Peter Venner

GENITOURINARY SMALL CELL CARCINOMA: DETERMINATION OF CLINICAL AND THERAPEUTIC FACTORS ASSOCIATED WITH SURVIVAL

PURPOSEnWe assessed the prognostic impact of genitourinary small cell carcinoma tumor and patient characteristics, and therapy.nnnMATERIALS AND METHODSnWe retrospectively reviewed the records of 180 patients with genitourinary small cell carcinoma in which patient and tumor characteristics, therapy, followup duration and survival status had been documented. Patient age, sex, primary site, histological features, tumor size, stage, locoregional therapy, systemic chemotherapy and hormonal manipulations were analyzed for association with survival.nnnRESULTSnThere were 106 cases of bladder, 60 prostatic, 8 renal and 6 ureteral small cell carcinoma. Median survival was 10.5 months overall, and 7 and 13 months for prostatic and bladder small cell carcinoma, respectively (p <0.0001 log rank analysis). In all cases metastatic disease at presentation (p <0.008, risk ratio 1.9) predicted poor survival on multivariate analysis. Radical surgery (p <0.0001, risk ratio 0.34) and cisplatin chemotherapy (p <0.0001, risk ratio 0.20) were the only factors that predicted improved survival on multivariate analysis. For prostatic small cell carcinoma primary surgical therapy (p <0.012, risk ratio 0.46) was the only parameter that predicted survival on univariate analysis. For bladder small cell carcinoma only cisplatin chemotherapy (p <0.0001, risk ratio 0.15) predicted survival on multivariate analysis.nnnCONCLUSIONSnGenitourinary small cell carcinoma has a poor prognosis, which is worse in prostatic than bladder disease. Patient and tumor characteristics were not determinants of survival when prostatic and bladder small cell carcinoma were analyzed individually. For prostatic disease only primary surgical therapy was associated with prolonged survival, while for bladder disease cisplatin chemotherapy was associated with a favorable prognosis. We recommend considering primary surgical therapy for prostatic and cisplatin based chemotherapy for bladder small cell carcinoma.

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

PURPOSEnWe determined the associations between comorbidity, and overall survival and bladder cancer specific survival after radical cystectomy.nnnMATERIALS AND METHODSnThe 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.nnnRESULTSnOf 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).nnnCONCLUSIONSnIncreased comorbidity was independently associated with an increased risk of overall mortality and bladder cancer specific mortality after radical cystectomy.

Referral and treatment rates of neoadjuvant chemotherapy in muscle-invasive bladder cancer before and after publication of a clinical practice guideline.

INTRODUCTIONnThe objective of this study was to compare referral and treatment rates of neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer before and after publication of a clinical practice guideline.nnnMETHODSnThis was a retrospective comparative cohort study of 236 patients diagnosed with clinical stage >/= T2 bladder cancer in Alberta, Canada. Patients were divided into 2 groups based on the time of diagnosis relative to the publication of the Alberta Genitourinary Oncology Group Clinical Practice Guideline on Bladder Cancer (CPG), which recommends cisplatin-based neoadjuvant chemotherapy for muscle-invasive disease. The pre-CPG group included patients (n = 129) diagnosed prior to publication of the CPG (November 1, 2002 to October 31, 2004, inclusively). The post-CPG group included patients (n = 107) diagnosed after publication of the CPG (November 1, 2005 to October 31, 2007). There was an accrual blackout period of 6 months before and after the CPG release date. The primary analysis compared the two groups with respect to neoadjuvant chemotherapy referral rates, treatment-offered rates and treatment-administered rates.nnnRESULTSnReferral to medical oncology regarding neoadjuvant chemotherapy occurred in 2.3% and 23.4% of patients in the pre- and post-CPG groups, respectively (p < 0.01). Neoadjuvant chemotherapy was offered to 0.8% and 18.7% of patients in the pre- and post-CPG groups, respectively (p < 0.01). Neoadjuvant chemotherapy was administered to 0.8% and 14.0% of patients in the pre- and post-CPG groups, respectively (p < 0.01).nnnINTERPRETATIONnNeoadjuvant referral and treatment rates increased after publication of the CPG. However, overall referral and treatment rates remained low, which warrants additional exploration.

A Phase II Trial of Triamcinolone Hexacetanide for Symptomatic Recurrent Malignant Ascites

Ascites is a common complication of advanced cancer and frequently requires paracentesis to reduce symptoms of pain, anorexia, and dyspnea. For many patients repeat paracenteses are required at short intervals. We prospectively studied 15 patients with recurrent ascites of malignancy to determine if intraperitoneal triamcinolone hexacetonide, a slowly metabolized corticosteroid, produced objective and symptomatic responses. After biochemical, radiological, and symptom assessment and the establishment of the interval between paracenteses, patients underwent large-volume paracentesis followed by intraperitoneal triamcinolone hexacetonide 10 mg/kg. Patients were followed after treatment for assessment of symptoms and physical signs of ascites. Repeat paracentesis was performed when symptomatic ascites recurred. Symptomatic ascites recurred in 13 of 15 patients, but the interval between paracenteses was extended from 9.5 +/- 1.6 days to 17.5 days (P = 0.0086). Symptom questionnaire scores assessing well-being, nausea, abdominal pain, dyspnea, appetite, appearance, and change in abdominal size on a scale from 0 to 6 averaged 3.2 +/- 0.3 at entry and 2.5 +/- 0.2 at the 2-week assessment (P = 0.026). Self-assessed symptoms, feeling of well-being, abdominal distention, and physical appearance improved significantly. The mean serum cortisol decreased from baseline, suggesting that some systemic corticosteroid absorption occurred. Thirteen of 15 patients have died, with a median survival of 42 days. Potential adverse effects included 1 episode each of transient abdominal pain, bacterial peritonitis, and localized herpes zoster infection. In patients with ascites of malignancy, intraperitoneal triamcinolone hexacetonide appears to postpone the requirement for repeat paracentesis and improve symptoms of malignant ascites.

The Lack of Long-Term Effect of Cisplatin Based Combination Chemotherapy on Serum Cholesterol for Treatment of Testicular Cancer

PURPOSEnCisplatin based combination therapy is curative in most patients with advanced testicular cancer. Previous reports have suggested that hypercholesterolemia is a common complication in this patient group. We performed a cross-sectional study to assess further the relationship of cisplatin based chemotherapy and serum cholesterol in long-term survivors of testicular cancer.nnnMATERIALS AND METHODSnFasting lipid profiles were obtained from 106 men previously treated for testicular cancer, of whom 34 had received cisplatin based combination chemotherapy and 72 were chemotherapy naive.nnnRESULTSnMean total cholesterol in the chemotherapy and nonchemotherapy groups was 5.50 +/- 0.20 and 5.36 +/- 0.13 mmol./l., respectively (p = 0.55). Mean high density lipoprotein cholesterol in the chemotherapy and nonchemotherapy groups was 1.09 +/- 0.04 and 1.09 +/- 0.03 mmol./l., (p = 0.94), while mean low density lipoprotein cholesterol was 3.49 +/- 0.17 and 3.40 +/- 0.11 mmol./l. (p = 0.67) respectively. The mean total-to-high density lipoprotein cholesterol ratio was 5.26 +/- 0.27 in the chemotherapy group and 5.12 +/- 0.16 in the nonchemotherapy group (p = 0.67). Body mass index was not significantly different in the 2 groups.nnnCONCLUSIONSnAdministering cisplatin based chemotherapy was unrelated to lipid profiles in long-term survivors of testicular cancer. Chemotherapy treated and chemotherapy naive patients had mean cholesterol levels in the borderline elevated range and body mass index in the overweight range. These potentially reversible cardiovascular risk factors have considerable importance in the overall testicular cancer population.

Seminoma with Isolated Central Nervous System Relapse, and Salvage with Craniospinal Irradiation

We report a case of a patient with isolated central nervous system relapse of classical seminoma, refractory to intrathecal and systemic chemotherapy, but successfully salvaged with craniospinal axis irradiation. A 44-year-old man with bulky Stage II classic seminoma obtained complete remission with four cycles of cisplatin etoposide combination chemotherapy, but relapsed with lumbar vertebral metastases with epidural spinal cord compression 5 months after completion of primary treatment. He underwent laminectomy, local radiotherapy, and salvage chemotherapy. Two months later he developed cranial nerve palsies, and magnetic resonance imaging confirmed leptomeningeal disease. After brain radiotherapy, systemic and intrathecal chemotherapies were begun but tumor recurred around the cauda equina, producing paraparesis. The patient received salvage craniospinal irradiation, with resolution of paraparesis and cranial nerve palsies. Thirty months after completion of craniospinal radiotherapy, he remains in complete remission. We suggest consideration of craniospinal axis irradiation as salvage therapy in patients with isolated central nervous system relapse of seminoma.

Furthering the prostate cancer screening debate (prostate cancer specific mortality and associated risks)

Screening for prostate cancer remains a contentious issue. As with other cancer screening programs, a key feature of the debate is verification of cancer-specific mortality reductions. Unfortunately the present evidence, two systematic reviews and six randomized controlled trials, have reported conflicting results. Furthermore, half of the studies are poor quality and the evidence is clouded by key weaknesses, including poor adherence to screening in the intervention arm or high rates of screening in the control arm. In high quality studies of prostate cancer screening (particularly prostate-specific antigen), in which actual compliance was anticipated in the study design, there is good evidence that prostate cancer mortality is reduced. The numbers needed to screen are at least as good as those of mammography for breast cancer and fecal occult blood testing for colorectal cancer. However, the risks associated with prostate cancer screening are considerable and must be weighed against the advantage of reduced cancer-specific mortality. Adverse events include 70% rate of false positives, important risks associated with prostate biopsy, and the serious consequences of prostate cancer treatment. The best evidence demonstrates prostate cancer screening will reduce prostate cancer mortality. It is time for the debate to move beyond this issue, and begin a well-informed discussion on the remaining complex issues associated with prostate cancer screening and appropriate management.

Predictive factors for outcome in treatment of metastatic nonseminomatous germ cell tumors

In recent years less intensive chemotherapy programs for patients with metastatic nonseminomatous germ cell tumors with high likelihood of cure have been proposed, and the use of innovative more intensive treatments for patients with less favorable prognosis is being explored. The development of validated prognostic classifications has thus become important. In 77 patients with metastatic nonseminomatous germ cell tumors treated with chemotherapy, the ability of various prognostic factors to predict outcome of treatment was assessed. The multifactorial prognostic classification (Indiana classification) and a mathematical predictive formula correctly allocated patients to low- or high-risk groups in 84.4 percent and 87.0 percent of cases. The multifactorial classification system (M.D. Anderson system) correctly allocated patients in 61 percent of cases. The presence of serum beta HCG levels over 1,000 mg/mL, a pure choriocarcinoma histology and possibly an extragonadal primary origin of tumor were found to predict an adverse outcome in a small number of patients. It is concluded that use of the Indiana classification or mathematical predictive formula is an accurate means of allocating patients with metastatic germ cell tumors to high- or low-risk groups and that allocation of patients with pure choriocarcinoma histology, very high beta HCG levels, or extragonadal primary origin of tumor to the poor prognosis category will improve the accuracy of prediction in a few cases.

First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The Canadian experience

INTRODUCTIONnClinical trial data has shown pazopanib to be non-inferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting.nnnMETHODSnData were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method.nnnRESULTSnWe identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130; aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease; patients treated with pazopanib had a higher incidence of hepatotoxicity.nnnCONCLUSIONSnIn Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of individualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.

Determinants of Accrual to Prostate Cancer Clinical Trials

Purpose : Progress in the management of prostate cancer depends on the timely completion of clinical trials that address important relevant treatment questions. This study examines the accrual process for prostate cancer clinical trials to elicit specific reasons why patients are not being accrued at higher rates at two Canadian cancer centers. Methods : A chart review was conducted on all prostate cancer patients who were referred for a treatment consultation at the centers during two, one-month periods. Patients were prospectively tracked for trial eligibility, whether they were approached for trial participation, and if so whether they accepted or declined. Telephone interviews were conducted in one of the centers on those patients who were approached to determine the reasons for their decisions regarding trial participation. Results : Of 359 patients seen for a treatment decision, 48.2% were eligible for at least one trial, 67.6% of eligible patients were approached to participate in a trial, and 46.2...