Abstract Introduction Although urinary cytology (C) is the most widely used noninvasive test for the detection and surveillance of bladder cancer (BC), it has poor sensitivity especially for ...low-grade tumors. We prospectively tested the performance of urine markers on patients with BC using C and 4 commercially available urinary marker tests: Hemoglobin Dipstick (H), BTA Stat (B), NMP22 BladderChek (N), and ImmunoCyt (I). Methods Urinary samples from 109 consecutive patients with BC were prospectively collected. All samples were tested using conventional C and available biomarkers. Prior and subsequent surgical specimen reports were examined, and sensitivity and specificity were calculated for each. Collected variables included patient demographics, date of urinary collection, type of specimen (voided, washing, or catheterized), surgical pathology, recurrence, and follow-up. Results Sensitivity values for each marker were as follows: C, 48% (16% for low-grade tumors and 84% for high-grade HG tumors); B, 61% (36% and 91%); H, 51% (38% and 66%); N, 58% (25% and 92%); and I, 62% (47% and 83%). Specificity results for each marker were as follows: C, 86%; B, 78%; H, 58%; N, 85%; and I, 79%. On multivariate analysis, higher stage (C and N) and HG disease (C, H, B, N, and I) were independent prognostic factors for improved test performance. When urinary markers were combined with C, sensitivity/specificity values for HG disease were as follows: C+H, 85%/57%; C+B, 91%/78%; C+N, 94%/84%; and C+I, 90%/78%. Conclusions Based on these data, C seems to yield the highest specificity and N the highest sensitivity for HG tumors. The combination “C+N” seems to be the better approach to improve the sensitivity for HG tumors compared with single markers and other combinations.
Abstract Background Most early stage kidney cancers are renal cell carcinomas (RCCs), and most are diagnosed incidentally by imaging as small renal masses (SRMs). Indirect evidence suggests that most ...small RCCs grow slowly and rarely metastasize. Objective To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology. Design, setting, and participants A multicenter prospective phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and/or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression. Intervention Patients underwent serial imaging and needle core biopsies. Measurements We measured rates of change in tumor diameter (growth measured by imaging) and progression to ≥4 cm, doubling of tumor volume, or metastasis with histology on biopsy. Results and limitations Local progression occurred in 25 patients (12%), plus 2 progressed with metastases (1.1%). Of the 178 subjects with 209 SRMs, 127 with 151 SRMs had > 12 mo of follow-up with two or more images, with a mean follow-up of 28 mo. Their tumor diameters increased by an average of 0.13 cm/yr. Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate. Limitations included no central review of imaging and pathology and a short follow-up. Conclusions This is the first SRM active surveillance study to correlate growth with histology prospectively. In the first 2 yr, the rate of local progression to higher stage is low, and metastases are rare. SRMs appear to grow very slowly, even if biopsy proven to be RCC. Many patients with SRMs can therefore be initially managed conservatively with serial imaging, avoiding the morbidity of surgical or ablative treatment.
Objective To determine the oncological impact of pathological upstaging among patients with clinical T1 (cT1) disease treated by partial nephrectomy or radical nephrectomy. Methods The Canadian ...Kidney Cancer Information System comprises a prospectively maintained multi-institutional database for patients with renal cell carcinoma. Nonmetastatic, cT1 renal cell carcinoma cases were evaluated. Upstaging was defined as pathological T3a disease. Multivariate Cox regression analysis identified predictors for recurrence (local recurrence and/or metastatic disease) whereas logistic regression identified predictors of pathological upstaging. Kaplan-Meier methods estimated survival. Results Of 1448 eligible cT1 patients, upstaging was observed in 134 (9%). One thousand fifty-eight (73%) were treated by partial nephrectomy. After a median follow-up of 23 months, the 3-year recurrence-free survival was 76% in upstaged patients compared with 93% in those not upstaged ( P < .001). Controlling for age, gender, year of surgery, histology, tumor size, surgical approach, and margin status, pathological upstaging was independently associated with disease recurrence (hazard ratio 2.03, 95% confidence interval CI 1.12-3.68). Increasing age (odds ratio OR 1.02, 95% CI 1.00-1.05), Fuhrman grade (OR 2.47, 95% CI 1.47-4.14), and tumor size (OR 1.16, 95% CI 1.00-1.36) were independently associated with a risk of pathological upstaging. Conclusion Pathological upstaging confers a negative prognosis and highlights the importance of accurate clinical staging. A number of factors have been identified, including some attainable by renal biopsy, which may predict upstaging and provide valuable adjunct information to inform risk stratification and management decisions among patients with cT1 renal masses.
Preoperative exercise and fitness are predictors of surgical recovery; however, little is known of the effect of preoperative exercise-based conditioning, known as prehabilitation, in this for men ...undergoing radical prostatectomy. Our study examined the feasibility and effects of prehabilitation on perioperative and postoperative outcomes in men undergoing radical prostatectomy.
This feasibility RCT compared prehabilitation (PREHAB) versus a control condition (CON) in 86 men undergoing radical prostatectomy. PREHAB consisted of home-based, moderate-intensity exercise prior to surgery. Both groups received a preoperative pelvic floor training regimen. Feasibility was assessed via rates of recruitment, attrition, intervention duration and adherence, and adverse events. Clinical outcomes included surgical complications, and length of stay. The following outcomes were assessed at baseline, prior to surgery, and 4, 12, and 26-weeks postoperatively: 6-min walk test (6MWT), upper-extremity strength, quality of life, psychosocial wellbeing, urologic symptoms, and physical activity volume.
The recruitment rate was 47% and attrition rates were 25% and 33% for PREHAB and CON, respectively. Adherence to PREHAB was 69% with no serious intervention-related adverse events. After the intervention and prior to surgery, PREHAB participants demonstrated less anxiety (P = 0.035) and decreased body fat percentage (P = 0.001) compared to CON. Four-weeks postoperatively, PREHAB participants had greater 6MWT scores of clinical significance compared to CON (P = 0.006). Finally, compared to CON, grip strength and anxiety were also greater in the PREHAB at 26-weeks (P = 0.022) and (P = 0.025), respectively.
While feasible and safe, prehabilitation has promising benefits to physical and psychological wellbeing at salient timepoints relative to radical prostatectomy.
Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate ...mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2. Modulation of these proteins in cancer cell lines alters the expression of pathways that are central to the disease and highlights RBPs as driving master regulators of RCC transcriptome. This study presents a framework for the screening of RBP activities based on computational modeling of mRNA stability programs in cancer and highlights the role of post-transcriptional gene dysregulation in RCC.
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•Computational modeling of mRNA stability programs suggests a role of RBPs in cancer•Dysregulation of these programs leads to perturbation of cancer-associated pathways•RBP modulation in cell lines partially mirrors the transcriptome remodelling in cancer
Perron et al. develop a computational approach that models the functional activity of RBPs in individual cancer samples by monitoring their associated RNA stability programs. Applying this method to renal cell carcinoma transcriptomes, the authors identify RBPs that enhance cancer-associated pathways including hypoxia and cell cycle.
Studies have suggested a positive association between bladder cancer (BC) outcome and comedication use, including nonsteroidal anti-inflammatory drugs (NSAID), metformin, and prednisone use. To ...validate these associations, we evaluated whether these medications were associated with clinical outcome in a Canadian cohort of BC patients.
This is a retrospective cohort study on BC patients undergoing radical cystectomy (RC) in Québec province in 2000-2015, as registered in the provincial health administration databases. Medication use was considered chronic when prescribed for ≥ 1 year. Overall (OS), disease-specific (DSS) and recurrence-free (RFS) survival were compared using multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, hospital and surgeon annual RC volume, neoadjuvant chemotherapy use, and type of bladder diversion, as well as mutual adjustment for concomitant comedication use (statins, NSAIDs, metformin, and prednisone).
Of 3742 patients included, 293, 420, and 1503 patients chronically used prednisone, metformin, and NSAIDs before surgery, respectively. In multivariable analyses, preoperative prednisone use was associated with improved OS (HR 0.67, 95%CI 0.55-0.82), DSS (HR 0.58, 95%CI 0.45-0.76), and RFS (HR 0.61, 95%CI 0.47-0.78). Patients who chronically used metformin preoperatively had a worse OS (HR 1.29, 95%CI 1.07-1.55), DSS (HR 1.38, 95%CI 1.10-1.72), and RFS (HR 1.41, 95%CI 1.13-1.74). Preoperative, chronic NSAID use was not significantly associated with all clinical outcomes, with adjusted HRs for OS, DSS, and RFS of 1.10 (95%CI 0.95-1.27), 1.24 (95%CI 1.03-1.48), and 1.22 (95%CI 1.03-1.45), respectively. Directionality of findings was similar when stratifying by comedication use in the year following surgery. Results were similar after propensity-score matching too.
In our Canadian cohort of BC undergoing RC, chronic prednisone use was associated with improved clinical outcomes, while metformin and NSAID were not.
Purpose
To determine how members of the Société Internationale d’Urologie (SIU) are continuing their education in the time of COVID-19.
Methods
A survey was disseminated amongst SIU members worldwide ...by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents.
Results
In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; all
p
s < 0.001), followed by searching journals and textbook including the online versions (62%; all
p
s < 0.001). Overall, 6% of the respondents reported no time/interest for CME during the pandemic. Although most urologists report using only one platform for their CME (26.6%), the majority reported using ≥ 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice.
Conclusion
During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods.
•This study compared outcomes in patients with clinically localized type 2 vs. 1 pRCC.•Type 2 pRCC was associated with elevated all-cause mortality (aHR: 7.7, P = 0.0027).•Type 2 pRCC was associated ...with worse recurrence-free survival (aHR: 8.2, P< 0.0001).•Pathologic stage, tumor diameter and nuclear grade was greater in type 2 pRCC.•Radical nephrectomy and lymphadenectomy was more commonly performed in type 2 pRCC.
To evaluate outcomes of surgically treated patients with clinically localized papillary renal cell carcinoma (RCC) and determine if papillary RCC subtype is associated with recurrence and survival.
This is a historical cohort study using the prospectively maintained Canadian Kidney Cancer Information System database between January 2011 and September 2018. All patients underwent partial or radical nephrectomy. Patient, tumor, treatment, and outcomes were compared between papillary RCC type 2 and type 1 cohorts.
During the study period, 509 patients had clinically localized papillary RCC type 2 (n = 172) or type 1 (n = 337) histology. Sex, race, and comorbidities were similar between groups. Pathologic stage (pT3 or pT4), nuclear grade (3 or 4), and tumor diameter were higher in the type 2 papillary RCC cohort (P < 0.0001). A greater proportion of type 2 papillary RCC patients received radical nephrectomy (42.4% vs. 24.6%, P< 0.0001). More type 2 papillary RCC patients underwent lymph node dissection (19.6% vs. 5.5%, P< 0.0001) and had lymph node metastases removed during surgery (6.4% vs. 0.6%, P= 0.103). Overall, adjusting for age, grade, pathologic stage, positive nodes, and tumor size, type 2 papillary RCC had worse outcomes compared to type 1, as demonstrated by elevated all-cause mortality (hazard ratio = 7.7 95% confidence interval: 2.0–28.9), P=0.0027) and worse recurrence-free survival (hazard ratio = 8.2 95% confidence interval: 3.6–19.0, P< 0.0001).
Patients with clinically localized type 2 papillary RCC present with higher risk disease and have worse prognosis compared to patients with clinically localized type 1 papillary RCC. To the best of our knowledge, this is the largest cohort study comparing papillary RCC subtypes.
Summary pT1 bladder urothelial carcinomas represent a heterogeneous group of tumors with different biologic behaviors, and identifying the subset of tumors that carries a high risk of disease ...recurrence and progression is therefore important. We evaluated the prognostic significance of substaging 86 cases of pT1 bladder urothelial carcinoma based on different pathologic parameters. The mean tumor depth was 1.1 mm, and the mean diameter of the invasive focus was 2.2 mm. The mean number of tissue fragments with invasion was 4.4. Lymphovascular invasion and concomitant carcinoma in situ were present in 13% and 45% of cases, respectively. Although 56% of patients recurred, 18% experienced disease progression. Multivariate analysis showed a significant association between muscularis mucosa invasion ( P = .007), depth of invasion ( P = .0001), diameter of invasive focus ( P = .014), and progression. Furthermore, depth of invasion more than 3 mm was significantly associated with progression of disease, achieving a sensitivity of 31%, specificity of 99%, and predictive value of 79%. In comparison, the cutoff values for the diameter of invasive carcinoma that correlated best with outcome was 6 mm for progression. Lastly, combining both variables showed a strong prognostic accuracy where it predicted 94% of recurrences. Importantly, all cases with depth of invasion more than 3 mm and diameter more than 6 mm progressed. Lymphovascular invasion or concomitant carcinoma in situ did not correlate with outcome. From the current data, we do recommend reporting muscularis mucosa invasion whenever possible. Alternatively, tumor depth and tumor diameter should be included in the final pathology report in individual cases in which muscularis mucosa invasion cannot be assessed.
Abstract Although differentiating reactive urothelial atypia from urothelial carcinoma in situ (CIS) relies primarily on histologic evaluation, confirming the morphologic impression using ...immunohistochemistry (IHC) has been increasingly used in routine clinical practice. The aims of this study are to confirm the utility of commonly used markers (CK20, P53) and to test the performance of CK5/6, CD138, and Her2/Neu in the diagnosis of CIS. Using a tissue microarray comprising 52 cases of normal/reactive urothelium and 45 cases of CIS, the IHC evaluation of 5 markers was undertaken. Although the individual specificity of CK20, P53, and Her2/Neu was high (94%, 90%, and 93%, respectively), their sensitivity for CIS detection was lower, with the most sensitive marker being HER2/Neu (63%). Whereas 78% of CIS shows positivity of at least 2 of those 3 markers, only 1 case of reactive urothelium shows positivity for 2 of those 3 markers. The discriminatory performance of CK5/6 and CD138 was poor. In conclusion, HER2/Neu can be added to a panel of CK20 and P53 to help differentiate reactive atypia from CIS in difficult cases. Positive staining for at least 2 of the 3 antibodies (CK20, P53, and HER2/Neu) is strongly associated with CIS. However, the histologic findings should be a primary determinant in the diagnosis of flat urothelial lesions, with IHC playing a supportive confirmatory role.
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