A standardized use of intraoperative anastomotic testing in colorectal surgery in the new millennium: is technology taking over? A systematic review and network meta-analysis.

BACKGROUND: Anastomotic leakage (AL) remains the most challenging complication following colorectal resection. There are several tests that can be used to test anastomotic integrity intraoperatively including air leak testing (ALT) and intraoperative colonoscopy (IOC). Indocyanine green (ICG) can be used to visualise blood supply to the bowel used in the anastomosis. However, there is no consensus internationally regarding routine use and which technique is superior. The aim of this study was to determine which intraoperative anastomotoic leak test (IALT) was most effective in reducing AL. METHODS: A systematic review and network meta-analysis were performed. An electronic systematic search was performed using Pubmed, CENTRAL, and Web of Science, of studies comparing ALT, IOC, and ICG. The inclusion criteria were as follows: (a) patients must have had colorectal surgery with formation of an anastomosis; (b) studies must have compared one or more IALTs; (c) and studies must have clear research methodology. RESULTS: Eleven articles totalling 3844 patients met the inclusion criteria and were included in this meta-analysis. Point estimation showed that the AL rate in the control group (no IALT) was significantly higher when compared to the ICG group (RR 0.44; Crl 0.14-0.87) and higher, but without reaching statistical significance, when compared to ALT (RR 0.53; Crl 0.21-1.30) and IOC (RR 0.49; Crl 0.10-1.80). Indirect comparison showed that the AL rate in the ICG group was lower, when compared to both ALT (RR 0.44; Crl 0.14-0.87) and IOC (RR 0.44; Crl 0.14-0.87). CONCLUSIONS: This study suggests that intraoperative testing for a good blood supply using ICG may reduce the AL rate following colorectal surgery.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

Nonsynonymous changes of equine lentivirus receptor-1 (ELR1) gene in amino acids involved in the interaction with equine infectious anemia virus (EIAV).

Equine lentivirus receptor-1 (ELR1) has been characterized as the specific functional receptor that mediates equine infectious anemia virus (EIAV) entrance to horse macrophages. This receptor is tumor necrosis factor receptor superfamily member 14 (TNFRSF14). The aim of this study was to investigate the occurrence of allelic variants in the coding sequence of equine TNFRSF14 gene by screening for single-nucleotide polymorphisms (SNPs) in different equine populations. Forty seven horse samples were randomly selected from a reservoir of EIAV-seropositive and seronegative samples collected from different outbreaks and regions of Argentina. DNA samples were scanned via PCR and direct sequencing of exon 3 and exon 5 of TNFRSF14 gene. A total of 21 SNPs were identified, of which 11 were located in coding sequences. Within exon 5, four SNPs caused nonsynonymous substitutions, while two other SNPs caused synonymous substitutions in crucial residues (Ser112 and Thr114) implicated in the interaction with EIAV. Despite some of exon 5 variants occurred exclusively in EIAV-positive or EIAV-negative horses, critical residues for the function of the mature protein were conserved, accounting for selective pressures in favor of preserving the specific function of TNFRSF members and the host immune response. To our knowledge, this is the first report of the existence of allelic variations involving some crucial amino acid residues in horse ELR1. Further, it could be an initial step to test the possible functional relevance and relationship of these variants with EIAV infection and disease progression as well as to develop preventive strategies.

Is abdominal CT useful for the management of patients with severe acute colitis complicating inflammatory bowel disease? A study in 54 consecutive patients.

AIM: To evaluate the contribution of CT for the management of patients with severe acute exacerbation of colitis (SAC) complicating inflammatory bowel disease (IBD); in particular, its contribution to surgical decision making. METHOD: All patients who were admitted to our institution for SAC complicating IBD were divided into two groups: group A (those who received surgical treatment); and group B (those who received medical treatment). Admission CT results were compared between groups. RESULTS: From 2006 to 2015, 54 patients [26 male; median age 39 (17-71) years] presenting with SAC were placed in either group A (n = 41; 76%) or group B (n = 13; 24%). Surgical patients in group A more frequently had altered general status (50 vs 17%; P = 0.01). Physical examination, Lichtiger score, endoscopic findings and laboratory results were similar between the groups. There was no significant difference in CT data between the groups with respect to extent of the colitis (pan-colitis in 54 and 69%, respectively, P = 0.35), median colonic thickness [10 (4-16) vs 8 (6-11) mm, P = 0.15], target enhancement (88 vs 77%, P = 0.38) and occurrence of toxic megacolon (2 vs 0%). CONCLUSION: Admission CT is not helpful in surgical decision making in SAC.

Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

Is it time to rethink the rule of total mesorectal excision? A prospective radiological and pathological study in 49 consecutive patients with mid-rectal cancer.

AIM: Total mesorectal excision (TME) after neoadjuvant chemoradiotherapy is the standard treatment for T3-T4 and/or N+ mid-rectal tumours, regardless of the exact tumour level. This leads to optimal oncological results but possible impaired functional results. Reducing rectal excision could reduce the functional drawbacks. This study prospectively assessed the risk of N+ or other mesorectal tumour deposit (OTD) below the tumour level by magnetic resonance imaging (MRI) performed after chemoradiotherapy and pathological examination of the TME specimen. METHOD: Consecutive patients with mid-rectal cancer who underwent TME after chemoradiotherapy were included. A prospective evaluation by postchemoradiotherapy MRI and pathological examination was performed to assess the location of N+ nodes and/or OTDs. RESULTS: Of 49 consecutive patients, 27 (55%) presented with nodes on postchemoradiotherapy MRI. However, only 12 nodes (size 2-4 mm) in 9 patients (18%) were under the tumour level. On pathological examination, 717 total lymph nodes were found, with 37 N+ and 22 OTD. According to the tumour level: (i) above tumour level, 21/453 nodes were N+ and 6 OTD; (ii) at tumour level, 16/166 nodes were N+ and 15 OTD; (iii) below tumour level, 0/98 nodes (0%) was N+ and only 1 OTD (2%) was noted at 2 cm below tumour level. CONCLUSION: After chemoradiotherapy, N+ and/or OTD located under the level of the rectal cancer seems to be a very rare event. A postchemoradiotherapy MRI could help detect such patients. For others patients, conservation of the lower rectum with only a subtotal mesorectal excision could possibly improve function.

MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

Cost-effectiveness of prostate cancer screening: a simulation study based on ERSPC data.

BACKGROUND: The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. METHODS: Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. RESULTS: Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. CONCLUSION: Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis.

[Uterine necrosis after arterial embolization for postpartum hemorrhage]. / Nécrose utérine après embolisation hémostatique des artères utérines.

Radiologic embolization of the uterine arteries is increasingly used to treat severe postpartum hemorrhage, as an alternative to surgical procedures. Guidelines have been published in order to standardize the indications as well as the technique. An important objective was to limit severe complications such as uterine necrosis. We report a case of a uterine necrosis after arterial embolization for severe postpartum hemorrhage due to uterine atony on a uterus with fibroids. This complication occurred despite the use of the recommended technique.

Can postoperative complications be predicted by a routine CT scan on day 5? A study of 78 laparoscopic colorectal resections.

BACKGROUND: Postoperative computed tomography (CT) scan patterns after colorectal resection are difficult to analyze for both clinicians and radiologists. This study aimed to assess the role of single CT scan on postoperative day 5 in predicting postoperative morbidity. METHODS: From October 2007 to August 2009, 78 patients undergoing laparoscopic colorectal resection were enrolled in a research study involving a routine contrast-enhanced multi-detector CT scan on postoperative day 5. Two groups were defined: patients with intra-abdominal postoperative morbidity requiring specific management, i.e., surgical or radiological procedure, and/or antibiotic therapy ("complications" group), and patients with uneventful postoperative outcome ("uneventful" group). CT findings were compared between the two groups with Fisher's exact test or chi-square test. RESULTS: Postoperative abdominal complications occurred in 16 patients (21 %). Of the CT findings on day 5, pneumonia, pulmonary embolism, portal or mesenteric thrombosis, operative area fat infiltration, peritoneal effusion, pneumoperitoneum, intra-abdominal collection, parietal inflammation or collection, and subcutaneous emphysema were observed in both groups without any significant difference. Only small bowel distension [25 % (4/16) in the "complications" group vs. 5 % (3/62) in the "uneventful" group; p = 0.029] and pleural effusion [81 % (13/16) vs. 48 % (30/62); p = 0.024, respectively] were observed significantly more often in the "complications" group. CONCLUSIONS: This study suggested that abdominal complications cannot be predicted by a CT scan on day 5 after laparoscopic colorectal resection. Thus, it cannot be recommended for routine use.

hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy.

BACKGROUND: The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+). methods: The study enrolled 1029 women with abnormal screening cytology (years 2006-2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006-2011). RESULTS: During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1-3.1) and 41.8% (95% CI 31.8-53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5-755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation. CONCLUSION: Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.

The cancer screening monitoring system: indicators for organised programmes and possible extension to spontaneous screening.

European Commission recommends the implementation of organized screening programs for cervical cancer based on active invitation of the target population and with a systematic monitoring system and quality assurance. Nevertheless, in many Member States opportunistic screening is still the only or the main way to access Pap test. In Italy, Pap test coverage in women aged 25-64 is close to 80%, about half of them are screened in organized programs and half by opportunistic screening. Organized programs are diffused in the vast majority of the country (78% in 2009) even if in some cases they are not able to actively invite all the target population every three years (actual extension 67%); furthermore, participation rate after invitation is quite low (39%). Organized screening programs showed performance indicators in line with most of the international standards: low referral rates (2.4%), low inadequate cytological results (4.7%), and high positive predictive value for high grade cervical intraepithelial neoplasia (16.2%). Opportunistic screening has no systematic monitoring system. The coexistence of the two screening models, organized programs and opportunistic, can be a source of inappropriate use of secondary prevention duplicating the tests and favoring deviations from recommended protocols. The Italian Ministry of Health recommends re-organizing cervical cancer prevention favoring organized programs or integrating spontaneous Pap testing in an organized system. To implement such integration it is necessary to have monitoring system and quality assurance for all providers and to integrate archives in order to avoid over-testing and deviation from protocols.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes.

OBJECTIVE: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. METHODS: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). RESULTS: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Mammographic screening programmes in Europe: organization, coverage and participation.

OBJECTIVES: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. METHODS: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. RESULTS: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. CONCLUSIONS: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Faecal occult blood testing.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on faecal occult blood testing includes 21 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.

FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3.

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide-platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide-platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide-platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide-platinum combination, 19 (49%; 12 women, median age 53 (29-78) years) received the FOLFIRI regimen with a median number of 6 (1-16) courses. Six patients (31%) had at least one episode of grades 3-4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide-platinum combination. These results should be confirmed in a future prospective study.

Does an organised screening programme reduce the inequalities in breast cancer survival?

BACKGROUND: The aim of the present study was to examine whether the implementation of an organised mammographic screening programme in Florence has been successful in reducing socioeconomic inequalities in breast cancer survival. PATIENTS AND METHODS: All invasive breast cancer cases diagnosed in women resident in the city of Florence in a prescreening period and in the first 10 years of the screening programme were selected. Their socioeconomic status (SES) was determined by using the national census 2001 data. All breast cancers were followed up to 10 years after the diagnosis. RESULTS: In the prescreening period, the survival of deprived women was 12 percentage points lower than the reference class, both in the younger age class (<50 years old) and in the age class target of the screening programme (50-69 years old). This difference progressively decreases until disappearing completely during the first 10 years of the screening programme for the age class invited to screening, whereas it remains stable in the younger age class. Participation in breast cancer screening and diagnostic accuracy were similar by SES. CONCLUSION: The organised breast cancer screening implemented in the Florentine area achieved the goal of reducing inequalities in breast cancer survival.

Changes in incidence, survival and mortality of prostate cancer in Europe and the United States in the PSA era: additional diagnoses and avoided deaths.

BACKGROUND: We describe changes in prostate cancer incidence, survival and mortality and the resulting impact in additional diagnoses and avoided deaths in European areas and the United States. METHODS: Using data from 12 European cancer registries and the Surveillance, Epidemiology and End Results program, we describe changes in prostate cancer epidemiology between the beginning of the PSA era (USA: 1985-1989, Europe: 1990-1994) and 2002-2006 among patients aged 40-64, 65-74, and 75+. Additionally, we examine changes in yearly numbers of diagnoses and deaths and variation in male life expectancy. RESULTS: Incidence and survival, particularly among patients aged <75, increased dramatically, yet both remain (with few exceptions in incidence) lower in Europe than in the United States. Mortality reductions, ongoing since the mid/late 1990 s, were more consistent in the United States, had a distressingly small absolute impact among patients aged 40-64 and the largest absolute impact among those aged 75+. Overall ratios of additional diagnoses/avoided deaths varied between 3.6 and 27.6, suggesting large differences in the actual impact of prostate cancer incidence and mortality changes. Ten years of remaining life expectancy was reached between 68 and 76 years. CONCLUSION: Policies reflecting variation in population life expectancy, testing preferences, decision aids and guidelines for surveillance-based management are urgently needed.