Sam Egger

Quality of life three years after diagnosis of localised prostate cancer: population based cohort study

Objective To quantify the risk and severity of negative effects of treatment for localised prostate cancer on long term quality of life. Design Population based, prospective cohort study with follow-up over three years. Setting New South Wales, Australia. Participants Men with localised prostate cancer were eligible if aged less than 70 years, diagnosed between October 2000 and October 2002, and notified to the New South Wales central cancer registry. Controls were randomly selected from the New South Wales electoral roll and matched to cases by age and postcode. Main outcome measures General health specific and disease specific function up to three years after diagnosis, according to the 12 item short form health survey and the University of California, Los Angeles prostate cancer index. Results 1642 (64%) cases and 495 (63%) eligible and contacted controls took part in the study. After adjustment for confounders, all active treatment groups had low odds of having better sexual function than controls, in particular men on androgen deprivation therapy (adjusted odds ratio (OR) 0.02, 95% CI 0.01 to 0.07). Men treated surgically reported the worst urinary function (adjusted OR 0.17, 95% CI 0.13 to 0.22). Bowel function was poorest in cases who had external beam radiotherapy (adjusted OR 0.44, 95% CI 0.30 to 0.64). General physical and mental health scores were similar across treatment groups, but poorest in men who had androgen deprivation therapy. Conclusions The various treatments for localised prostate cancer each have persistent effects on quality of life. Sexual dysfunction three years after diagnosis was common in all treatment groups, whereas poor urinary function was less common. Bowel function was most compromised in those who had external beam radiotherapy. Men with prostate cancer and the clinicians who treat them should be aware of the effects of treatment on quality of life, and weigh them up against the patient’s age and the risk of progression of prostate cancer if untreated to make informed decisions about treatment.

Superior Quality of Life and Improved Surgical Margins Are Achievable with Robotic Radical Prostatectomy After a Long Learning Curve: A Prospective Single-surgeon Study of 1552 Consecutive Cases

BACKGROUND Comparative studies suggest functional and perioperative superiority of robot-assisted radical prostatectomy (RARP) over open radical prostatectomy (ORP). OBJECTIVE To determine whether high-volume experienced open surgeons can improve their functional and oncologic outcomes with RARP and, if so, how many cases are required to surpass ORP outcomes and reach the learning curve plateau. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study compared two surgical techniques: 1552 consecutive men underwent RARP (866) or ORP (686) at a single Australian hospital from 2006 to 2012, by one surgeon with 3000 prior ORPs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Demographic and clinicopathologic data were collected prospectively. The Expanded Prostate Cancer Index Composite quality of life (QoL) questionnaire was administered at baseline, 1.5, 3, 6, 12, and 24 mo. Multivariate linear and logistic regression modelled the difference in QoL domains and positive surgical margin (PSM) odds ratio (OR), respectively, against case number. RESULTS AND LIMITATIONS A total of 1511 men were included in the PSM and 609 in the QoL analysis. RARP sexual function scores surpassed ORP scores after 99 RARPs and increased to a mean difference at 861st case of 11.0 points (95% confidence interval [CI], 5.9-16.1), plateauing around 600-700 RARPs. Early urinary incontinence scores for RARP surpassed ORP after 182 RARPs and increased to a mean difference of 8.4 points (95% CI, 2.1-14.7), plateauing around 700-800 RARPs. The odds of a pT2 PSM were initially higher for RARP but became lower after 108 RARPs and were 55% lower (OR: 0.45; 95% CI, 0.22-0.92) by the 866th RARP. The odds of a pT3/4 PSM were initially higher for RARP but decreased, plateauing around 200-300 RARPs with an OR of 1.15 (0.68-1.95) at the 866th RARP. Limitations include single-surgeon data and residual confounding. CONCLUSIONS RARP had a long learning curve with inferior outcomes initially, and then showed progressively superior sexual, early urinary, and pT2 PSM outcomes and similar pT3 PSM and late urinary outcomes. Learning RARP was worthwhile for this high-volume surgeon, but the learning curve may not be justifiable for late-career/low-volume surgeons; further studies are needed.

Injectable and oral contraceptive use and cancers of the breast, cervix, ovary, and endometrium in black South African women: case-control study.

A case-control study conducted in South Africa provides new estimates of the risk of specific cancers of the female reproductive system associated with use of injectable and oral contraceptives.

InterSCOPE Study: Associations Between Esophageal Squamous Cell Carcinoma and Human Papillomavirus Serological Markers

BACKGROUND The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case-control studies conducted in regions with differing background risks of esophageal cancer. METHODS We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case-control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided. RESULTS We found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P = .023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P < .001) but not for other tested HPV types. There were no statistically significant associations between esophageal squamous cell carcinoma and antibodies to E7 for any of the tested HPV types. Simultaneous seropositivity for HPV16 E6 and E7 was rare (four case subjects, two control subjects; OR = 5.57, 95% CI = 0.90 to 34.35; P = .064). We also found statistically significant associations between esophageal squamous cell carcinoma and capsid antibodies for the high-risk mucosal type HPV33 L1 (OR = 1.30, 95% CI = 1.00 to 1.69; P = .047) and the low-risk mucosal types HPV6 (OR = 1.22, 95% CI = 1.05 to 1.42; P = .010) and HPV11 (OR = 1.30, 95% CI = 1.09 to 1.56, P = .0036). CONCLUSIONS We found limited serological evidence of an association between esophageal squamous cell carcinoma and HPV in the populations studied. Although HPV does not appear to be an important risk factor for esophageal squamous cell carcinoma, we cannot exclude the possibility that certain HPV types may be involved in a small subset of cancers.

Smoking cessation after cancer.

Freddy Sitas, Cancer Council New South Wales, Wooloomooloo; University of Sydney, Camperdown; and University of New South Wales, Kensington, New South Wales, Australia Marianne F. Weber, Cancer Council New South Wales, Wooloomooloo; and University of Sydney, Camperdown, New South Wales, Australia Sam Egger, Sarsha Yap, and May Chiew, Cancer Council New South Wales, Wooloomooloo, New South Wales, Australia Dianne O’Connell, Cancer Council New South Wales, Wooloomooloo; University of Sydney, Camperdown; University of New South Wales, Kensington; and University of Newcastle, Callaghan, New South Wales, Australia

Differences among the coloured, white, black, and other South African populations in smoking-attributed mortality at ages 35-74 years: a case-control study of 481,640 deaths.

BACKGROUND The full eventual effects of current smoking patterns cannot yet be seen in Africa. In South Africa, however, men and women in the coloured (mixed black and white ancestry) population have smoked for many decades. We assess mortality from smoking in the coloured, white, and black (African) population groups. METHODS In this case-control study, 481,640 South African notifications of death at ages 35-74 years between 1999 and 2007 yielded information about age, sex, population group, education, smoking 5 years ago (yes or no), and underlying disease. Cases were deaths from diseases expected to be affected by smoking; controls were deaths from selected other diseases, excluding only HIV, cirrhosis, unknown causes, external causes, and mental disorders. Disease-specific case-control comparisons yielded smoking-associated relative risks (RRs; diluted by combining some ex-smokers with the never-smokers). These RRs, when combined with national mortality rates, yielded smoking-attributed mortality rates. Summation yielded RRs and smoking-attributed numbers for overall mortality. FINDINGS In the coloured population, smoking prevalence was high in both sexes and smokers had about 50% higher overall mortality than did otherwise similar non-smokers or ex-smokers (men, RR 1·55, 95% CI 1·43-1·67; women, 1·49, 1·38-1·60). RRs were similar in the white population (men, 1·37, 1·29-1·46; women, 1·51, 1·40-1·62), but lower among Africans (men, 1·17, 1·15-1·19; women, 1·16, 1·13-1·20). If these associations are largely causal, smoking-attributed proportions for overall male deaths at ages 35-74 years were 27% (5608/20,767) in the coloured, 14% (3913/28,951) in the white, and 8% (20,398/264,011) in the African population. For female deaths, these proportions were 17% (2728/15,593) in the coloured, 12% (2084/17,899) in the white, and 2% (4038/205,623) in the African population. Because national mortality rates were also substantially higher in the coloured than in the white population, the hazards from smoking in the coloured population were more than double those in the white population. INTERPRETATION The highest smoking-attributed mortality rates were in the coloured population and the lowest were in Africans. The substantial hazards already seen among coloured South Africans suggest growing hazards in all populations in Africa where young adults now smoke. FUNDING South African Medical Research Council, UK Medical Research Council, Cancer Research UK, British Heart Foundation, New South Wales Cancer Council.

Marketing cigarettes when all else is unavailable: evidence of discounting in price-sensitive neighbourhoods

Objective Since price is both a key determinant of smoking and one of the few remaining marketing strategies available in countries without point-of-sale tobacco display, this study examines cigarette price variations in the Australian market and assesses whether those variations are consistent with price being used to increase or maintain smoking among price-sensitive groups. Method An audit of 1739 tobacco retailers was used to collect variations in the price of the best-selling Australian cigarette brand, as well as record retailer compliance with tobacco retailing legislation. We examined variation in pricing across outlet type, demographic variations (socioeconomic level, % in the area under 18 and % born in Australia), remoteness and retailer compliance with tobacco retailing legislation. Results Multipacks were offered by 27.8% of retailers, with the average pack price in a twin pack

Sun exposure may increase risk of prostate cancer in the high UV environment of New South Wales, Australia: A case–control study

1.32 (or 7.3%) cheaper than a single pack. Prices were significantly lower in some outlet types, in lower socioeconomic postcodes and in those with a higher percentage of people under 18. In contrast with other consumer goods, prices were lower (although not significantly so) outside major cities. Conclusions The provision of substantial multi-pack discounts and lower prices in postcodes with a higher proportion of price-sensitive smokers (young people and those from lower socioeconomic groups) is consistent with targeted discounts being used as a tobacco marketing strategy. The results support policy interventions to counter selective discounts and to require disclosure of trade-based discounts.

Mucosal Alpha-Papillomaviruses are not associated with Esophageal Squamous Cell Carcinomas: Lack of Mechanistic Evidence from South Africa, China and Iran and from a World-Wide Meta-Analysis.

Ultraviolet (UV) radiation in sunlight may influence risk of prostate cancer. In New South Wales (NSW), Australia, we examined the relationship between sun exposure at 30 and 50 years of age and risk of prostate cancer in a case–control study combining the NSW prostate cancer care and outcome study (cases) and the NSW non‐Hodgkins lymphoma study (controls). Prostate cancer risk increased with increasing estimated sun exposure (adjusted OR for highest vs. lowest quartiles of average weekly sun exposure in the warmer months 2.07 95% CI: 1.36–3.15) and this increase was most evident with weekend sun exposure (adjusted OR = 5.55, 95% CI: 2.94–10.48). High sun sensitivity was also positively associated with risk for prostate cancer (adjusted OR = 1.63, 95% CI: 1.09–2.44). The apparent effects of weekly sun exposure did not vary by disease aggressiveness. Our results suggest that increasing sun exposure in mid‐adult years increases prostate cancer risk in a high ambient solar UV environment. Given that previous studies, conducted mainly in low solar UV environments, have generally found evidence of a negative association, our findings suggest there may be a U‐shaped relationship between solar UV exposure and prostate cancer. Further studies are needed to test the hypothesis that high solar UV exposure is a risk factor for prostate cancer and to explore possible mechanisms for such an association.

Adult body size, sexual history and adolescent sexual development, may predict risk of developing prostate cancer: Results from the New South Wales Lifestyle and Evaluation of Risk Study (CLEAR)

Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol‐ and formalin‐fixed paraffin‐embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high‐incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha‐papillomaviruses by two sensitive, broad‐spectrum genotyping methods, and for the markers of HPV‐transformed phenotype: (i) HPV16/18 viral loads by quantitative real‐time PCR, (ii) type‐specific viral mRNA by E6*I/E6 full‐length RT‐PCR assays and (iii) expression of cellular protein p16INK4a. Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16INK4a negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16INK4a upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16INK4a upregulation. These results were supported by a meta‐analysis of 14 other similar studies regarding HPV‐transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.