Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.

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Global cancer statistics, 2012

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

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2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs). Reported TASs were common [median risk allele frequency 36%, interquartile range (IQR) 21%−53%] and were associated with modest effect sizes [median odds ratio (OR) 1.33, IQR 1.20–1.61]. Among 20 genomic annotation sets, reported TASs were significantly overrepresented only in nonsynonymous sites [OR = 3.9 (2.2−7.0), p = 3.5 × 10−7] and 5kb-promoter regions [OR = 2.3 (1.5−3.6), p = 3 × 10−4] compared to SNPs randomly selected from genotyping arrays. Although 88% of TASs were intronic (45%) or intergenic (43%), TASs were not overrepresented in introns and were significantly depleted in intergenic regions [OR = 0.44 (0.34−0.58), p = 2.0 × 10−9]. Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [OR = 1.3 (0.8−2.1), p = 0.2]. This new online resource, together with bioinformatic predictions of the underlying functionality at trait/disease-associated loci, is well-suited to guide future investigations of the role of common variants in complex disease etiology.

https://www.genome.gov/pages/about/od/newsandfeatures/pnasgwasonlinecatalog.pdf

Potential etiologic and functional implications of genome-wide association loci for human diseases and traits

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.)

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Abiraterone and Increased Survival in Metastatic Prostate Cancer

Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.

https://onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21149

Cancer treatment and survivorship statistics, 2012

© 2 0 0 7 T H E A U T H O R S 4 8 8 J O U R N A L C O M P I L A T I O N © 2 0 0 7 B J U I N T E R N A T I O N A L level of 3.0 ng/mL or lower. JAMA 2005; 294 : 66–70 9 Djavan B, Zlotta A, Remzi M et al. Optimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1051 men. J Urol 2000; 163 : 1144–9 10 Etzioni R, Penson DF, Legler JM et al. Overdiagnosis due to prostate-specific antigen screening: lessons from US prostate cancer incidence trends. JNCI 2002; 94 : 981–90 11 Draisma G, Boer R, Otto SJ et al. Lead times and overdetection due to prostatespecific antigen screening: Estimates from the European Randomized Study of Screening for Prostate Cancer. JNCI 2003; 95 : 868–78 12 Krahn MD, Mahoney JE, Eckman MH, Trachtenberg J, Pauker SG, Detsky AS. Screening for prostate cancer: a decision analytic view. JAMA 1994; 272 : 773– 80 13 Barry MJ, Fleming C, Coley CM, Wasson JH, Fahs MC, Oesterling JE. Should Medicare provide reimbursement for PSA testing for early detection of prostate cancer? IV. Management strategies and outcomes. Urology 1995; 46 : 445–61 14 Coley CM, Barry MJ, Fleming C, Fahs MC, Mulley AG. Clinical Guidelines: Part II. Early detection of prostate cancer. Part II: Estimating the risks, benefits, and costs. American College of Physicians. Ann Int Med 1997; 126 : 468–79 15 Cantor SB, Span SJ, Volk RJ et al. Prostate Cancer Screening: a decision analysis. J Fam Practice 1995; 41 : 33–41 16 Ross KS, Carter HB, Pearson JD, Guess HA. Comparative efficiency of PSA screening strategies for prostate cancer detection. JAMA 2000; 284 : 1399–405 17 Etzioni R, Cha R, Cowen ME. Serial prostate specific antigen screening for prostate cancer: a computer model evaluates competing strategies. J Urol 1999; 162 : 741–8 18 Ross KS, Guess HA, Carter HB. Estimation of treatment benefits when PSA screening for prostate cancer is discontinued at different ages. Urology 2005; 66 : 1038–42 19 Wright JC, Weinstein MC. Gains in life expectancy from medical interventions – standardizing data on outcomes. NEJM 1998; 339 : 380–6 Correspondence: Julia H Hayes, DanaFarber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA, USA. e-mail: Julia_Hayes@dfci.harvard.edu Abbreviations: DAM , decision-analytical modelling; LE , life-expectancy; QA(LY) , quality-adjusted (life-year).

A more selective approach to prostate biopsy could be a safe and effective form of prostate cancer ‘prevention’

Effects of radium-223 dichloride (Ra-223) on health-related quality of life (QOL) outcomes in the phase 3 ALSYMPCA study in patients with castration-resistant prostate cancer (CRPC) and bone metastases

Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy.DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years.Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C).The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited. 

Standard and hypofractionated dose escalation to intraprostatic tumour nodules in localised prostate cancer: 5 year efficacy and toxicity in the DELINEATE trial.

Chris Parker

Papers

A more selective approach to prostate biopsy could be a safe and effective form of prostate cancer ‘prevention’

Effects of radium-223 dichloride (Ra-223) on health-related quality of life (QOL) outcomes in the phase 3 ALSYMPCA study in patients with castration-resistant prostate cancer (CRPC) and bone metastases

Standard and hypofractionated dose escalation to intraprostatic tumour nodules in localised prostate cancer: 5 year efficacy and toxicity in the DELINEATE trial.

Use of radium-223 in men with metastatic castration-resistant prostate cancer.

1230 Effect of radium-233 dichloride (Ra-223) on hospitalization and its economic implications in ALSYMPCA trial