT (LDCT) for clinical use.

Design, Setting, And Participants: In this single-arm prospective study, patients on surveillance for stage I testicular germ cell tumour underwent SDCT and LDCT scans on their first visit after enrolment. The adequacy of LDCT image quality was assessed for subsequent use. Patients were followed with LDCT only and suspected relapse was confirmed by SDCT.

Outcome Measures And Statistical Analysis: We assessed whether initial LDCT scans were of sufficient quality for routine clinical use. We compared mean differences in nodal size at relapse between LDCT and SDCT using a one-sample paired t test. The relapse free-rate was calculated using the Kaplan-Meier method.

Results And Limitations: Of 257 patients, one was excluded because of inadequate image quality. At median follow-up of 5.25 yr, 35 patients had relapsed, 33 with retroperitoneal lymphadenopathy. The 2- and 5-yr relapse-free rates were 89.5% and 85.3%, respectively. The mean size of retroperitoneal nodal relapse was 17.3 and 17.5mm on the short axis, 23.2 and 22.7mm on the long axis, and 26.1 and 26.7mm on craniocaudal length for LDCT and SDCT, respectively. The mean difference between LDCT and SDCT was 0.14mm (p=0.55) short axis, -0.54mm (p=0.092) long axis, and -0.51mm (p=0.086) length. A limitation was the lack of a control arm.

Conclusions: LDCT image quality was adequate for clinical use, and retroperitoneal nodal relapse was detected with minimal differences seen between LD and SDCT. LDCT can be safely adopted and will decrease overall radiation exposure in stage I germ cell tumour surveillance.

Patient Summary: We studied the use of low-dose computed tomography scans for detecting testicular cancer recurrence in lymph nodes of the abdomen and pelvis and found that they were safe, effective and would potentially reduce overall X-ray exposure. This trial is registered at ClinicalTrials.gov as NCT03142802.
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http://dx.doi.org/10.1016/j.euo.2018.08.031DOI Listing
July 2019

Surgical Safety of Cytoreductive Nephrectomy Following Sunitinib: Results from the Multicentre, Randomised Controlled Trial of Immediate Versus Deferred Nephrectomy (SURTIME).

Eur Urol 2019 10 18;76(4):437-440. Epub 2019 Jun 18.

The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Urology, The Royal Free Hospital and University College London, London, UK. Electronic address:

The European Organisation for Research and Treatment of Cancer SURTIME trial explored timing of sunitinib, a tyrosine kinase inhibitor (TKI), and cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. Previous retrospective studies suggest increased surgery-related adverse events (AEs) after presurgical TKI. We report surgical safety from a randomised comparison of CN before or after sunitinib. In-hospital mortality, 30-d readmission rate, and intraoperative and 30-d postoperative AEs according to Common Terminology Criteria for Adverse Events version 4 and Clavien-Dindo (CD) were analysed. Patients were randomised 1:1 to immediate CN followed by sunitinib versus sunitinib followed by deferred CN 24h after the last dose of sunitinib. None of the tumours in the deferred arm became unresectable, and only two patients had a sunitinib-related delay of CN of >2wk. AEs related to surgery (all grades) in the immediate and deferred arms occurred in 52% and 53% after CN, respectively, although the number of intraoperative surgery-related AEs was higher in the immediate arm. Postoperative AEs (CD ≥3), 30-d readmission, and in-hospital mortality rates were 6.5%, 13%, and 4.3% in the immediate arm and 2.5%, 7.5%, and 2.5% in the deferred arm, respectively. There were no differences in surgery time, blood loss, and hospital stay. PATIENT SUMMARY: Patients with metastatic kidney cancer do not have more surgical complications irrespective of whether they are treated with systemic therapy before or after surgery.
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http://dx.doi.org/10.1016/j.eururo.2019.06.006DOI Listing
October 2019

Predicting Renal Cancer Recurrence: Defining Limitations of Existing Prognostic Models With Prospective Trial-Based Validation.

J Clin Oncol 2019 08 19;37(23):2062-2071. Epub 2019 Jun 19.

1Fox Chase Cancer Center, Philadelphia, PA.

Purpose: To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial.

Patients And Methods: Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities.

Results: Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis.

Conclusion: In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.
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http://dx.doi.org/10.1200/JCO.19.00107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085167PMC
August 2019