Antonio Finelli

Active Surveillance of Small Renal Masses: Progression Patterns of Early Stage Kidney Cancer ☆

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.

'Prostatic evasive anterior tumours': the role of magnetic resonance imaging.

Study Type – Diagnosis (case series)
Level of Evidence 4

Prevalence of Prostate Cancer on Autopsy: Cross-Sectional Study on Unscreened Caucasian and Asian Men

BACKGROUND Substantial geographical differences in prostate cancer (PCa) incidence and mortality exist, being lower among Asian (ASI) men compared with Caucasian (CAU) men. We prospectively compared PCa prevalence in CAU and ASI men from specific populations with low penetrance of prostate-specific antigen screening. METHODS Prostate glands were prospectively obtained during autopsy from men who died from causes other than PCa in Moscow, Russia (CAU), and Tokyo, Japan (ASI). Prostates were removed en-block and analyzed in toto. We compared across the 2 populations PCa prevalence, number and Gleason score (GS) of tumour foci, pathological stage, spatial location, and tumor volume using χ(2), Mann-Whitney-Wilcoxon tests, and multiple logistic regression. All statistical tests were two-sided. RESULTS Three hundred twenty prostates were collected, 220 from CAU men and 100 from ASI mean. The mean age was 62.5 in CAU men and 68.5 years in ASI men (P < .001). PCa prevalences of 37.3% in CAU men and 35.0% in ASI men were observed (P = .70). Average tumor volume was 0.303cm(3). In men aged greater than 60 years, PCa was observed in more than 40% of prostates, reaching nearly 60% in men aged greater than 80 years. GS 7 or greater cancers accounted for 23.1% and 51.4% of all PCa in CAU and ASI men, respectively, (P = .003). When adjusted for age and prostate weight, ASI men still had a greater probability of having GS 7 or greater PCa (P = .03). CONCLUSIONS PCa is found on autopsy in a similar proportion of Russian and Japanese men. More than 50% of cancers in ASI and nearly 25% of cancers in CAU men have a GS of 7 or greater. Our results suggest that the definition of clinically insignificant PCa might be worth re-examining.

Evidence for a biopsy derived grade artifact among larger prostate glands.

PURPOSE The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume. MATERIALS AND METHODS We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume. RESULTS Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade. CONCLUSIONS These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.

Unintended Consequences of Laparoscopic Surgery on Partial Nephrectomy for Kidney Cancer

PURPOSE Recent evidence suggests that partial nephrectomy may be associated with improved survival compared to radical nephrectomy for renal cell carcinoma but partial nephrectomy may be underused. We examined whether the introduction of laparoscopic radical nephrectomy contributed to low partial nephrectomy use with time. MATERIALS AND METHODS We identified all patients treated surgically for renal cell carcinoma in Ontario, Canada between 1995 and 2004 using the Ontario Cancer Registry, a population based tumor registry. A multinomial logistic regression model was used to relate the relative numbers of patients with open and laparoscopic radical nephrectomy, and partial nephrectomy to patient age, gender and surgery year. The partial nephrectomy time trend was investigated by fitting a segmented regression model. RESULTS Of 7,830 surgically treated patients 7,042 (89.9%) vs 788 (10.1%) underwent radical vs partial nephrectomy. Segmented regression showed a clear change in partial nephrectomy use with time (p = 0.001), such that the odds of partial nephrectomy increased by 18% per year before January 2003 (OR 1.18, 95% CI 1.14-1.23) and subsequently decreased by 12% per year (OR 0.88, 95% CI 0.75-1.02). In the multinomial regression model age and surgery year but not gender were independently associated with partial nephrectomy. CONCLUSIONS Partial nephrectomy use for renal cell carcinoma remains low, particularly in elderly patients. The introduction of laparoscopic radical nephrectomy coincided with decreased uptake and use of partial nephrectomy for renal cell carcinoma. Although it was hypothesized previously, to our knowledge this is the first study to suggest that the introduction of laparoscopy in renal surgery has negatively impacted partial nephrectomy use.

International Urology Journal Club via Twitter: 12-Month Experience

BACKGROUND Online journal clubs have increasingly been utilised to overcome the limitations of the traditional journal club. However, to date, no reported online journal club is available for international participation. OBJECTIVE To present a 12-mo experience from the International Urology Journal Club, the worlds first international journal club using Twitter, an online micro-blogging platform, and to demonstrate the viability and sustainability of such a journal club. DESIGN, SETTING, AND PARTICIPANTS #urojc is an asynchronous 48-h monthly journal club moderated by the Twitter account @iurojc. The open invitation discussions focussed on papers typically published within the previous 2-4 wk. Data were obtained via third-party Twitter analysis services. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Outcomes analysed included number of total and new users, number of tweets, and qualitative analysis of the relevance of tweets. Analysis was undertaken using GraphPad software, Microsoft Excel, and thematic qualitative analysis. RESULTS AND LIMITATIONS The first 12 mo saw a total of 189 unique users representing 19 countries and 6 continents. There was a mean of 39 monthly participants that included 14 first-time participants per month. The mean number of tweets per month was 195 of which 62% represented original tweets directly related to the topic of discussion and 22% represented retweets of original posts. A mean of 130 832 impressions, or reach, were created per month. The @iurojc moderator account has accumulated >1000 followers. The study is limited by potentially incomplete data extracted by third-party Twitter analysers. CONCLUSIONS Social media provides a potential for enormous international communication that has not been possible in the past. We believe the pioneering #urojc is both viable and sustainable. There is unlimited scope for journal clubs in other fields to follow the example of #urojc and utilise online portals to revitalise the traditional journal club while fostering international relationships.

Complications of Laparoscopic Surgery for Renal Masses: Prevention, Management, and Comparison with the Open Experience

CONTEXT The initial excitement about the laparoscopic treatment of renal masses has been tempered by concerns related to increased operative time, technical complexity, and the suitability of laparoscopic approaches to oncologic surgery. OBJECTIVE To provide a comprehensive review of intraoperative and postoperative complications and their prevention and management during laparoscopic surgery of renal tumors. EVIDENCE ACQUISITION A literature review of the Medline and Google Scholar databases was performed, searching for renal cell carcinoma, renal mass, laparoscopy, laparoscopic radical nephrectomy, open radical nephrectomy, laparoscopic partial nephrectomy, open partial nephrectomy, laparoscopic cryoablation, laparoscopic radiofrequency ablation, complications, intra-operative, and post-operative. English-language articles published between 1990 and 2008 were reviewed. EVIDENCE SYNTHESIS Laparoscopic radical nephrectomy (LRN), whether transperitoneal or retroperitoneal, can be performed safely. The overall complication rate is low and does not significantly differ from that of the open experience. Laparoscopic partial nephrectomy (LPN), in contrast, is a technically challenging procedure. Although the intermediate oncologic outcomes are comparable to those of the open experience, there are concerns related to warm ischemia time, and there is a risk of major complications such as urinary leakage and hemorrhage requiring transfusion. Laparoscopic-assisted ablative therapies (cryotherapy and radiofrequency) are being performed more commonly for the treatment of small exophytic renal lesions with a low complication rate and intermediate oncologic outcomes similar to LRN and LPN. CONCLUSIONS Complications associated with the laparoscopic management of renal masses vary among the different procedures and with surgeon experience. The rate of complication appears to be similar to that of open surgery.

Renal Tumor Biopsy for Small Renal Masses: A Single-center 13-year Experience

BACKGROUND Renal tumor biopsy (RTB) for the characterization of small renal masses (SRMs) has not been widely adopted despite reported safety and accuracy. Without pretreatment biopsy, patients with benign tumors are frequently overtreated. OBJECTIVE To assess the diagnostic rate of RTBs, to determine their concordance with surgical pathology, and to assess their impact on management. DESIGN, SETTING, AND PARTICIPANTS This is a single-institution retrospective study of 529 patients with biopsied solid SRMs ≤4 cm in diameter. RTBs were performed to aid in clinical management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Diagnostic and concordance rates were presented using proportions. Factors that contributed to a diagnostic biopsy were identified using a multivariable logistic regression. RESULTS AND LIMITATIONS The first biopsy was diagnostic in 90% (n=476) of cases. Of the nondiagnostic biopsies, 24 patients underwent a second biopsy of which 83% were diagnostic. When both were combined, RTBs yielded an overall diagnostic rate of 94%. Following RTB, treatment could have been avoided in at least 26% of cases because the lesion was benign. Tumor size and exophytic location were significantly associated with biopsy outcome. RTB histology and nuclear grade were highly concordant with final pathology (93% and 94%, respectively). Adverse events were low (8.5%) and were all self-limited with the exception of one. Although excellent concordance between RTB and final pathology was observed, only a subset of patients underwent surgery following biopsy. Thus it is possible that some patients were misdiagnosed. CONCLUSIONS RTB of SRMs provided a high rate of diagnostic accuracy, and more than a quarter were benign. Routine RTB for SRMs informs treatment decisions and diminishes unnecessary intervention. Our results support its systematic use and suggest that a change in clinical paradigm should be considered. PATIENT SUMMARY Renal tumor biopsy (RTB) for pretreatment identification of the pathology of small renal masses (SRMs) is safe and reliable and decreases unnecessary treatment. Routine RTB should be considered in all patients with an indeterminate SRM for which treatment is being considered.

Immediate Post–Transurethral Resection of Bladder Tumor Intravesical Chemotherapy Prevents Non–Muscle-invasive Bladder Cancer Recurrences: An Updated Meta-analysis on 2548 Patients and Quality-of-Evidence Review

CONTEXT Non-muscle-invasive bladder cancer (NMIBC) commonly recurs, requiring invasive and costly transurethral resection of bladder tumor (TURBT). A meta-analysis of seven trials published in 2004 demonstrated that intravesical chemotherapy (IVC) following TURBT reduces recurrences. Despite European Association of Urology endorsement, adoption of this practice has been modest. OBJECTIVE To investigate whether immediate postoperative IVC prolongs the recurrence-free interval (RFI) and early recurrences (ERs) in light of new trial data and to explore the quality of evidence supporting its use. EVIDENCE ACQUISITION A systematic literature review of random controlled trials (RCTs) published before March 2013 was performed using the Medline, Embase, and Cochrane databases. Trials examining NMIBC recurrence for adults receiving IVC immediately following TURBT were included. RFI was estimated by hazard ratio (HR), and ER was estimated by absolute risk reduction (ARR) of recurrences within 1 yr of TURBT. Both outcomes were synthesized using random-effects models. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool, and quality of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. EVIDENCE SYNTHESIS Thirteen studies with 2548 patients were included. IVC prolonged RFI by 38% (HR: 0.62; 95% confidence interval [CI], 0.50-0.77; p<0.001; I(2): 69%), and ERs were 12% less likely in the intervention population (ARR: 0.12; 95% CI, -0.18 to -0.06; p<0.001, I(2): 0%). The number needed to treat to prevent one ER was 9 (95% CI, 6-17 patients). There was high risk of bias present in 12 of 13 publications. Quality of evidence for RFI was very low and low for ERs. CONCLUSIONS Our updated meta-analysis supports that IVC prolongs RFI and reduces ERs of NMIBC when administered immediately after TURBT. However, contemporary methodology suggests low evidence quality for examined outcomes. Thus RCTs with careful randomization and blinding are still warranted to clarify the usefulness of immediate postoperative IVC in this population.

Optimal Management of High-Risk T1G3 Bladder Cancer: A Decision Analysis

Background Controversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3) bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE) and quality-adjusted life expectancy (QALE) for both of these treatments for men and women of different ages and comorbidity levels. Methods and Findings We evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1) Immediate cystectomy with neobladder creation versus (2) conservative management with intravesical bacillus Calmette-Guérin (BCG) and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients over the age of 70 y or those strongly averse to loss of sexual function, gastrointestinal dysfunction, or life without a bladder have a higher QALE with conservative therapy. The results of structural or probabilistic sensitivity analyses did not change the preferred treatment option. Model-predicted overall and disease-specific survival rates were similar to those reported in published studies, suggesting external validity. Conclusions Our model is, to our knowledge, the first of its kind in bladder cancer, and demonstrated that younger patients with high-risk T1G3 bladder had a higher LE and QALE with immediate cystectomy. The decision to pursue immediate cystectomy versus conservative therapy should be based on discussions that consider patient age, comorbid status, and an individuals preference for particular postcystectomy health states. Patients over the age of 70 y or those who place high value on sexual function, gastrointestinal function, or bladder preservation may benefit from a more conservative initial therapeutic approach.