Genetic testing practices among specialist physicians who treat prostate cancer A Canadian, cross-sectional survey.

INTRODUCTION: In patients with prostate cancer (PCa), the identification of an alteration in genes associated with homologous recombination repair (HRR) has implications for prognostication, optimization of therapy, and familial risk mitigation. The aim of this study was to assess the genomic testing landscape of PCa in Canada and to recommend an approach to offering germline and tumor testing for HRR-associated genes. METHODS: The Canadian Genitourinary Research Consortium (GURC) administered a cross-sectional survey to a largely academic, multidisciplinary group of investigators across 22 GURC sites between January and June 2022. RESULTS: Thirty-eight investigators from all 22 sites responded to the survey. Germline genetic testing was initiated by 34%, while 45% required a referral to a genetic specialist. Most investigators (82%) reported that both germline and tumor testing were needed, with 92% currently offering germline and 72% offering tissue testing to patients with advanced PCa. The most cited reasons for not offering testing were an access gap (50%), uncertainties around who to test and which genes to test, (33%) and interpreting results (17%). A majority reported that patients with advanced PCa (74-80%) should be tested, with few investigators testing patients with localized disease except when there is a family history of PCa (45-55%). CONCLUSIONS: Canadian physicians with academic subspecialist backgrounds in genitourinary malignancies recognize the benefits of both germline and somatic testing in PCa; however, there are challenges in accessing testing across practices and specialties. An algorithm to reduce uncertainty for providers when ordering genetic testing for patients with PCa is proposed.

Obesity and Complication Risk From Radical Cystectomy: Identifying a Body Mass Index Threshold.

PURPOSE: There are conflicting reports regarding radical cystectomy complication risk from obesity subcategories, and a BMI threshold below which complication risk is notably reduced is undefined. A BMI threshold may be helpful in prehabilitation to aid patient counseling and inform weight loss strategies to potentially mitigate obesity-associated complication risk. This study aims to identify such a threshold and further investigate the association between BMI subcategories and perioperative complications from radical cystectomy. MATERIALS AND METHODS: Data were extracted from the Canadian Bladder Cancer Information System, a prospective registry across 14 academic centers. Five hundred and eighty-nine patients were analyzed. Perioperative (≤90 days) complications were compared between BMI subcategories. Unconditional multivariable logistic regression and cubic spline analysis were performed to determine the association between BMI and complication risk and identify a BMI threshold. RESULTS: Perioperative complications were reported in 51 (30%), 97 (43%), and 85 (43%) normal, overweight, and obese patients (P = .02). BMI was independently associated with developing any complication (OR 1.04 95% CI 1.01, 1.07). Predicted complication risk began to rise consistently above a BMI threshold of 34 kg/m2. Both overweight (OR 2.00 95% CI 1.26-3.17) and obese (OR 1.98 95% CI 1.24-3.18) patients had increased risk of complications compared to normal BMI patients. CONCLUSIONS: Complication risk from radical cystectomy is independently associated with BMI. Both overweight and obese patients are at increased risk compared to normal BMI patients. A BMI threshold of 34 kg/m2 has been identified, which may inform prehabilitation treatment strategies.

The Comparative Outcomes of Radical Prostatectomy versus Radiotherapy for Nonmetastatic Prostate Cancer: A Longitudinal, Population-Based Analysis.

PURPOSE: The comparative effectiveness of radical prostatectomy (RP) versus radiation therapy (RT) for prostate cancer remains a largely debated topic. Utilizing a provincial population-based linked data set from an equal-access, universal health care system, we sought to compare outcomes among patients treated with either radiation or prostatectomy for nonmetastatic prostate cancer. MATERIALS AND METHODS: We performed a retrospective cohort study by linking several administrative data sets to identify patients who were diagnosed with prostate cancer between 2004 and 2016 in Manitoba, Canada and who were subsequently treated with either RP or RT. Cox proportional hazard models with inverse probability of treatment weighting were used to compare rates of all-cause mortality, as well as prostate cancer specific mortality (PCSM) between patients who underwent RP vs RT. RESULTS: During the study period, 2,540 patients underwent RP and 1,895 underwent RT for prostate cancer. Unadjusted overall survival was higher for RP vs RT (5-year overall survival 95.52% for RP compared with 84.55% for RT, p <0.0001). In inverse probability of treatment weighting-adjusted Cox regression analysis, compared to patients in the RP groups, patients in the RT group had an increased rate of all-cause mortality (HR 1.93, 95% CI 1.65-2.26, p <0.0001), and PCSM (HR 3.98, 95% CI 2.89-5.49; p <0.0001). CONCLUSIONS: RT was associated with higher all-cause mortality and PCSM rates compared with RP. These findings highlight the importance of comparative effectiveness research to identify treatment disparities and warrant further investigation.

Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes From the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort.

OBJECTIVE: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low. METHODS: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis. RESULTS: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48). CONCLUSION: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.

The Association between Income Status and Treatment Selection for Prostate Cancer in a Universal Health Care System: A Population-Based Analysis.

PURPOSE: Treatment selection for localized prostate cancer is guided by risk stratification and patient preferences. While socioeconomic status (SES) disparities exist for access to care, less is known about the effect of SES on treatment decision-making. We sought to evaluate whether income status was associated with the treatment selected (radical prostatectomy [RP] vs radiation therapy [RT]) for nonmetastatic prostate cancer in a universal health care system. MATERIALS AND METHODS: All men from Manitoba, Canada who were diagnosed with nonmetastatic prostate cancer between 2005 and 2016 and subsequently treated with RP or RT were identified using a provincial cancer database. SES was defined as neighborhood income by postal code and divided into income quintiles (Q1-Q5, with Q1 the lowest quintile and Q5 the highest). Multivariable logistic regression nested models were used to compare whether SES was associated with treatment type received. RESULTS: We identified 3,966 individuals who were diagnosed with nonmetastatic prostate cancer and were treated with RP (2,354) or RT (1,612). After adjusting for demographic and clinicopathological characteristics, as income quintile increased, men were incrementally more likely to undergo RP than RT (range Q2 vs Q1: adjusted OR 1.40, 95% CI 1.01-1.93; Q5 vs Q1: adjusted OR 2.30, 95% CI 1.70-3.12). CONCLUSIONS: As income levels increased there was a stepwise incremental increase in the odds of receiving RP over RT for localized prostate cancer. These results may inform initiatives to better understand the values, priorities and barriers that patients experience when making treatment decisions in a universal health care system.

Lymph node dissection during radical nephrectomy: A Canadian multi-institutional analysis.

OBJECTIVES: To determine the association between lymph node dissection (LND) at the time of radical nephrectomy and survival in a large, multi-institutional cohort using a propensity score matching design. SUBJECTS AND METHODS: The Canadian Kidney Cancer information system was used to identify patients undergoing radical nephrectomy for nonmetastatic renal cell carcinoma. Associations between LND with overall survival , recurrence free survival and cancer specific survival were determined using various propensity score techniques in the overall cohort and in patients with varying probabilities of pN1. Cox models were used to determine association of lymph node removed with outcomes. RESULTS: Of the 2,699 eligible patients, 812 (30%) underwent LND. Of the LND patients, 88 (10.8%) had nodal metastases. There was no association between LND and improved overall survival, recurrence free survival or cancer specific survival using various propensity score techniques (stratification by propensity score quintile, matched pairs, inverse treatment probability weighting and adjusted for propensity score quintile). There was no association between LND and a therapeutic benefit in patients with increased threshold probabilities of nodal metastases. Increased number of lymph nodes removed was not associated with improved survival outcomes. CONCLUSIONS: LND at the time of radical nephrectomy for renal cell carcinoma is not associated with improved outcomes. There was no benefit in patients at high risk for nodal metastases, and the number of nodes removed did not correlate with survival. Further studies are needed to determine which high risk patients may benefit from LND.

Determining generalizability of the Canadian Kidney Cancer information system (CKCis) to the entire Canadian kidney cancer population.

INTRODUCTION: The Canadian Kidney Cancer information system (CKCis) has prospectively collected data on patients with renal tumors since January 1, 2011 from 16 sites within 14 academic centers in six provinces. Canadian kidney cancer experts have used CKCis data to address several research questions. The goal of this study was to determine if the CKCis cohort is representative of the entire Canadian kidney cancer population, specifically regarding demographic and geographic distributions. METHODS: The CKCis prospective cohort was analyzed up to December 31, 2018. Baseline demographics and tumor characteristics were analyzed, including location of patients' residence at the time of CKCis entry. Geographic data is presented by province, rural vs. urban via postal code information (2nd digit=0) and by Canadian urban boundary files. To determine the proportion of renal cell carcinoma (RCC) patients that CKCis captures, CKCis accruals were compared to projected Canadian Cancer Society RCC incidence in 2016-2017 and the incidence from the 2016 Canadian Cancer Registry. To determine if the CKCis baseline data is representative, it was compared to registry data and other published data when registry data was not available. RESULTS: This CKCis cohort includes 10 298 eligible patients: 66.6% male, median age 62.6 years; 14.6% had metastatic disease at the time of diagnosis and 70.4% had clear-cell carcinomas. The CKCis cohort captures about 1250 patients per year, which represents approximately 20% of the total kidney cancer incidence. The proportion of patients captured per province did vary from 13-43%. Rural patients make up 17% of patients, with some baseline differences between rural and urban patients. There appears to be no major differences between CKCis patient demographics and disease characteristics compared to national data sources. Canadian heat maps detailing patient location are presented. CONCLUSIONS: CKCis contains prospective data on >10 000 Canadian kidney cancer patients, making it a valuable resource for kidney cancer research. The baseline demographic and geographic data do appear to include a broad cross-section of patients and seem to be highly representative of the Canadian kidney cancer population. Moving forward, future projects will include determining if CKCis cancer outcomes are also representative of the entire Canadian kidney cancer population and studying variations across provinces and within rural vs. urban areas.

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

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 (SRMRCC) 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 SRMRCC 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 (SRMccRCC) grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/yr on average, respectively, p = 0.0003). Overall, 60 SRMRCC 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 SRMRCC and among SRMccRCC, 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.

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC.

INTRODUCTION: Abiraterone acetate plus prednisone (AA+P) has shown to significantly improve survival. COSMiC, a Canadian Observational Study in Metastatic Cancer of the Prostate, set out to prospectively amass real-world data on metastatic castration-resistant prostate cancer (mCRPC) patients managed with AA+P in Canada. Herein, we report their patient-reported outcomes (PROs). METHODS: After a median followup of 67.1 weeks, 254 patients were enrolled across 39 sites. Functional Assessment of Cancer Therapy-Prostate (FACT-P), Montreal Cognitive Assessment (MoCA), Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), and Current Health Satisfaction in Prostate Cancer (CHS-PCa) were evaluated at baseline, as well as at weeks 12, 24, 48, and 72 after AA+P initiation. Descriptive analysis was used with continuous variables. Changes from baseline were summarized using mean (standard deviation [SD]). RESULTS: At a median age of 76.6 (8.94), baseline FACT-P total score was 111.3 (19.56) with no significant change in their functional status observed from baseline over time. The median baseline MoCA score was 25.2 (4.52), yet subsequent assessments showed an absence of cognitive decline while under treatment. Similarly, no meaningful changes were detected in BPI, BFI, and CHS-PCa during the 72-week study period, thus suggesting that patients' PROs were well-maintained throughout AA+P treatment. Prostate-specific antigen (PSA) response with >50% decline was 66.4%. Safety profile was consistent with the known side effect of AA+P. CONCLUSIONS: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real-world, prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study and underscores the importance of PRO use in this complex patient population.

Canadian Update on Surgical Procedures (CUSP) Urology Group consensus for intraoperative hemostasis during minimally invasive partial nephrectomy.

INTRODUCTION: Partial nephrectomy remains the gold standard in the management of small renal masses. However, minimally invasive partial nephrectomy (MIPN) is associated with a steep learning curve, and optimal, standardized techniques for time-efficient hemostasis are poorly described. Given the relative lack of evidence, the goal was to describe a set of actionable guiding principles, through an expert working panel, for urologists to approach hemostasis without compromising warm ischemia or oncological outcomes. METHODS: A three-step modified Delphi method was used to achieve expert agreement on the best practices for hemostasis in MIPN. Panelists were recruited from the Canadian Update on Surgical Procedures (CUSP) Urology Group, which represent all provinces, academic and community practices, and fellowship-and non-fellowship-trained surgeons. Thirty-two (round 1) and 46 (round 2) panellists participated in survey questionnaires, and 22 attended the in-person consensus meeting. RESULTS: An initial literature search of 945 articles (230 abstracts) underwent screening and yielded 24 preliminary techniques. Through sequential survey assessment and in-person discussion, a total of 11 strategies were approved. These are temporally distributed prior to tumor resection (five principles), during tumor resection (two principles), and during renorrhaphy (four principles). CONCLUSIONS: Given the variability in tumor size, depth, location, and vascularity, coupled with limitations of laparoscopic equipment, achieving consistent hemostasis in MIPN may be challenging. Despite over two decades of MIPN experience, limited evidence exists to guide clinicians. Through a three-step Delphi method and rigorous iterative review with a panel of experts, we ascertained a guiding checklist of principles for newly beginning and practicing urologists to reference.

Comparing Perspectives of Canadian Men Diagnosed With Prostate Cancer and Health Care Professionals About Active Surveillance.

Active surveillance (AS) has gained acceptance as a primary management approach for patients diagnosed with low-risk prostate cancer (PC). In this qualitative study, we compared perspectives between patients and health care professionals (HCP) to identify what may contribute to patient-provider discordance, influence patient decision-making, and interfere with the uptake of AS. We performed a systematic comparison of perspectives about AS reported from focus groups with men eligible for AS (7 groups, N = 52) and HCP (5 groups, N = 48) who engaged in conversations about AS with patient. We used conventional content analysis to scrutinize separately focus group transcripts and reached a consensus on similar or divergent viewpoints between them. Patients and clinicians agreed that AS was appropriate for low grade PC and understood the low-risk nature of the disease. They shared the perspective that disease status was a critical factor to pursue or discontinue AS. However, men expressed a greater emphasis on quality of life in their decisions related to AS. Patients and clinicians differed in their perspectives on the clarity, availability, and volume of information needed and offered; clinicians acknowledged variations between HCP when presenting AS, while patients were often compelled to seek additional information beyond what was provided by physicians and experienced difficulty in finding or interpreting information applicable to their situation. A greater understanding of discordant perspectives about AS between patients and HCP can help improve patient engagement and education, inform development of knowledge-based tools or aids for decision-making, and identify areas that require standardization across the clinical practice.

Outcomes and prognosticators of stage 4 renal cell carcinoma with pathological T4 primary lesion using a large, Canadian, multi-institutional database.

INTRODUCTION: The primary objective of this study was to evaluate outcomes and prognosticators in patients who underwent radical nephrectomy (RN) or cytoreductive nephrectomy (CN), depending on the clinical stage of disease preoperatively, with a pathological T4 (pT4) renal cell carcinoma (RCC) outcome. There is little data on the outcome of this specific subset of patients. METHODS: From 2009-2016, we identified patients in the Canadian Kidney Cancer information system (CKCis) who underwent RN or CN and were found to have pT4 RCC. Clinical, operative, and pathological variables were analyzed with univariable and multivariable Cox proportional hazard models to identify factors associated with overall survival (OS). Survival curves were created using Kaplan-Meier methods and compared using the log-rank test. RESULTS: A total of 82 patients were included in the study cohort. Median patient age was 62 years (interquartile range [IQR] 55, 70). Fifty (61%) patients had clear-cell histology and 14 (17%) had sarcomatoid characteristics. Median followup was 12 months (IQR 3, 24). At last followup, eight (10%) patients are alive with no evidence of disease, 27 (33%) are alive with disease, four (5%) were lost to followup, 36 (44%) died of disease, and seven (8%) died of other causes. Tumor histological subtype (clear-cell vs. non-clear-cell) (p=0.0032), larger tumor size (cm) (p=0.012), and Fuhrman grade (G4 vs. G2-G3) (p=0.045) were significantly associated with mortality in a multivariable Cox regression model. CONCLUSIONS: For patients with pT4 RCC after RN or CN, survival is poor. Sarcomatoid features, non-clear-cell histology, and presence of systemic symptoms were associated with worse OS.

Development and Acceptability Testing of a Patient Decision Aid for Urinary Diversion with Radical Cystectomy.

PURPOSE: The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion. MATERIALS AND METHODS: We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid. RESULTS: Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria. CONCLUSIONS: We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.

Long-Term Surveillance of Complex Cystic Renal Masses and Heterogeneity of Bosniak 3 Lesions.

PURPOSE: We sought to better characterize the frequency of Bosniak cyst class changes, identify predictors of change and progression, determine the average growth rate of cysts and validate the safety of active surveillance. MATERIALS AND METHODS: Consecutive patients referred for the management of complex cysts (Bosniak 2F or greater) were included in analysis. All imaging studies were reevaluated and any stage change was reviewed with a blinded genitourinary radiologist. Bosniak 3 cysts were subclassified as 3s-septated enhancing Bosniak cysts and 3n-cysts with wall or septation-only nodularity. A multivariate Cox proportional hazards model was used to identify predictors of the Bosniak classification change. Kaplan-Meier curves were applied to analyze Bosniak cyst progression and regression. RESULTS: A total 140 lesions were included in study, necessitating review of a total of 1,011 abdominal scans in 111 patients. Median followup was 46 months (IQR 23-65.5) and patients underwent a mean of 6.8 diagnostic scans. On multivariate analysis nodular cysts progressed (HR 6.16, 95% CI 2.58-14.72, p <0.00004) and entirely endophytic cysts were less likely to progress (HR 0.21, 95% CI 0.05-0.85, p = 0.028). On Kaplan-Meier analysis Bosniak 3s cysts were more likely to regress while Bosniak 3n cysts were more likely to progress than 3s cysts (p = 0.0178 and 0.0002, respectively). The growth rate of 3n and 2F cysts was 0.19 and 0.11 cm per year (p = 0.0493 and 0.0327, respectively). Locally advanced or metastatic disease did not develop in any patient. CONCLUSIONS: A diagnostic change in Bosniak 3s and 2F cysts is common and Bosniak 3n cysts behave more like Bosniak 4 cysts. Most complex kidney cysts can be safely monitored without intervention and the interval between serial imaging procedures should be increased.

Describing perspectives of health care professionals on active surveillance for the management of prostate cancer.

BACKGROUND: Over the last decade, active surveillance has proven to be a safe approach for patients with low-risk prostate cancer. Although active surveillance presents several advantages for both patients and the health care system, all eligible patients do not adopt this approach. Our goal was to evaluate the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach. METHODS: Focus groups (n = 5) were held with physicians who provided care for men with low-risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of health care professionals (HCPs) was captured to understand their decisions in proposing active surveillance and to reveal the barriers and facilitators that affect the adherence to this approach. A content analysis was performed on the verbatim transcripts from the sessions. RESULTS: Although physicians agreed that active surveillance is a suitable approach for low-risk prostate cancer patients, they were concerned about the rapidly evolving and non-standardized guidelines for patient follow-up. They pointed out the need for additional tools to appropriately identify proper patients for whom active surveillance is the best option. Urologists and radiation-oncologists were keen to collaborate with each other, but the role of general practitioner remained controversial once patients were referred to a specialist. CONCLUSIONS: Integration of more reliable tools and/or markers in addition to more specific guidelines for patient follow-up would increase the confidence of both patients and physicians in the choice of active surveillance.

Surveillance guidelines based on recurrence patterns for upper tract urothelial carcinoma.

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) accounts for 5% of all urothelial tumours. Due to its rarity, evidence regarding postoperative surveillance is lacking. The objective of this study was to develop a post-radical nephroureterectomy (RNU) surveillance protocol based on recurrence patterns in a large, multi-institutional cohort of patients. METHODS: Retrospective clinical and pathological data were collected from 1029 patients undergoing RNU over a 15-year period (1994-2009) at 10 Canadian academic institutions. A multivariable model was used to identify prognostic clinicopathological factors, which were then used to define risk categories. Risk-based surveillance guidelines were proposed based on actual recurrence patterns. RESULTS: Overall, 555 (49.9%) patients developed recurrence, including 289 (25.9%) in the urothelium and 266 (23.9%) with loco-regional and distant recurrences. Based on multivariable analysis, three risk groups were identified: 1) low-risk patients with pTa-T1, pN0 disease, and no adverse histological features (high tumour grade, lymphovascular invasion [LVI], tumour multifocality); 2) intermediate-risk patients with pTa-T1, pN0 disease with one or more of the adverse histological features; and 3) high-risk patients with a ≥pT2 tumour and/or nodal involvement. Low-, intermediate-, and high-risk patients were free of urothelial recurrence at three years in 72%, 66%, and 63%, respectively, and free of regional/distant recurrence in 93%, 87%, and 62%, respectively. The risks of loco-regional and distant recurrences (p<0.0001) and time to death (p<0.0001) were significantly different between the low-, intermediate-, and high-risk patients. CONCLUSIONS: Based on recurrence patterns in a large, multicentre patient cohort, we have proposed an evidence-based, risk-adapted post-RNU surveillance protocol.