Continuing declines in cancer mortality in the European Union

BACKGROUND: From 1988 to 1997 age-standardised total cancer mortality rates in the European Union (EU) fell by around 9% in both sexes. Available cancer mortality data in Europe up to 2002 allow a first check of the forecast of further declines in cancer mortality. PATIENTS AND METHODS: We considered trends in age-standardised mortality from major cancer sites in the EU during the period 1980-2002. RESULTS: For men, total cancer mortality, after a peak of 191.1/100,000 in 1987 declined to 177.8 in 1997 (-7%), and to 166.5 in 2002. Corresponding figures for females were 107.9/100,000, 100.5 and 95.2, corresponding to falls of 7% from 1987 to 1997, and to 5% from 1997 to 2002. Over the last 5 years, lung cancer declined by 1.9% per year in men, to reach 44.4/100,000, but increased by 1.7% in women, to reach 11.4. In 2002, for the first year, lung cancer mortality in women was higher than that for intestinal cancer (11.1/100,000), and lung cancer became the second site of cancer deaths in women after breast (17.9/100,000). From 1997 to 2002, appreciable declines were observed in mortality from intestinal cancer in men (-1.6% per year, to reach 18.8/100,000), and in women (-2.5%), as well as for breast (-1.7% per year) and prostate cancer (-1.4%). CONCLUSIONS: Despite the persisting rises in female lung cancer, the recent trends in cancer mortality in the EU are encouraging and indicate that an 11% reduction in total cancer mortality from 2000 to 2015 is realistic and possible.

Red meat and cancer risk in a network of case-control studies focusing on cooking practices.

BACKGROUND: Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. METHODS: We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. RESULTS: Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.

Childhood cancer mortality in America, Asia, and Oceania, 1970 through 2007.

BACKGROUND: Over the last 4 decades, childhood cancer mortality declined in most developed areas of the world. However, scant information is available from middle-income and developing countries. The authors analyzed and compared patterns in childhood cancer mortality in 24 developed and middle-income countries in America, Asia, and Oceania between 1970 and 2007. METHODS: Childhood age-standardized annual mortality rates were derived from the World Health Organization (WHO) database for all neoplasms, bone and kidney cancer, non-Hodgkin lymphoma (NHL), and leukemias. RESULTS: Since 1970, rates for all childhood cancers dropped from approximately 8 per 100,000 boys to 3 per 100,000 boys and from 6 per 100,000 girls to 2 per 100,000 girls in North America and Japan. Latin American countries registered rates of approximately 5 per 100,000 boys and 4 per 100,000 girls for 2005 through 2007, similar to the rates registered in more developed areas in the early 1980s. Similar patterns were observed for leukemias, for which the mortality rates were 0.81 per 100,000 boys and 0.55 per 100,000 girls in North America, 0.86 per 100,000 boys and 0.68 per 100,000 girls in Japan, and 1.98 per 100,000 boys and 1.65 per 100,000 girls in Latin America for 2005 through 2007. Bone cancer rates for 2005 through 2007 were approximately 2-fold higher in Argentina than in the United States. During the same period, Mexico registered the highest rate for kidney cancer and Colombia registered the highest rate for NHL, whereas the lowest rates were registered by Japan for kidney and by Japan and the United States for NHL. CONCLUSIONS: Improvements in the adoption of current integrated treatment protocols in Latin American and other lower- and middle-income countries worldwide would avoid a substantial proportion of childhood cancer deaths.

Osteolytic metastasis detected by F18-FDG PET in a patient with lung carcinoma

We present a 53-year-old man with a vocal cord paralysis observed as a primary manifestation of lung carcinoma. Tc-99m MDP whole body bone scan were performed and resulted a normal scintiscan. The bone scan does not revealed suspicious foci of uptake. The possibility of bone metastasis was taken into consideration. A whole body F18-FDG-PET scan showed intense uptake in the left upper lung corresponding to the primary tumor. A bronchial biopsy confirmed infiltration by small cell lung carcinoma (SCLC). SCLC is composed of poorly differentiated, rapidly growing cells with disease usually occurring centrally rather than peripherally. It metastasizes early. The whole-body F18-FDG-PET scan clearly demonstrated a focus of increased uptake in the second lumbar vertebral body suspicious for osteolytic metastasis. A lytic bone metastasis was confirmed by MRI. The patient then received therapy and underwent follow up abdominal CT. The scan showed blastic changes in the L2 vertebra suggesting response to treatment.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Family history of cancer and the risk of cancer: a network of case-control studies.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. CONCLUSIONS: Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.

Positron Emission Tomography and Computer Tomography (PET/CT) in Prostate, Bladder, and Testicular Cancers.

Positron emission computed tomography (PET) is a functional, noninvasive method for imaging regional metabolic processes that is nowadays most often combined to morphological imaging with computed tomography (CT). Its use is based on the well-founded assumption that metabolic changes occur earlier in tumors than morphologic changes, adding another dimension to imaging. This article will review the established and investigational indications and radiopharmaceuticals for PET/CT imaging for prostate cancer, bladder cancer and testicular cancer, before presenting upcoming applications in radiation therapy.

Endorectal Magnetic Resonance Imaging and Spectroscopy Are Useful for Selecting Candidates for Biopsy among Patients with Persistently Elevated Prostate Specific Antigen

To evaluate the efficacy of endorectal Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spetroscopic Imaging (MRSI) combined with total prostate-specific antigen (tPSA) and free prostate-specific antigen (fPSA) in selecting candidates for biopsy. Subjects and Methods: 246 patients with elevated tPSA (median: 7.81 ng/ml) underwent endorectal MRI and MRSI before Transrectal Ultrasound (TRUS) biopsy (10 peripheral + 2 central cores); patients with positive biopsies were treated with radical intention; those with negative biopsies were followed up and underwent MRSI before each additional biopsy if tPSA rose persistently. Mean follow-up: 27.6 months. We compared MRI, MRSI, tPSA, and fPSA with histopathology by sextant and determined the association between the Gleason score and MRI and MRSI. We determined the most accurate combination to detect prostate cancer (PCa) using receiver operating curves; we estimated the odds ratios (OR) and calculated sensitivity, specificity, and positive and negative predictive values. Results: No difference in tPSA was found between patients with and without PCa (p = 0.551). In the peripheral zone, the risk of PCa increased with MRSI grade; patients with high-grade MRSI had the greatest risk of PCa over time (OR = 328.6); the model including MRI, MRSI, tPSA, and fPSA was more accurate (Area under Curve: AUC = 95.7%) than MRI alone (AUC = 85.1%) or fPSA alone (AUC = 78.1%), but not than MRSI alone (94.5%). In the transitional zone, the model was less accurate (AUC = 84.4%). The association (p = 0.005) between MRSI and Gleason score was significant in both zones. Conclusions: MRSI is useful in patients with elevated tPSA. High-grade MRSI lesions call for repeated biopsies. Men with negative MRSI may forgo further biopsies because a significantly high Gleason lesion is very unlikely

The use of telomerase activity for the detection of prostatic cancer cells after prostatic massage.

PURPOSE: Prostate cancer is the most commonly diagnosed cancer in the United States. The diagnosis or followup of prostate cancer in men older than 50 years is based on digital rectal examination, measurement of the free-to-total prostatic specific antigen ratio and transrectal ultrasound assisted needle biopsy of the prostate. We developed and evaluated a noninvasive method for diagnosing prostate cancer based on the measurement of telomerase activity after prostatic massage in fresh voided urine or after urethral washing. MATERIALS AND METHODS: We obtained 36 specimens of cells after prostatic massage in the fresh voided urine of 16 patients who subsequently underwent radical prostatectomy and after urethral washing in 20 who underwent prostate needle biopsies. Ethylenediaminetetraacetic acid was immediately added to the collected urine or washing to a final concentration of 20 mM. After protein extraction by CHAPS buffer each specimen was tested for telomerase activity in a 2-step modified telomeric repeat amplification protocol assay. The 2 prostate cancer cell lines PC-3 and LNCaP with high telomerase activity were used as a positive control. RESULTS: Telomerase activity was detected in 14 of 24 samples with known prostate cancer (sensitivity 58%). In contrast, no telomerase activity was found in the 12 cases without histological evidence of prostate tumor (specificity 100%). Eight of 9 poorly differentiated cancers expressed telomerase activity (89%), while only 6 of 15 well and moderately differentiated cancers showed telomerase activity (40%). CONCLUSIONS: Our data illustrate that telomerase activity may be detected in voided urine or washing after prostatic massage in patients with prostate cancer. Sensitivity was higher for poorly differentiated tumors. This approach is not currently available for detecting prostate cancer in clinical practice. However, these results are promising and further studies are ongoing.

European cancer mortality predictions for the year 2015 : does lung cancer have the highest death rate in EU women?

BACKGROUND: Cancer mortality statistics for 2015 were projected from the most recent available data for the European Union (EU) and its six more populous countries. Prostate cancer was analysed in detail. PATIENTS AND METHODS: Population and death certification data from stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukaemias and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected 2015 numbers of deaths by age group were obtained by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: A total of 1 359 100 cancer deaths are predicted in the EU in 2015 (766 200 men and 592 900 women), corresponding to standardised death rates of 138.4/100 000 men and 83.9/100 000 women, falling 7.5% and 6%, respectively, since 2009. In men, predicted rates for the three major cancers (lung, colorectum and prostate) are lower than in 2009, falling 9%, 5% and 12%. Prostate cancer showed predicted falls of 14%, 17% and 9% in the 35-64, 65-74 and 75+ age groups. In women, breast and colorectal cancers had favourable trends (-10% and -8%), but predicted lung cancer rates rise 9% to 14.24/100 000 becoming the cancer with the highest rate, reaching and possibly overtaking breast cancer rates-though the total number of deaths remain higher for breast (90 800) than lung (87 500). Pancreatic cancer has a negative outlook in both sexes, rising 4% in men and 5% in women between 2009 and 2015. CONCLUSIONS: Cancer mortality predictions for 2015 confirm the overall favourable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 21% in women, and the avoidance of over 325 000 deaths in 2015 compared with the peak rate.

Identifying the index lesion with template prostate mapping biopsies.

PURPOSE: The natural history of prostate cancer might be driven by the index lesion. We determined the percent of men in whom the index lesion could be defined using transperineal template prostate mapping biopsies. MATERIALS AND METHODS: Included in study were consecutive men undergoing transperineal template prostate mapping biopsies with biopsies grouped into 20 zones. Men with clinically significant disease in only 1 prostate area were considered to have an identifiable index lesion. We evaluated the impact of using 2 definitions of clinically significant disease (Gleason grade pattern 4 and/or lesion volume 0.5 cc or greater) and 2 clustering rules (stringent and tolerant) to define the index lesion. RESULTS: Included in study were 391 men with a median age of 62 years (IQR 58-67) and a median prostate specific antigen of 6.9 ng/ml (IQR 4.8-10.0). Of the men 269 (69%) were previously diagnosed with prostate cancer. By deploying a median of 1.2 cores per ml (IQR 0.9-1.7) cancer was diagnosed in 82.9% of the men (324 of 391) with a median of 6 positive cores (IQR 2-9), a median maximum cancer core length of 5 mm (IQR 3-8) and a total cancer core length per zone of 7 mm (IQR 3-13). Insignificant disease was found in 26.3% to 42.9% of cases. When a stringent spatial relationship was used to define individual lesions, 44.4% to 54.6% of patients had 1 index lesion and 12.7% to 19.1% had more than 1 area with clinically significant disease. These proportions changed to 46.6% to 59.2% and 10.5% to 14.5%, respectively, when less stringent spatial clustering was applied. CONCLUSIONS: Transperineal template prostate mapping biopsies enable the index lesion to be localized in most men with clinically significant disease. This information may be important to select appropriate candidates for targeted therapy and to plan a tailored treatment strategy in men undergoing radical therapy.

Global surveillance of cancer survival 1995-2009 : analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts

Dose-escalated radiation therapy for localized prostate cancer (PCa) has a clear therapeutic benefit; however, escalated doses may also increase injury to noncancerous tissues. Radiosensitizing agents can improve ionizing radiation (IR) potency, but without targeted delivery, these agents will also sensitize surrounding normal tissues. Here we describe the development of prostate-targeted RNAi agents that selectively sensitized prostate-specific membrane antigen–positive (PSMA-positive) cells to IR. siRNA library screens identified DNA-activated protein kinase, catalytic polypeptide (DNAPK) as an ideal radiosensitization target. DNAPK shRNAs, delivered by PSMA-targeting RNA aptamers, selectively reduced DNAPK in PCa cells, xenografts, and human prostate tissues. Aptamer-targeted DNAPK shRNAs, combined with IR, dramatically and specifically enhanced PSMA-positive tumor response to IR. These findings support aptamer-shRNA chimeras as selective sensitizing agents for the improved treatment of high-risk localized PCa.

European cancer mortality predictions for the year 2016 with focus on leukemias.

BACKGROUND: Current cancer mortality statistics are important for public health decision making and resource allocation. Age standardized rates and numbers of deaths are predicted for 2016 in the European Union. PATIENTS AND METHODS: Population and death certification data for stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukemia and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected numbers of deaths by age group were obtained for 2016 by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: Projected total cancer mortality trends for 2016 in the EU are favourable in both sexes with rates of 133.5/100,000 men and 85.2/100,000 women (8% and 3% falls since 2011, due to population ageing) corresponding to 753,600 and 605,900 deaths in men and women for a total number of 1,359,500 projected cancer deaths (+3% compared to 2011). In men lung, colorectal and prostate cancer fell 11%, 5% and 8% since 2011. Breast and colorectal cancer trends in women are favourable (8% and 7% falls, respectively), but lung and Pancreatic cancer rates rose 5% and 4% since 2011 reaching rates of 14.4 and 5.6/100,000 women. Leukemia shows favourable projected mortality for both sexes and all age groups with stronger falls in the younger age groups, rates are 4.0/100,000 men and 2.5/100,000 women, with respectively falls of 14% and 12%. CONCLUSION: The 2016 predictions for EU cancer mortality confirm the favourable trends in rates particularly for men. Lung cancer is likely to remain the leading site for female cancer rates. Continuing falls in mortality, larger in children and young adults, are predicted in leukemia, essentially due to advancements in management and therapy, and their subsequent adoption across Europe.

Multiparametric magnetic resonance imaging of the prostate: current concepts

Multiparametric MR (mpMR) imaging is rapidly evolving into the mainstay in prostate cancer (PCa) imaging. Generally, the examination consists of T2-weighted sequences, diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) evaluation, and less often proton MR spectroscopy imaging (MRSI). Those functional techniques are related to biological properties of the tumor, so that DWI correlates to cellularity and Gleason scores, DCE correlates to angiogenesis, and MRSI correlates to cell membrane turnover. The combined use of those techniques enhances the diagnostic confidence and allows for better characterization of PCa. The present article reviews and illustrates the technical aspects and clinical applications of each component of mpMR imaging, in a practical approach from the urological standpoint.