Adrian Fairey

Randomized Controlled Trial of Exercise Training in Postmenopausal Breast Cancer Survivors: Cardiopulmonary and Quality of Life Outcomes

PURPOSE To determine the effects of exercise training on cardiopulmonary function and quality of life (QOL) in postmenopausal breast cancer survivors who had completed surgery, radiotherapy, and/or chemotherapy with or without current hormone therapy use. METHODS Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control (n = 28) group. The exercise group trained on cycle ergometers three times per week for 15 weeks at a power output that elicited the ventilatory equivalent for carbon dioxide. The control group did not train. The primary outcomes were changes in peak oxygen consumption and overall QOL from baseline to postintervention. Peak oxygen consumption was assessed by a graded exercise test using gas exchange analysis. Overall QOL was assessed by the Functional Assessment of Cancer Therapy-Breast scale. RESULTS Fifty-two participants completed the trial. The exercise group completed 98.4% of the exercise sessions. Baseline values for peak oxygen consumption (P =.254) and overall QOL (P =.286) did not differ between groups. Peak oxygen consumption increased by 0.24 L/min in the exercise group, whereas it decreased by 0.05 L/min in the control group (mean difference, 0.29 L/min; 95% confidence interval [CI], 0.18 to 0.40; P <.001). Overall QOL increased by 9.1 points in the exercise group compared with 0.3 points in the control group (mean difference, 8.8 points; 95% CI, 3.6 to 14.0; P =.001). Pearson correlations indicated that change in peak oxygen consumption correlated with change in overall QOL (r = 0.45; P <.01). CONCLUSION Exercise training had beneficial effects on cardiopulmonary function and QOL in postmenopausal breast cancer survivors.

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience.

Study Type – Therapy (case series)

Robotic Intracorporeal Orthotopic Ileal Neobladder: Replicating Open Surgical Principles

BACKGROUND Robotic radical cystectomy (RC) for cancer is beginning to gain wider acceptance. Yet, the concomitant urinary diversion is typically performed extracorporeally at most centers, primarily because intracorporeal diversion is perceived as technically complex and arduous. Previous reports on robotic, intracorporeal, orthotopic neobladder may not have fully replicated established open principles of reservoir configuration, leading to concerns about long-term functional outcomes. OBJECTIVE To illustrate step-by-step our technique for robotic, intracorporeal, orthotopic, ileal neobladder, urinary diversion with strict adherence to open surgical tenets. DESIGN, SETTING, AND PARTICIPANTS From July 2010 to May 2012, 24 patients underwent robotic intracorporeal neobladder at a single tertiary cancer center. This report presents data on patients with a minimum of 3-mo follow-up (n=8). SURGICAL PROCEDURE We performed robotic RC, extended lymphadenectomy to the inferior mesenteric artery, and complete intracorporeal diversion. Our surgical technique is demonstrated in the accompanying video. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Baseline demographics, pathology data, 90-d complications, and functional outcomes were assessed and compared with patients undergoing intracorporeal ileal conduit diversion (n=7). RESULTS AND LIMITATIONS Robotic intracorporeal urinary diversion was successfully performed in 15 patients (neobladder: 8 patients, ileal conduit: 7 patients) with a minimum 90-d follow-up. Median age and body mass index were 68 yr and 27 kg/m2, respectively. In the neobladder cohort, median estimated blood loss was 225 ml (range: 100-700 ml), median time to regular diet was 5 d (range: 4-10 d), median hospital stay was 8 d (range: 5-27 d), and 30- and 90-d complications were Clavien grade 1-2 (n=5 and 0), Clavien grade 3-5 (n=2 and 1), respectively. This study is limited by small sample size and short follow-up period. CONCLUSIONS An intracorporeal technique of robot-assisted orthotopic neobladder and ileal conduit is presented, wherein established open principles are diligently preserved. This step-wise approach is demonstrated to help shorten the learning curve of other surgeons contemplating robotic intracorporeal urinary diversion.

Multicenter Assessment of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Does the theory of planned behavior mediate the effects of an oncologist's recommendation to exercise in newly diagnosed breast cancer survivors? Results from a randomized controlled trial.

This randomized trial examined the effects of 2 oncologist-based exercise interventions--recommendation only (RO) and recommendation plus referral (RR)--versus usual care (UC) on social-cognitive constructs from the theory of planned behavior (TPB). The authors also examined whether the TPB mediated the significant effect of the RO intervention on exercise and explained the null effect of the RR intervention. Independent t tests revealed that both interventions had significant effects on TPB constructs; however, only the RO intervention impacted perceived behavioral control (PBC). Path analyses indicated that PBC was the only construct with a direct effect on exercise and that it mediated the effect of the RO intervention on exercise and explained the null effect of the RR intervention.

Associations Among Age, Comorbidity and Clinical Outcomes After Radical Cystectomy: Results From the Alberta Urology Institute Radical Cystectomy Database

PURPOSE We determined the associations among age, comorbidity and clinical outcomes after radical cystectomy. MATERIALS AND METHODS The study was a retrospective cohort analysis of 314 consecutive patients with primary bladder cancer treated with radical cystectomy between January 2000 and December 2006 in Edmonton, Canada. Comorbidity was obtained through a medical record review using the Adult Comorbidity Evaluation-27 instrument. The main clinical outcomes were 90-day mortality, early postoperative complications, and major and minor early postoperative complications. Logistic regression analyses were used to determine predictors of clinical outcomes. RESULTS The 90-day mortality, any early postoperative complications, and major and minor early postoperative complications occurred in 18 (5.7%), 148 (47.1%), 78 (24.8%) and 92 (29.3%) patients, respectively. In univariate and multivariate logistic regression analysis age was not associated with 90-day mortality or early postoperative complications. In contrast, compared to patients with no or mild comorbidity, multivariate logistic regression analysis adjusted for age and surgeon procedure volume showed that severe comorbidity was associated with an increased risk of 90-day mortality (OR 6.4, p = 0.03). In addition, compared to patients with no or mild comorbidity, multivariate logistic regression analysis adjusted for age, sex, surgeon procedure volume, type of urinary tract reconstruction and American Joint Committee on Cancer stage showed that moderate and severe comorbidity were associated with any early postoperative complications (moderate OR 5.2, p <0.001; severe OR 7.0, p <0.001), major early postoperative complications (moderate OR 11.4, p <0.001; severe OR 15.2, p <0.001) and minor early postoperative complications (moderate OR 2.1, p = 0.019; severe OR 2.2, p = 0.038). CONCLUSIONS Increasing comorbidity was independently associated with an increased risk of 90-day mortality and early postoperative complications after radical cystectomy.

Conditional Survival After Radical Cystectomy for Bladder Cancer: Evidence for a Patient Changing Risk Profile over Time

BACKGROUND Standard survival statistics do not take into consideration the changes in the weight of individual variables at subsequent times after the diagnosis and initial treatment of bladder cancer. OBJECTIVE To assess the changes in 5-yr conditional survival (CS) rates after radical cystectomy for bladder cancer and to determine how well-established prognostic factors evolve over time. DESIGN, SETTING, AND PARTICIPANTS We analyzed data from 8141 patients treated with radical cystectomy at 15 international academic centers between 1979 and 2012. INTERVENTIONS Radical cystectomy and pelvic lymph node dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Conditional cancer-specific survival (CSS) and overall survival (OS) estimates were calculated using the Kaplan-Meier method. The multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality after stratification by clinical characteristics (age, perioperative chemotherapy status) and pathologic characteristics (pT stage, grade, lymphovascular invasion, pN stage, number of nodes removed, margin status). The median follow-up was 32 mo. RESULTS AND LIMITATIONS The 5-yr CSS and OS rates were 67.7% and 57.5%, respectively. Given a 1-, 2-, 3-, 5- and 10-yr survivorship, the 5-yr conditional OS rates improved by +5.6 (60.7%), +8.4 (65.8%), +7.6 (70.8%), +3.0 (72.9%), and +1.9% (74.3%), respectively. The 5-yr conditional CSS rates improved by +5.6 (71.5%), +9.8 (78.5%), +7.9 (84.7%), +7.2 (90.8%), and 5.6% (95.9%), respectively. The 5- and 10-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. Findings were confirmed on multivariable analyses. The main limitation was the retrospective design. CONCLUSIONS CS analysis demonstrates that the patient risk profile changes over time. The risk of mortality decreases with increasing survivorship. The CS rates improve mainly in the case of advanced stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS.

Associations Between Comorbidity, and Overall Survival and Bladder Cancer Specific Survival After Radical Cystectomy: Results From the Alberta Urology Institute Radical Cystectomy Database

PURPOSE We determined the associations between comorbidity, and overall survival and bladder cancer specific survival after radical cystectomy. MATERIALS AND METHODS The Alberta Urology Institute Radical Cystectomy database is an ongoing multi-institutional computerized database containing data on all adult patients with a diagnosis of primary bladder cancer treated with radical cystectomy in Edmonton, Canada from April 1994 forward. The current study is an analysis of consecutive database patients treated between April 1994 and September 2007. Comorbidity information was obtained through a medical record review using the Adult Comorbidity Evaluation 27 instrument. The outcome measures were overall survival and bladder cancer specific survival. Cox proportional regression analysis was used to determine the associations between comorbidity, and overall survival and bladder cancer specific survival. RESULTS Of the database patients 160 (34%), 225 (48%) and 83 (18%) had no/mild comorbidity, moderate comorbidity and severe comorbidity, respectively. Compared to patients with no or mild comorbidity, multivariate Cox proportional regression analyses that included age, adjuvant chemotherapy, surgeon procedure volume, pathological T stage, pathological lymph node status, total number of lymph nodes removed, surgical margin status and lymphovascular invasion showed that increased comorbidity was independently associated with overall survival (moderate HR 1.59, 95% CI 1.16-2.18, p = 0.004; severe HR 1.83, 95% CI 1.22-2.72, p = 0.003) and bladder cancer specific survival (moderate HR 1.50, 95% CI 1.04-2.15, p = 0.028; severe HR 1.65, 95% CI 1.04-2.62, p = 0.034). CONCLUSIONS Increased comorbidity was independently associated with an increased risk of overall mortality and bladder cancer specific mortality after radical cystectomy.

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.

Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: A retrospective analysis from the University of Southern California☆

OBJECTIVES We evaluated pathologic and survival outcomes of GC (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M-VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS A retrospective analysis of prospectively collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58) before radical cystectomy and superextended pelvic lymph node dissection for clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and multivariable Cox regression analysis were used to analyze OM. The cumulative incidence method and Fine and Grays competing risk regression analysis were used to analyze recurrence. RESULTS The median follow-up duration was 2.1 years for the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no statistically significant differences between the GC and M-VAC groups with regard to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups. Multivariable analysis showed that there was no independent association between type of NAC and OM (P = 0.721) or recurrence (P = 0.065). CONCLUSIONS Pathologic and survival outcomes did not differ in patients who received GC and M-VAC NAC. These data support the use of the GC regimen in the neoadjuvant setting.