Study Type - Prognosis (inception cohort) Level of Evidence 1b OBJECTIVE To examine the effect of short-course androgen-suppression therapy (AST) before brachytherapy on all-cause mortality (ACM) rates, stratified by the presence or absence of a history of myocardial infarction (MI) or stroke. AST is used to reduce prostate size to enable men with favourable-risk prostate cancer to undergo brachytherapy, but no disease-specific benefit has been reported for this practice, and AST use has been associated with an increased risk of ACM in some men with pre-existing cardiovascular disease. PATIENTS AND METHODS The study comprised 12 792 men with favourable-risk disease, i.e. a prostate-specific antigen (PSA) level of <20 ng/mL, Gleason score </=7 and clinical category </=T2c, treated between 1991 and 2007 at community-based medical centres with brachytherapy +/- neoadjuvant AST. Multivariable Cox regression analysis was used to assess whether there were significant associations between AST use in men with a history of MI or stroke and the risk of ACM, adjusting for age, treatment year, and known prognostic factors of prostate cancer. RESULTS After a median (interquartile range) follow-up of 3.8 (2.0-5.9) years there were 1557 deaths. The risk of ACM was lower in men with no history of MI or stroke than in those with this history, whether AST was used (adjusted hazard ratio 0.79, 95% confidence interval 0.67-0.92; P= 0.003) or not (0.74, 0.65-0.85; P < 0.001). However, men with a history of MI or stroke treated with AST had a greater risk of ACM than those not treated with AST (1.2, 1.05-1.38; P= 0.008). CONCLUSION The use of short-course AST in men with a history of MI or stroke is associated with a greater risk of ACM in men with favourable-risk prostate cancer.

Abstract Background: Adequate colonic imaging is generally an invasive procedure with attendant risks, particularly perforation. Endoscopy, barium enema and CT colonography are the main techniques for investigating patients with symptoms of, or screening for, colorectal cancer. The potential complications of these investigations have to be weighed against the benefits. This paper reviews the literature on the incidence, presentation and management of iatrogenic colonic perforation at colonic imaging. Methods: A literature review of relevant studies was undertaken using Pub Med, Cochrane library, and personal archives of references. Manual cross referencing was performed and relevant references from selected articles were reviewed. Studies reporting complications of endoscopy, barium enema and CT colonography were included in this review. Results: Twenty four studies were identified comprising of 640, 433 colonoscopies with iatrogenic perforation recorded in 585 patients (0.06%). The reported perforation rate with DCBE was between 0.02-0.24%. Serious complications with CTC were infrequent, though nine perforations were reported in a case series of 24,365 patients (0.036%) undergoing CTC. Conclusion: Perforation remains an infrequent and almost certainly under-reported, complication of all colonic imaging modalities. Risk awareness, early diagnosis and active management of iatrogenic perforation minimizes an adverse outcome.

PURPOSE: Patients with low rectal cancer have worse outcomes compared to those with upper rectal cancer. Reports suggest that low anterior resection may be oncologically superior to abdominoperineal excision, although no good evidence exists to support this. We looked at a recent series of patients with low rectal cancer to explore some of the issues. METHODS: We analyzed 153 patients from the MERCURY study with low rectal cancer (<or=6 cm from the anal verge). The median tumor height, percentage undergoing neoadjuvant therapy, involved margin rates, and degree of local invasion were compared for abdominoperineal excision vs low anterior resection. RESULTS: The mean tumor height from the anal verge was 2.9 cm for the patients with abdominoperineal excision vs 4.6 cm in the patients with low anterior resection. The involved margin rate was 20% overall, but was 31.9% for abdominoperineal excision vs 12% for low anterior resection. More patients who had abdominoperineal excision had neoadjuvant therapy (64% vs 41%) and a higher proportion had more locally advanced (T4) tumors. CONCLUSION: Patients undergoing abdominoperineal excision have higher involved margin rates; however, they had lower and more locally extensive tumors despite a greater proportion undergoing neoadjuvant therapy. Patients with low rectal cancer pose difficulties with regard to optimal management. Targeted strategies are needed to improve outcome in this complex and common cancer.

Cancer of the low rectum provides a challenge for both preoperative staging and optimum operative management. Current outcomes for patients with low rectal cancer are poor, particularly for those treated by abdominoperineal excision. It has been suggested that this poor outcome is due to an inherent oncological inferiority of the traditional abdominoperineal excision procedure, which might be explained by the unique anatomical features of the low rectum and the lack of clearly defined anatomical excision planes. In this Personal View, we discuss the anatomical and surgical planes available for the management of low rectal cancer, and describe the two-plane approach to low rectal cancer using the mesorectal plane and the extralevator plane.

PURPOSE: This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). PATIENTS AND METHODS: A multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival. RESULTS: Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P <.001), absence of lymph node metastasis (P <.001), completeness of cytoreduction scores of CC-0 or CC-1 (P <.001), and HIPEC (P =.002). CONCLUSION: The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.

PURPOSE: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. METHODS: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whether PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. RESULTS: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p =.002) to present with high-grade PCa but were not treated less aggressively (p =.33) and did not have an increased risk of PCSM (p =.58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p =.035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p =.001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p =.01) compared to favorable-risk PCa. CONCLUSION: Aggressive management of pDM is warranted in men with high-risk PCa.

PURPOSE: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy. METHODS AND MATERIALS: The study cohort comprised 1,978 men of median age 71 (interquartile range, 66-75) years with intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20 ng/mL or less, tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether prevalent cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category was associated with the risk of PCSM. RESULTS: After a median follow-up of 3.2 (interquartile range, 1.7-5.4) years, the presence of CVD was significantly associated with a decreased risk of PCSM (adjusted hazard ratio, 0.20; 95% CI 0.04-0.99; p = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (adjusted hazard ratio 1.14; 95% CI 1.02-1.27; p = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (p = 0.03) in men with PSA levels above as compared with the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (p = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL). CONCLUSIONS: In elderly men with intermediate-risk prostate cancer, CVD status is a negative predictor of PCSM and affects the prognostic capacity of pretreatment PSA level. These observations support the potential utility of prerandomization stratification by comorbidity to more accurately assess prognostic factors and treatment effects within this population.

CONTEXT: Hormonal therapy (HT) when added to radiation therapy (RT) for treating unfavorable-risk prostate cancer leads to an increase in survival except possibly in men with moderate to severe comorbidity. However, it is unknown which comorbid conditions eliminate this survival benefit. OBJECTIVE: To assess whether neoadjuvant HT use affects the risk of all-cause mortality in men with prostate cancer and coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI), CAD risk factors, or no comorbidity. DESIGN, SETTING, AND PATIENTS: A total of 5077 men (median age, 69.5 years) with localized or locally advanced prostate cancer were consecutively treated with or without a median of 4 months of neoadjuvant HT followed by RT at a suburban cancer center between 1997 and 2006 and were followed up until July 1, 2008. Cox regression multivariable analyses were performed assessing whether neoadjuvant HT use affected the risk of all-cause mortality, adjusting for age, year and type of RT, treatment propensity score, and known prostate cancer prognostic factors in each comorbidity group. MAIN OUTCOME MEASURE: Risk of all-cause mortality. RESULTS: Neoadjuvant HT use was not associated with an increased risk of all-cause mortality in men with no comorbidity (9.6% vs 6.7%, adjusted hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.72-1.32; P =.86) or a single CAD risk factor (10.7% vs 7.0%, adjusted HR, 1.04; 95% CI, 0.75-1.43; P =.82) after median follow-ups of 5.0 and 4.4 years, respectively. However, for men with CAD-induced CHF or MI, after a median follow-up of 5.1 years, neoadjuvant HT use was significantly associated with an increased risk of all-cause mortality (26.3% vs 11.2%, adjusted HR, 1.96; 95% CI, 1.04-3.71; P =.04). CONCLUSION: Neoadjuvant HT use is significantly associated with an increased risk of all-cause mortality among men with a history of CAD-induced CHF or MI but not among men with no comorbidity or a single CAD risk factor.