Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.     

Prospective Evaluation of a Molecular Marker Panel for Prediction of Recurrence and Cancer-specific Survival After Radical Cystectomy

Background

Retrospective studies demonstrated that cell cycle–related and proliferation biomarkers add information to standard pathologic tumor features after radical cystectomy (RC). There are no prospective studies validating the clinical utility of markers in bladder cancer.

Objective

To prospectively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder (UCB) who were likely to experience disease recurrence or mortality.

Design, setting, and participants

Between January 2007 and January 2012, every patient with high-grade bladder cancer, including 216 patients treated with RC and lymphadenectomy, underwent immunohistochemical staining for tumor protein p53 (Tp53); cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); cyclin-dependent kinase inhibitor 1B (p27, Kip1); antigen identified by monoclonal antibody Ki-67 (MKI67); and cyclin E1.

Intervention

Every patient underwent RC and lymphadenectomy, and marker staining.

Outcome measurements and statistical analysis

Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality (CSM).

Results and limitations

Pathologic stage among the study population was pT0 (5%), pT1 (35%), pT2 (19%), pT3 (29%), and pT4 (13%); lymphovascular invasion (LVI) was seen in 34%. The median number of removed lymph nodes was 23, and 60 patients had lymph node involvement (LNI). Median follow-up was 20 mo. Expression of p53, p21, p27, cyclin E1, and Ki-67 were altered in 54%, 26%, 46%, 15%, and 75% patients, respectively. In univariable analyses, pT stage, LNI, LVI, perioperative chemotherapy (CTx), margin status, and number of altered biomarkers predicted disease recurrence. In a multivariable model adjusting for pathologic stage, margins, LNI, and adjuvant CTx, only LVI and number of altered biomarkers were independent predictors of recurrence and CSM. The concordance index of a baseline model predicting CSM (including pathologic stage, margins, LVI, LNI, and adjuvant CTx) was 80% and improved to 83% with addition of the number of altered markers.

Conclusions

Molecular markers improve the prediction of recurrence and CSM after RC. They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy.     

External validation of postoperative nomograms for prediction of all-cause mortality, cancer-specific mortality, and recurrence in patients with urothelial carcinoma of the bladder

Background

The Bladder Cancer Research Consortium (BCRC) created nomograms to predict all-cause mortality (ACM), cancer-specific mortality (CSM), and recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

Objective

To perform a formal validation of the BCRC nomograms in a large multi-institutional patient cohort from Europe.

Design, setting, and participants

Records of 2501 patients who underwent RC for UCB at eight European centers were reviewed. Complete information for external validation was available in 2404 patients for the ACM and CSM nomograms and in 2243 patients for the recurrence nomogram.

Measurements

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 at 2 yr, 5 yr, and 8 yr. Decision curve analyses were applied to assess the net benefit derived from the three models.

Results and limitations

The discrimination accuracies of the BCRC nomograms for ACM and CSM at 2 yr, 5 yr, and 8 yr after RC were 71.0%, 69.1%, and 68.2%, and 74.9%, 73.1%, and 72.4%, respectively. The accuracy of discrimination for the recurrence nomogram at the same time points was 76.5%, 75.3%, and 74.9%, respectively. Calibration plots revealed slight underestimations from ideal predictions. Decision curve analyses showed an increased net benefit for the use of the BCRC nomograms in this cohort. Limitations include the retrospective study design, potential surgeon bias, and lack of a central pathologic review.

Conclusions

The ACM, CSM, and recurrence nomograms showed acceptable predictive accuracies and could thus be adopted into clinical practice in UCB patients treated in Europe.     

A non-cancer-related survival benefit is associated with partial nephrectomy

Background

Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC).

Objective

Test the effect of treatment type on OCM.

Design, setting, and participants

Using the Surveillance Epidemiology and End Results–Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988–2005).

Measurements

To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancer-specific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery.

Results and limitations

Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69–0.98; p = 0.04). Increasing age (HR: 1.08, p < 0.001), higher CCI (HR: 1.14, p < 0.001), female gender (HR: 0.79, p = 0.02), baseline hypercalcemia (HR: 2.05, p = 0.03), baseline hyperlipidemia (HR: 0.73, p = 0.003), and year of surgery (HR: 0.95, p = 0.003) were independent predictors of OCM.

Conclusions

Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible.     

The Extent of Lymphadenectomy Seems to Be Associated with Better Survival in Patients with Nonmetastatic Upper-Tract Urothelial Carcinoma: How Many Lymph Nodes Should Be Removed?

Background

The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated.

Objective

To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC.

Design, setting, and participants

The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006.

Intervention

Patients were treated with RNU and lymphadenectomy.

Measurements

Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified.

Results and limitations

In the entire population, the number of LNs removed was not associated with CSM in univariable (hazard ratio [HR]: 0.99; p = 0.16) or in multivariable (HR: 0.97; p = 0.12) analyses. In contrast, in the subgroup of pN0 patients (n = 412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p = 0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p = 0.004). The inclusion of the variable defining dichotomously the number of removed LNs (<8 vs ≥8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p < 0.001).

Conclusions

The extension of the lymphadenectomy in pN0 UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed.     

Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort

Background

Management of T1 grade 3 (T1G3) urothelial carcinoma of the bladder (UCB), with its variable behaviour, represents one of the most difficult challenges for urologists and patients alike.

Objective

To evaluate the characteristics and long-term outcome of patients with clinical T1G3 UCB treated with radical cystectomy (RC).

Design, setting, and participants

Data from 1136 patients treated with RC for clinical T1G3 UCB without neoadjuvant chemotherapy were collected at 12 centres located in Europe, the United States, and Canada. Median age was 67 yr (range: 29–94), with a male-to-female ratio of 4:1.

Measurements

Patients’ characteristics and outcome are evaluated.

Results and limitations

Of the 1136 patients, 33.4% had non–organ-confined stage at cystectomy, and 16.2% had lymph node (LN) metastasis; 49.7% were upstaged after RC to muscle-invasive disease, while 21.4% were downstaged to lower than T1G3. Within a median follow-up of 48 mo, 35.5% of patients died of metastatic UCB.

Conclusions

Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle-invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC.     

Age,American Society of Anesthesiologists physical status classification and Charlson score are independent predictors of 90-day mortality after radical cystectomy

Purpose

Radical cystectomy (RC) is a major surgical procedure accompanied with meaningful complications and countable perioperative mortality. To identify the risk factors predicting the perioperative morbidity and mortality is essential. The study aimed to identify relevant, patient-specific factors associated with 90-day mortality following RC, which may serve as a foundation for improving healthcare delivery to patients with bladder cancer.

Methods

We investigated a sample of 1015 consecutive patients in order to identify predictors of 90-day mortality after RC. Beside tumor-related parameters, ASA classification, NYHA, Canadian Cardiovascular Society classification of angina pectoris, Charlson score, age, gender and the single conditions contributing to the Charlson score were included in the multivariable analyses. The patient data were collected retrospectively, except the ASA score that was obtained prospectively.

Results

We identified a model containing the parameters age (OR 1.05, p = 0.023), ASA classification of 3–4 (OR 6.19, p < 0.001) and Charlson score (OR 1.22, p = 0.003) to predict 90-day mortality. Among the single conditions to the Charlson score, moderate or severe renal disease (OR 3.94, p < 0.001) and liver disease (OR 3.24, p = 0.037) were most closely related to 90-day mortality.

Conclusions

Age, ASA classification and Charlson score as well as moderate or severe renal disease and liver disease appear to be independent predictors of 90-day mortality after RC. Given the highly significant association of ASA score with 90-day mortality and the relative ease and width disposability of this measure, this classification should be, after external validation, incorporated into daily clinical practice in treatment of patients planned to RC.

     

A competing-risks analysis of survival after alternative treatment modalities for prostate cancer patients: 1988-2006

Background

The efficacy of prostate cancer (PCa) treatment modalities is a subject of continuous debate.

Objective

We tested the hypothesis that significant differences in survival rates may exist among PCa patients treated with radical prostatectomy (RP), radiation therapy (RT), and observation.

Design, setting, and participants

We focused on 404 604 patients with clinically localized PCa within 17 Surveillance, Epidemiology and End Results registries.

Measurements

Competing-risks survival analyses were used to estimate cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. Patients were stratified according to treatment type, age group, and PCa risk group (high risk: T2c and/or Gleason score 8–10; low to intermediate risk: all others).

Results and limitations

The 10-yr CSM and OCM rates were 6.1% and 29.2%, respectively. In RP, RT, and observation patients, CSM rates were 3.6%, 6.5%, and 10.8% (p < 0.001), respectively; OCM rates were 17.1%, 32.4%, and 48.9% (p < 0.001), respectively. In low- to intermediate-risk patients, the lowest CSM (1.3–3.7%) and OCM (6.9–31.6%) rates within all age categories except octogenarians (8.9% and 62.8%, respectively) were recorded in RP. In high-risk patients, the lowest CSM (5.8–7.2%) and OCM (8.7–16.1%) rates in patients aged ≤69 yr were also recorded in RP. RT was equally favorable to RP in the 70–79 age category and appeared ideal in all octogenarian patients.

Conclusions

Our results showed that RP provides the most favorable survival rates in most patients. The exception is octogenarian men, in whom RT provides the best results. Finally, the least-favorable outcomes were recorded after observation. However, these findings must be interpreted within the context of the limitations of observational data.     

Are Infertile Men Less Healthy than Fertile Men? Results of a Prospective Case-Control Survey

Background

An association between either subfertility or infertility and an elevated risk of certain male cancers has been previously reported. Nothing is known about abnormalities in infertility and general health conditions.

Objective

To assess whether men with male factor infertility (MFI) are overall less healthy than fertile men, regardless of the reasons for infertility.

Design, setting, and participants

From September 2006 to September 2007, 344 consecutive European Caucasian men with MFI were enrolled in this prospective case-controlled study. Patients were compared with a control group of 293 consecutive age-comparable fertile men. Infertile men were consecutively attending the outpatient male reproductive clinic at a tertiary academic center. Fertile controls were consecutively recruited by use of advertisements posted within our hospital.

Measurements

Comorbidities of patients and fertile men were objectively scored with the Charlson Comorbidity Index (CCI) according to the International Classification of Diseases modified ninth version (ICD-9-CM) codes. Multivariate linear regression models tested the association between predictors and CCI score, as a proxy of general health status.

Results

According to the CCI scores, infertile men had a significantly higher rate of comorbidities compared with the fertile controls (CCI: 0.33 [0.8] vs 0.14 [0.5]; p < 0.001; 95% CI: 0.08–0.29). Linear regression analyses showed that although educational status did not have an impact on CCI (β: 0.035; p = 0.365), while CCI linearly increased with age (β: 0.196; p < 0.001) and body mass index (BMI; β: 0.161; p < 0.001). After adjusting for age, BMI, and educational status, a significantly lower CCI was calculated for fertile men and compared with MFI patients (β: −0.199; p < 0.001).

Conclusions

These results show that MFI accounts for a higher CCI, which may be considered a reliable proxy of a lower general health status.     

Observation Should be Considered as an Alternative in Management of Renal Masses in Older and Comorbid Patients

Background

Renal masses diagnosed in older and comorbid patients represent a challenge with regard to treatment.

Objective

To evaluate clinical outcome and tumor progression in patients with renal masses managed by observation due to age and comorbidity.

Design, setting, and participants

The medical records of 63 consecutive patients with renal masses primarily managed by observation during 2002–2007 were reviewed retrospectively and analyzed. The mean age for all patients at diagnosis was 76.6 yr, and 59% were male. Mean tumor size was 4.3 cm in diameter at diagnosis. Of these, 30% had Eastern Cooperative Oncology Group performance status (PS) of 2 or 3, 78% were American Society of Anesthesiologists (ASA) class 3, and the patients had a mean of 2.8 other medical conditions.

Measurements

Registration of age, ASA class, PS, comorbid conditions, computed tomography scans, primary tumor size, tumor growth rate, pathology parameters, observation time, survival time.

Results and limitations

Five-year overall survival (OS) and cancer-specific survival (CSS) rates were 42.8% and 93.3%, respectively. For tumors ≤4.0 cm in size, 5-yr CSS was 100%. Nine patients received delayed radical treatment, none of whom had later progression of the disease. In 18 patients histopathologic diagnosis of the renal masses were available, and in 15 patients (83%) renal cell carcinoma (RCC) was verified. The annual growth rate was <1 cm/yr in 85.4% of the cases. In tumors ≤4.0 cm, only 1 of 27 tumors (3.7%) grew faster than 1 cm/yr.

Conclusions

Management of renal masses by observation among older and comorbid patients seems to give acceptable results with regard to OS and CSS rates after 5 yr. The risk of disease progression is significantly higher in patients with larger sized renal masses (>4 cm). Thus, selection for observation in this group has to be stricter than in a group of patients with smaller sized renal masses (≤4.0 cm).     

Are Antisperm Antibodies Really Associated with Proven Chronic Inflammatory and Infectious Diseases of the Male Reproductive Tract?

Background

It is debated whether chronic urogenital inflammations and infections may trigger the formation of antisperm antibodies (ASA) in semen.

Objective

To evaluate the formation of ASA in defined chronic inflammatory and infectious diseases of the male reproductive tract (MRT).

Design, setting, and participants

Three hundred sixty-five patients retrospectively enrolled in a single center were categorized as having National Institutes of Health (NIH) category II chronic prostatitis (n = 38), NIH category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) (n = 59), NIH category IIIb CP/CPPS (n = 213), chronic epididymitis (n = 34), and chronic urethritis (n = 21). Forty-five age-matched men served as controls.

Measurements

All subjects underwent microbiologic and cytologic analysis for common bacteria, yeasts, and mycoplasma using the four-glass test. Urine samples, ejaculates, and urethral swabs were analyzed with polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria gonorrhea. Semen analysis followed World Health Organization (WHO) standards. ASA in seminal plasma were analyzed using the mixed agglutination reaction (MAR) test.

Results and limitations

The overall positive detection rate of clinically significant levels (≥50% of spermatozoa coated by ASA) of IgG and IgA antibodies was 1.8% and 0.8%, respectively, in the patient group. No clinically significant levels of ASA were detected in the control group, and no statistically significant difference was observed between controls and patients (IgG, p = 1.0; IgA, p = 1.0). No difference was found between the different inflammatory and infectious diseases and the control group in the detection rate of ASA, even when the cut-point value was lowered to ≥1% (IgG, p = 0.4; IgA, p = 0.3). Moreover, in one selected subgroup of patients (n = 26) with persistent increased inflammatory parameters (peroxidase-positive leukocytes [PPL] ≥1 × 10⁶/ml and elastase ≥230 ng/ml), no significant difference in the levels of ASA was observed compared with the controls (IgG, p = 0.1; IgA, p = 0.8).

Conclusion

There is no association between chronic inflammatory or infectious diseases of the MRT and the presence of ASA in semen.     

Anaesthetic preoperative assessment of chronic medications and herbal medicine use: a multicenter survey

Objective

This study was undertaken to quantify the use of chronic medication and herbal remedies in the presurgical population.

Study design

Prospective multicenter survey.

Patients and methods

Adult patients presenting for anaesthesia were directly asked if they were currently using chronic medication or herbal remedies.

Results

Among 1057 patients (age 54 ± 17 yrs, woman 54%, ASA 2 [1–4], 74%) were taking one or more chronic medication. The most commonly used treatments were, in descending order angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers (15%), beta blockers (11%) and platelet inhibitors (10%). Also, 9% were taking one or more of the following herbal remedies known to interact with the perioperative period: valeriane, ginseng, ginkgo, St John's wort, echinacea and ephedra. Women and patients aged 40-70 yr were most likely to be taking a herbal product (p < 0.001 and p < 0.01 respectively).

Conclusion

Chronic medication and herbal remedies are common in patients presenting for anaesthesia. Because of the potential interactions between anaesthetic drugs or techniques and such medication it is important for anaesthetists to be aware of their use.     

Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity

Background

The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear.

Objective

Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND).

Design, setting, and participants

A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo.

Intervention

RC with mapping PLND.

Measurements

We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression.

Results and limitations

Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04–3.46], p = 0.036; versus HR: 4.3 [95% CI, 2.25–8.34], p < 0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10–42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22–54] and 35% [95% CI, 11–60], respectively). This study is limited by the lack of prospective randomization and a control group.

Conclusions

The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.     

Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study

Background

Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB).

Objective

Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC in patients with clinically nonmetastatic UCB.

Design, setting, and participants

Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization.

Intervention

Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy.

Measurements

Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis.

Results and limitations

CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1–100). Presence, number, and HER2 status of CTC were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality (p values: ≤0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤0.003). HER2 was strongly positive in CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size.

Conclusions

Preoperative CTC are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials.     

Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome

Background

The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome.

Objective

Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients.

Design, setting, and participants

The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy.

Measurements

Patients’ characteristics and outcome were evaluated.

Results and limitations

The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p = 0.002 and p = 0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p = 0.011 and p = 0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes.

Conclusions

In this large international cohort, pathologic substaging helped to stratify patients with lymph node–negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging.     

Perioperative Morbidity of Laparoscopic Cryoablation of Small Renal Masses with Ultrathin Probes: A European Multicentre Experience

Background

Low morbidity has been advocated for cryoablation of small renal masses.

Objectives

To assess negative perioperative outcomes of laparoscopic renal cryoablation (LRC) with ultrathin cryoprobes and patient, tumour, and operative risk factors for their development.

Design, setting, and participants

Prospective collection of data on LRC in five centres.

Intervention

LRC.

Measurements

Preoperative morbidity was assessed clinically and the American Society of Anaesthesiologists (ASA) score was assigned prospectively. Charlson Comorbidity Index (CCI) and Charlson-Age Comorbidity Index (CACI) scores were retrospectively assigned. Negative outcomes were prospectively recorded and defined as any undesired event during the perioperative period, including complications, with the latter classed according to the Clavien system. Patient, tumour, and operative variables were tested in univariate analysis as risk factors for occurrence of negative outcomes. Significant variables (p < 0.05) were entered in a step-forward multivariate logistic regression model to identify independent risk factors for one or more perioperative negative outcomes. The confidence interval was settled at 95%.

Results and limitations

There were 148 procedures in 144 patients. Median age and tumour size were 70.5 yr (range: 32–87) and 2.6 cm (range: 1.0–5.6), respectively. A laparoscopic approach was used in 145 cases (98%). Median ASA, CCI, and CACI scores were 2 (range: 1–3), 2 (range: 0–7), and 4 (range: 0–11), respectively. Comorbidities were present in 79% of patients. Thirty negative outcomes and 28 complications occurred in 25 (17%) and 23 (15.5%) cases, respectively. Only 20% of all complications were Clavien grade ≥3. Multivariate analysis showed that tumour size in centimetres, the presence of cardiac conditions, and female gender were independent predictors of negative perioperative outcomes occurrence. Receiver operator characteristic curve confirmed the tumour size cut-off of 3.4 cm as an adequate predictor of negative outcomes.

Conclusions

Perioperative negative outcomes and complications occur in 17 % and 15.5%, respectively, of cases treated by LRC with multiple ultrathin needles. Most of the complications are Clavien grade 1 or 2. The presence of cardiac conditions, female gender, and tumour size are independent prognostic factors for the occurrence of a perioperative negative outcome.     

Laparoendoscopic single-site radical nephrectomy for renal cancer: technique and surgical outcomes

Background

Laparoendoscopic single-site (LESS) surgery has been developed in attempt to further reduce the morbidity and scarring associated with surgical intervention.

Objective

To describe the technique and report the surgical outcomes of LESS radical nephrectomy (RN) in the treatment of renal cell carcinoma.

Design, setting, and participants

LESS-RN was performed in 33 patients with renal tumours. The indications to perform a LESS-RN were represented by renal tumours not greater than T2 and without evidence of lymphadenopathy or renal vein involvement.

Surgical procedure

The Endocone (Karl Storz, Tuttlingen, Germany) was inserted through a transumbilical incision. A combination of standard laparoscopic instruments and bent grasper and scissors was used. The sequence of steps of LESS-RN was comparable to standard laparoscopic RN.

Measurements

Demographic data and perioperative and postoperative variables were recorded and analysed.

Results and limitations

The mean operative time was 143.7 ± 24.3 min, with a mean estimated blood loss of 122.3 ± 34.1 ml and a mean hospital stay of 3.8 ± 0.8 d. The mean length of skin incision was 4.1 ± 0.6 cm and all patients were discharged from hospital with minimal discomfort, as demonstrated by their pain assessment scores (visual analogue scale: 1.9 ± 0.8). The definitive pathologic results revealed a renal cell carcinoma in all cases and a stage distribution of four T1a, 27 T1b, and 2 T2 tumours. All patients were very satisfied with the appearance of the scars, and at a median follow-up period of 13.2 ± 3.9 mo, all patients were alive without evidence of tumour recurrence or port-site metastasis.

Conclusions

LESS is a safe and feasible surgical procedure for RN in the treatment of renal cell carcinoma and has excellent cosmetic results.     

Robotic versus laparoscopic partial nephrectomy for complex tumors: comparison of perioperative outcomes

Background

Recent studies showed that robotic partial nephrectomy (RPN) offered outcomes at least comparable to those of laparoscopic partial nephrectomy (LPN). LPN can be particularly challenging for more complex tumors.

Objective

To compare the perioperative outcomes of patients undergoing LPN or RPN for a single renal mass of moderate or high complexity.

Design, setting, and participants

A retrospective analysis was performed for 381 consecutive patients who underwent either LPN (n = 182) or RPN (n = 199) between 2005 and 2011 for a complex renal mass (RENAL score ≥7). Perioperative outcomes were compared. Predictors of postoperative renal function were assessed using multivariable linear regression analysis.

Intervention

LPN or RPN.

Outcome measurements and statistical analysis

Perioperative outcomes were compared. Predictors of postoperative renal function were assessed using multivariable linear regression analysis.

Results and limitations

There was no significant difference between the two groups with respect to patient age, gender, side, American Society of Anesthesiologists score, Charlson comorbidity index (CCI), or tumor size. Patients undergoing LPN had a slightly lower body mass index (29.2 kg/m² compared with 30.7 kg/m², p = 0.02) and preoperative estimated glomerular filtration rate (eGFR) (81.1 compared with 86.0 ml/min per 1.73 m², p = 0.02). LPN was associated with an increased rate of conversion to radical nephrectomy (RN) (11.5% compared with 1%, p < 0.001) and a higher decrease in percentage of eGFR (−16.0% compared with −12.6%, p = 0.03). There were no significant differences with respect to warm ischemia time (WIT), estimated blood loss, transfusion rate, or postoperative complications. WIT, preoperative eGFR, and CCI were found to be predictors of postoperative eGFR in multivariable analysis. No difference in perioperative outcomes was found between moderate and high RENAL score subgroups. The retrospective study design was the main limitation of this study.

Conclusions

RPN provides functional outcomes comparable to those of LPN for moderate- to high-complexity tumors, but with a significantly lower risk of conversion to RN. This situation is likely because of the technical advantages offered by the articulated robotic instruments. A prospective randomized study is needed to confirm these findings.     

Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience

Background

Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown.

Objective

Report long-term outcomes of patients with muscle-invasive BCa treated by CMT.

Design, setting, and participants

We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2–4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr.

Interventions

Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40 Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC—60 for less than CR and 42 for recurrent invasive tumors.

Measurements

Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method.

Results and limitations

Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2 = 74%, 67%, and 63%; T3–4 = 53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3–4 = 41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p < 0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity.

Conclusions

CMT achieves a CR and preserves the native bladder in >70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients.     

Effect of ephedrine on the intubation conditions using rocuronium versus succinylcholine

Objective

The goal of this study was to determine if ephedrine could improve intubating conditions when it is administered before the muscle relaxant (rocuronium and succinylcholine).

Patients and methods

In this prospective randomized double-blind study, 80 patients ASA I- II, scheduled for elective surgery, were allocated randomly to receive: succinylcholine 1 mg/kg + ephedrine 70 μg/kg (Group I, n = 20); rocuronium 0.6 mg/kg + ephedrine 70 μg/kg (Group II, n = 20); succinylcholine 1 mg/kg + 0.9% saline (Group III, n = 20); rocuronium 0.6 mg/kg + 0.9% saline (Group IV, n = 20). Induction of anaesthesia started with administration of the first syringe containing either ephedrine or saline, then 30 s later propofol 2.5 mg/kg and fentanyl 3 μg/kg, were administered followed by the contents of the second syringe containing either rocuronium or succinylcholine. Thirty seconds after injection of the muscle relaxant, another blinded staff anaesthetist performed intubation of the patient. Intubating conditions were evaluated according to criteria's of the conference of Copenhagen. Heart rate, systolic blood pressure and diastolic were also noted. Kruskall-Wallis test for non-parametric variable and Student t test for quantitative variables were used for statistical analysis.

Results

There was no significant difference between the groups concerning age, sex, BMI and ASA status. Pretreatment by ephedrine improved significantly (p < 0.0001) intubating conditions after succinylcholine and rocuronium.

Conclusion

Use of ephedrine 30 seconds before induction with propofol, fentanyl followed by rocuronium or succinylcholine provides faster good conditions of intubation.