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1.  Improving the outcome of patients with muscle invasive urothelial carcinoma of the bladder with neoadjuvant gemcitabine/cisplatin chemotherapy: A single institution experience 
Introduction:
Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) for muscle invasive urothelial carcinoma of the bladder improves survival. This study was undertaken to determine the rate of neoadjuvant gemcitabine and cisplatin use prior to RC and to assess its effect on the pathologic response rates and cancer-specific survival (CSS) and overall survival (OS).
Methods:
This retrospective chart review examined all patients having a RC between January 1, 2007 and June 30, 2011. We collected patient demographics, pre-treatment clinical stage, type of chemotherapy, post-RC pathologic data and survival data.
Results:
A total of 251 RC were performed of which 160 were for stage cT2–T4 urothelial carcinoma of the bladder. Of the 160 patients, 91 (57%) received neoadjuvant gemcitabine and cisplatin (GC) and 69 (43%) went straight to RC. Patients receiving neoadjuvant GC had a greater chance of achieving a pathologically lower stage compared to the untreated population: pT0 at 21% vs. 3%; non-invasive cancer at 37% vs. 10%; and organ-confined cancer at 60% vs. 33% (p < 0.001). Survival correlated with pathological stage: ≤pT3a patients had a median OS and CSS of 48.8 and 51.2 months compared to an OS and a CSS in ≥pT3b patients of 21.8 and 28.1 months, respectively (p < 0.0001).
Conclusions:
Neoadjuvant chemotherapy for urothelial carcinoma of the bladder is more frequently administered at our institution compared to the published literature. We have found that neoadjuvant chemotherapy increases the rate of down-staging, which is associated with a reduced the risk of death from urothelial carcinoma of the bladder.
doi:10.5489/cuaj.1643
PMCID: PMC4001664  PMID: 24839503
2.  Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study 
The lancet oncology  2012;13(9):10.1016/S1470-2045(12)70285-1.
Summary
Background
The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival—a measure that accounts for elapsed time since treatment initiation—for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies.
Methods
We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival.
Findings
In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0–34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41–47) at 0 months to 51% (46–55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8–15) at 0 months to 33% (18–48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41–47) to 68% (60–75) in the overall population and from 74% (68–79) to 90% (77–96) in the favourable group, 49% (45–53) to 57% (45–67) in the intermediate group, and 11% (8–15) to 73% (43–89) in the poor risk group.
Interpretation
Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.
Funding
The Trust Family Fund for Kidney Cancer Research.
doi:10.1016/S1470-2045(12)70285-1
PMCID: PMC3856362  PMID: 22877847
3.  Neoadjuvant chemotherapy should be administered to fit patients with newly diagnosed, potentially resectable muscle-invasive urothelial cancer of the bladder (MIBC): A 2013 CAGMO Consensus Statement and Call for a Streamlined Referral Process 
Neoadjuvant chemotherapy (NC) improves overall survival in patients with resectable muscle-invasive urothelial cancer of the bladder (MIBC). However uptake of NC in Canada is dis-appointingly low. Following a detailed literature review and in consultation with urologic oncology, the Canadian Association of Genitourinary Medical Oncologists (CAGMO) has developed a consensus statement for the use of NC in MIBC. Our primary goal is to increase the uptake of NC for MIBC in Canada and improve patient outcomes.
doi:10.5489/cuaj.1506
PMCID: PMC3854467  PMID: 24319508
7.  Abiraterone and Increased Survival in Metastatic Prostate Cancer 
The New England journal of medicine  2011;364(21):1995-2005.
BACKGROUND
Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy.
METHODS
We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate.
RESULTS
After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate–prednisone group than in the placebo–prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate–prednisone group than in the placebo–prednisone group.
CONCLUSIONS
The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.)
doi:10.1056/NEJMoa1014618
PMCID: PMC3471149  PMID: 21612468
8.  Correlates of physical activity in a population-based sample of kidney cancer survivors: an application of the theory of planned behavior 
Background
Over half of kidney cancer survivors (KCS) are completely inactive and only a quarter are meeting physical activity (PA) guidelines. This highlights the need to identify and understand the determinants of PA in this understudied population. The purpose of this study is to determine the social cognitive correlates of PA intention and behavior in KCS using the Theory of Planned Behavior (TPB).
Methods
All 1,985 KCS diagnosed between 1996 and 2010 in Alberta, Canada were mailed a self-report survey that consisted of the Godin Leisure Time Exercise Questionnaire and standard TPB items for intention, planning, perceived behavioral control (PBC), affective and instrumental attitudes, and descriptive and injunctive norms. Standard demographic and medical variables were also collected.
Results
Completed surveys were received from 703 of 1,654 (43%) eligible KCS. The TPB was tested using structural equation modelling and demonstrated an adequate-to-good fit to the data [χ² = 256.88, p < .001; TLI = 0.97; CFI = 0.98; RMSEA = 0.06, 90% CI = 0.05-0.06].
There were significant pathways to PA from PBC (ß = 0.18, p = 0.02), planning (ß = 0.22, p < 0.01), and intention (ß = 0.31, p < 0.01); and to planning from intention (ß = 0.81, p < 0.01). In addition, there were significant model pathways to intention from instrumental attitude (ß = 0.28, p = 0.03), descriptive norm (ß = 0.09, p = 0.01), and PBC (ß = 0.52, p < 0.01). Overall, the TPB accounted for 69%, 63%, and 42% of the variance in intention, planning and PA, respectively.
Conclusion
The TPB appears to be a useful model for explaining PA in KCS. All TPB constructs except injunctive norm and affective attitude were useful for explaining intention with PBC emerging as the largest correlate. Developing PA interventions based on the TPB may be effective in promoting PA in KCS and may lead to important improvements in health.
doi:10.1186/1479-5868-9-96
PMCID: PMC3489870  PMID: 22866956
Exercise; Motivation; Social cognitive models; Correlates
10.  A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer 
Introduction:
Docetaxel chemotherapy prolongs survival in metastatic hormone-refractory prostate cancer (mHRPC), but many patients fail to respond to this therapy and there is potential for serious toxicity. Patients differ in their percent prostate-specific antigen (PSA) decline and rate of PSA decline following treatment. We propose that patients who achieve a rapid rate of PSA decline, measured as a shorter PSA half-life (PSAHL), may experience a longer overall survival (OS) than those who achieve a slower rate of PSA decline.
Methods:
A chart review of patients treated with docetaxel for mHRPC in Alberta from January 2000 to May 2006 was performed. At 42 days (after 2 cycles) and 84 days (after 4 cycles) following chemotherapy, PSA response and PSAHL were determined. PSAHL could only be determined in patients with a PSA drop from baseline. Optimal PSAHL values for OS stratification were determined using the log-rank chi-square statistic. Survival analysis was carried out using Kaplan-Meier curves and regression analysis.
Results:
There were 154 patients who fulfilled the inclusion criteria. Using 42-day postdocetaxel data, no associations with OS could be demonstrated. Using 84-day postdocetaxel data, patients stratified by PSAHL demonstrated a significant difference in OS (15 months vs. 25 months) and this relationship remained following multivariate analysis (hazard ratio 0.08 [0.021–0.34]).
Conclusion:
A more rapid rate of PSA decline (PSAHL <70 days) measured after 4 cycles of chemotherapy was associated with a longer OS. This result was independent of other known markers of survival and allowed for a greater survival differentiation than PSA response.
PMCID: PMC2758517  PMID: 19829727
11.  A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment 
Background
We performed a retrospective population-based study to assess the impact of tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients treated for metastatic renal cell carcinoma (mRCC) in Alberta, Canada and to assess the impact of nephrectomy on OS in patients treated with TKIs.
Methods
We identified 134 patients who began taking a TKI between December 2003 and June 2007 for mRCC in Alberta. We compared survival in this group to that in an earlier cohort of 141 patients treated with interferon-α (IFN-α) between May 1995 and March 2003. We used the Kaplan–Meier method to determine OS, and we used a Cox proportional hazards model to determine hazard ratios (HRs) and confidence intervals (CIs). We performed multivariate analysis to assess the impact of neprhectomy on OS.
Results
Of the 134 patients treated with TKIs, 81 received treatment in the first-line setting, whereas 53 received treatment after prior IFN-α therapy. All 141 patients from the IFN-α cohort received treatment in the first-line setting. Patients treated with TKIs had an improved OS compared with the IFN-α cohort (HR 0.61, 95% CI 0.45–0.83, p = 0.001). The median OS was 18 months in the TKI group and 10 months in the IFN-α group. The benefit of TKIs was confined to favourable and intermediate risk groups according to the Memorial Sloan-Kettering Cancer Center prognostic model. Prior nephrectomy was associated with improved OS in the TKI cohort, independent of other prognostic factors.
Conclusion
Tyrosine kinase inhibitors improve OS compared with IFN-α in mRCC. In patients treated with TKIs, prior nephrectomy is associated with improved survival independent of other prognostic variables.
PMCID: PMC2723887  PMID: 19672439
13.  Dr. North's rebuttal 
PMCID: PMC2494890  PMID: 18682769
14.  Malignant spinal cord compression secondary to testicular seminoma at the time of initial presentation and at relapse while on surveillance 
We report cases of 2 pure seminoma patients who developed metastatic spinal cord compressions. One patient was diagnosed at age 33 years with stage 1 seminoma and, after undergoing an orchidectomy, chose to be followed on a surveillance protocol. He was lost to follow-up and presented again 22 months later with back pain, leg weakness and sensory loss when his disease recurred as a spinal cord compression. He was treated with urgent surgical decompression and subsequent standard chemotherapy. More than 2 years posttreatment, he is disease-free with normal neurologic function in his lower extremities. The second patient presented at age 44 years with back pain and rapid loss of leg strength and sensation. Investigations revealed a malignant cord compression with lymphatic and vertebral body metastases. On physical examination, the patient was found to have a 6-cm left testicular mass. He was treated with emergency radiotherapy to the region of his cord compression followed by a left inguinal orchidectomy. Pathology confirmed a pure classic seminoma. Postoperatively, he received standard chemotherapy and eventually regained neurologic function in his legs. Although it is rare for malignant spinal cord compression to occur in seminoma patients—either as the initial presentation of disease or as a site of disease recurrence in stage 1 patients on surveillance—it is crucial to consider seminoma as a possible etiology in young men diagnosed with malignant spinal cord compression because timely contemporary treatments for seminoma will cure most of these patients and offer them excellent functional recovery.
PMCID: PMC2422929  PMID: 18542765

Results 1-14 (14)