Christian Seitz

Impact of Distal Ureter Management on Oncologic Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

BACKGROUND There is a lack of consensus regarding the optimal approach to the bladder cuff during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). OBJECTIVES To compare the oncologic outcomes following RNU using three different methods of bladder cuff management. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 2681 patients treated with RNU for UTUC at 24 international institutions from 1987 to 2007. INTERVENTION Three methods of bladder cuff excision were performed: transvesical, extravesical, and endoscopic. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable models tested the effect of distal ureter management on intravesical recurrence, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS Of the 2681 patients, 1811 (67.5%) underwent the transvesical approach; 785 (29.3%), the extravesical approach; and 85 (3.2%), the endoscopic approach. There was no difference in terms of RFS, CSS, and OS among the three distal ureteral management approaches. Patients who underwent the endoscopic approach were at significantly higher risk of intravesical recurrence compared with those who underwent the transvesical (p=0.02) or extravesical approaches (p=0.02); the latter two groups did not differ from each other (p=0.40). Actuarial intravesical RFS estimates at 2 and 5 yr after RNU were 69% and 58%, 69% and 51%, and 61% and 42% for the transvesical, extravesical, and endoscopic approaches, respectively. In multivariate analyses, distal ureteral management (p=0.01), surgical technique (open vs laparoscopic; p=0.02), previous bladder cancer (p<0.001), higher tumor stage (trend; p=0.01), concomitant carcinoma in situ (CIS) (p<0.001), and lymph node involvement (trend; p<0.001) were all associated with intravesical recurrence. Excluding patients with history of previous bladder cancer, all variables remained independent predictors of intravesical recurrence. CONCLUSIONS The endoscopic approach was associated with higher intravesical recurrence rates. Interestingly, concomitant CIS in the upper tract is a strong predictor of intravesical recurrence after RNU. The association of laparoscopic RNU with intravesical recurrence needs to be further investigated.

A Multinational, Multi-institutional Study Comparing Positive Surgical Margin Rates Among 22 393 Open, Laparoscopic, and Robot-assisted Radical Prostatectomy Patients

BACKGROUND Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and volume. OBJECTIVE To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates. DESIGN, SETTING, AND PARTICIPANTS Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort. RESULTS AND LIMITATIONS Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery in many of the open cohort cases; lack of standardized histologic processing and central pathology review; and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and individual surgeon caseload. CONCLUSIONS This multinational, multi-institutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases. PATIENT SUMMARY In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.

Prediction of 90-day Mortality After Radical Cystectomy for Bladder Cancer in a Prospective European Multicenter Cohort

BACKGROUND Despite recent improvements, radical cystectomy (RC) is still associated with adverse rates for 90-d mortality. OBJECTIVE To validate the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters. DESIGN, SETTING, AND PARTICIPANTS Data of 679 bladder cancer (BCa) patients treated with RC at 18 institutions in 2011 were prospectively collected, from which 597 patients were eligible for final analysis. INTERVENTION RC for BCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS An established prediction tool, the Isbarn nomogram, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver operating characteristics-derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities. Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality. RESULTS AND LIMITATIONS The 30-, 60-, and 90-d mortality rates in the development cohort (n=597) were 2.7%, 6.7%, and 9.0%, respectively. The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6%. Our preoperative multivariable model identified age (odds ratio [OR]:1.052), American Society of Anesthesiologists score (OR: 2.274), hospital volume (OR: 0.982), clinically lymphatic metastases (OR: 4.111), and clinically distant metastases (OR: 7.788) (all p<0.05) as independent predictors of 90-d mortality (predictive accuracy: 78.8%). Our conclusions are limited by the lack of an external validation of the preoperative model. CONCLUSIONS The Isbarn nomogram was validated with moderate discrimination. Our newly developed model consisting of preoperative characteristics might outperform existing models. Our model might be particularly suitable for preoperative patient counseling. PATIENT SUMMARY The current report validated an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy (RC). We developed a new prediction tool consisting of strictly preoperative parameters, thus allowing clinicians an optimal consultation for RC candidates.

Epidemiological gender-specific aspects in urolithiasis

PurposeThe incidence of urolithiasis is worldwide increasing and contributes to a rising economic and health care burden. The objective of this review is to identify gender differences in urolithiasis epidemiology in Europe and the USA as well as gender-specific risk factors for urolithiasis.Evidence acquisitionA systematic review of the present literature was performed including English journals without a time limit. The MeSH terms used were as follows: (“Sex Characteristics”[Mesh]) AND “Urolithiasis”[Mesh] or (“Epidemiology”[Mesh]) AND “Urolithiasis”[Mesh]. Additionally, reference search of retrieved papers identified additional references. The MEDLINE database was searched.Evidence synthesisThe prevalence of urolithiasis is rising worldwide including both genders in different age groups. Especially women face an increase in prevalence in the USA. Overweight seems to be an important cause for this development. Additionally insulin resistance and hypertonia, conditions present in the metabolic syndrome complex, contribute to this phenomenon.ConclusionStone prevalence across all age groups and both genders is increasing. Lifestyle changes along with increasing prevalence of obesity are key factors for this development. Female gender did significantly differ in the risk ratio of stone development in different variables including body mass index, hyperinsulinemia, and hypertension. It is important to inform the public on measures how to change lifestyle and dietary measures for preventing or lowering events of stone disease.

Association of Cigarette Smoking and Smoking Cessation with Biochemical Recurrence of Prostate Cancer in Patients Treated with Radical Prostatectomy

BACKGROUND Cigarette smoking seems to be associated with prostate cancer (PCa) incidence and mortality. OBJECTIVE To elucidate the association between pretreatment smoking status, cumulative smoking exposure, and time since smoking cessation and the risk of biochemical recurrence (BCR) of PCa in patients treated with radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 6538 patients with pathologically node-negative PCa treated with RP between 2000 and 2011. Clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation were collected. INTERVENTION RP without neoadjuvant therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable Cox regression analyses assessed the association between smoking and risk of PCa BCR. RESULTS AND LIMITATIONS Of 6538 patients, 2238 (34%), 2086 (32%), and 2214 (34%) were never, former, and current smokers, respectively. Median follow-up for patients not experiencing BCR was 28 mo (interquartile range 14-42). RP Gleason score (p=0.3), extracapsular extension (p=0.2), seminal vesicle invasion (p=0.8), and positive surgical margins (p=0.9) were comparable among the three groups. In multivariable Cox regression analysis, former smokers (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.30-2.04; p<0.001) and current smokers (HR 1.80, 95% CI 1.45-2.24; p<0.001) had a higher risk of PCa BCR compared with non-smokers. Smoking cessation for ≥10 yr mitigated the risk of BCR in multivariable analyses (HR 0.96, 95% CI 0.68-1.37; p=0.84). In multivariable analysis, no significant association between cumulative smoking exposure and risk of BCR could be detected. Limitations of the study include the retrospective design and potential recall bias regarding smoking history. CONCLUSION Smoking seems to be associated with a higher risk of PCa BCR after RP. The effects of smoking appear to be mitigated by ≥10 yr of cessation. Smokers should be counseled regarding the detrimental effects of smoking on PCa prognosis. PATIENT SUMMARY We investigated the effect of smoking on the risk of prostate cancer recurrence in patients with treated with surgery. We found that former smokers and current smokers were at higher risk of cancer recurrence compared to patients who never smoked; the detrimental effect of smoking was mitigated after 10 yr or more of smoking cessation. We conclude that smokers should be counseled regarding the detrimental effects on prostate cancer outcomes.

Conditional Survival After Radical Nephroureterectomy for Upper Tract Carcinoma

BACKGROUND Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies. OBJECTIVE To assess the changes in 5-yr CS rates after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to determine how well-established prognostic factors evolve over time. DESIGN, SETTING, AND PARTICIPANTS We analysed data from 3544 patients treated with RNU at 15 international academic centres between 1989 and 2012. INTERVENTION RNU. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS Conditional intravesical recurrence-free (IVRFS), cancer-specific survival (CSS), and overall survival (OS) estimates were calculated using the Kaplan-Meier method. A multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality. RESULTS AND LIMITATIONS The 5-yr bladder cancer recurrence-free survival, CSS, and OS rates were 54.9%, 72.2%, and 62.6%, respectively. Given a 1-, 2-, 3-, and 4-yr survivorship, the 5-yr conditional OS rates improved to 65.2%, 69.3%, 71.5%, and 73.0%, respectively. The 5-yr CS improvement was primarily noted among surviving patients with advanced-stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS, whereas the impact of age and gender increased with survivorship. No survival benefit was noted regarding the adjuvant chemotherapy status. Findings were confirmed upon multivariable analyses. Tumour location, the presence of carcinoma in situ, and the type of bladder cuff excision were continuously predictive for IVRFS whatever the survivorship. A limitation is the retrospective design. CONCLUSIONS CS analysis demonstrates that the patient risk profile evolves during the post-RNU follow-up. The probability of survival markedly increases over time in patients having high-stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS. PATIENT SUMMARY In this study, we found that the risk of intravesical recurrence, cancer-specific survival, and overall mortality evolves over the follow-up after surgery. Taking into account the survivorship provides better estimates of the survival probability at each follow-up time.

Effect of ABO blood type on mortality in patients with urothelial carcinoma of the bladder treated with radical cystectomy

OBJECTIVE ABO blood type is an inherited characteristic that has been associated with the prognosis of several malignancies, but there is little evidence in urothelial carcinoma of the bladder (UCB). The purpose of this study was to evaluate the effect of ABO blood type on mortality in patients with UCB treated with radical cystectomy (RC). METHODS Multi-institutional data from 7,906 patients with UCB treated with RC between 1979 and 2012 were retrospectively analyzed. The effect of ABO blood type on UCB-related mortality was evaluated with univariable and multivariable competing-risks regression models. RESULTS ABO blood type was O in 3,728 (47%), A in 2,748 (35%), B in 888 (11%), and AB in 532 (7%) patients. Blood type B was associated with a greater likelihood of lymphovascular invasion (P = 0.010) and positive soft tissue margins (P = 0.008). The median follow-up was 41 months. The 5-year cumulative UCB-related mortality rates for blood type O, A, B, and AB were 29.5%, 30.5%, 33.2%, and 25.8%, respectively. In univariable competing-risks regression, patients with blood type B had worse UCB-related mortality than those with blood type O (P = 0.026) and AB (P = 0.020). In multivariable analysis, however, blood type lost its statistical significance. CONCLUSIONS Among patients treated with RC, ABO blood type is associated with a statistically significant but clinically insignificant difference in UCB-related mortality. This association was not present in multivariable analysis. Our data therefore suggest no relevant association of ABO blood type with UCB-related prognosis.

Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy

To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on intravesical recurrence (IVR) outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Unenhanced MDCT in Patients with Suspected Urinary Stone Disease: Do Coronal Reformations Improve Diagnostic Performance?

OBJECTIVE The objectives of our study were to assess whether coronal reformations improve the diagnostic performance of MDCT in patients with acute flank pain and suspected urinary stone disease; and to determine if performing such reformations from 3-mm-thick sections is sufficient or if it is necessary to perform reformations from thinner sections. MATERIALS AND METHODS We included 147 consecutive patients (72 women and 75 men; mean age +/- SD, 58 +/- 18.1 years) with suspected urinary stone disease who underwent unenhanced MDCT. Scans were obtained with a 4 x 1 mm collimation and were reconstructed with a section thickness of 1.25 and 3 mm. We compared the diagnostic yield of 3-mm axial sections with that of coronal reformations reconstructed from 1.25- and 3-mm axial sections. Imaging data were evaluated in random order by two radiologists. The significance of the difference between the axial sections and coronal multiplanar reformations (MPRs) was tested for the number, size, and location of uroliths and for the presence of alternative diagnoses. The time required for review by both observers was recorded. RESULTS We found uroliths in 72 patients. There was no difference between 3-mm axial sections and coronal reformations from 1.25-mm sections with regard to the number of detected stones (n = 264 for both protocols), whereas coronal reformations from 3-mm sections revealed significantly fewer calcifications (n = 255, p = 0.016). Coronal reformations did not improve the localization of calcifications. Review time, however, was significantly shorter for coronal reformations than for axial sections (p = 0.001); however, coronal reformations were less sensitive than axial sections for the detection of additional findings suggestive of alternative diagnoses in 16 (30%) of 53 patients. CONCLUSION Coronal reformations from MDCT do not improve urinary stone detection but may reduce evaluation time; however, there is the danger of missing additional findings. Coronal reformations reconstructed from thick (i.e., 3-5 mm) axial sections may result in reduced detection of small stones and should therefore be avoided.

Validation of tertiary Gleason pattern 5 in Gleason score 7 prostate cancer as an independent predictor of biochemical recurrence and development of a prognostic model.

OBJECTIVE To validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5. MATERIAL AND METHODS We retrospectively reviewed the data from 4,146 patients with localized (pT2-3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model. RESULTS Of the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001). CONCLUSIONS Knowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling.