[Prostate cancer screening in France: Results from the EDIFICE surveys]. / Dépistage du cancer de la prostate en France : résultats des enquêtes EDIFICE.

INTRODUCTION: Prostate cancer (PCa) is the most common cancer amongst men in 2018 in Europe. The issue of PCa screening in the general population has been debated following the publication of international European (ERSPC) and North American (PLCO) studies. There is currently no organised PCa screening. The objective of this analysis was to evaluate the practice of PCa screening in the French population with no history of cancer between 2005 and 2016. METHODS: Since 2005, the EDIFICE surveys have focused on the knowledge and behaviour of French people with regard to cancer screening. The practice of screening was evaluated according to the answer to the question: "Have you ever done PCa screening?" Responses were analysed according to age, socio-professional category and level of social precariousness. RESULTS: After a strong increase between 2005 and 2008 (from 36% to 49%, P≤0.01), a significant decrease in the reported PCa screening rate was observed between 2014 (49%) and 2016 (42%; P=0.02). This decrease was mainly reflected in the socially advantaged categories and in the youngest age group (50-54 years). Screening practices remain the same in older men. CONCLUSION: The perception of the effectiveness of PCa screening could explain the changes of behavior in the French population. This decrease in participation in PCa screening requires monitoring to avoid a general loss of confidence in cancer screening. LEVEL OF EVIDENCE: 3.

Prostate cancer screening: contrasting trends.

PURPOSE: Our previously published data showed rapidly increasing rates of prostate cancer screening in men aged 50-74, which rose from 36% in 2005 to 48% in 2008. Based on men's reported intentions at that time, this was expected to rise to 70% in 2011. Here we report the actual rate of prostate cancer screening. METHOD: Three nationwide observational telephone surveys (EDIFICE opinion polls) were conducted in 2005, 2008, and 2011. The overall target was a representative sample of > 1,500 individuals living in France and aged 40-75 years, including 481 men aged 50-74 years. RESULTS: Within this male population, the rate of screening reported remained stable between 2008 and 2011 (48 and 49%, respectively). However, comparison of privileged versus disadvantaged populations showed significant differences, with a relative decrease in screening among those of higher socioprofessional status (p = 0.03) and from higher-income groups (p = 0.02). For households with a monthly income above 2,500€, the screening rate decreased from 61% in 2008 to 51% in 2011 (p = 0.05), while for those with an income below 2,500€, it increased from 36% in 2008 to 44 % in 2011 (p = 0.18). CONCLUSION: A plateau or even a reduction in prostate cancer screening is currently being observed; this is possibly due to progressive recognition among the population at large of the controversy surrounding prostate cancer screening, whereas this speculation was formerly limited to health-care professionals. After previously being more likely to undergo prostate cancer screening, it is the younger, wealthier populations that are currently showing the most noteworthy step backwards.

Melanoma risk-takers: fathers and sons.

OBJECTIVES: The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. METHODS: The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). RESULTS: Risk-takers were significantly more often male (62% vs. 44%, P < 0.01), had a lower level of education (40% vs. 26%, P < 0.01), lower incomes (2587 euros vs. 2948 euros/month) and were more often smokers (42% vs. 31%, P < 0.01). In contrast, age, marital status and use of sunbeds were not significantly different between the two groups. Interestingly, risk-takers had less risk factors for melanoma. However, they were less well-informed about high-risk exposure and optimal use of sunscreen. Sun-protection measures for their children were less stringent than those of the group who used sun protection: systematic/frequent use of sunglasses (42% vs. 59%, P < 0.01), systematic use of sunscreen (77% vs. 86%, P < 0.01), and frequent renewal (69% vs. 82%, P < 0.01), high sun protection factors (SPF) (46% vs. 56%, P < 0.01), use of clothing (84% vs. 92%, P < 0.01) and hats (88% vs. 94%, P < 0.01). CONCLUSIONS: Risk-takers are characterized by a lesser understanding of sun-protection measures and behaviours. Their children benefit less from protective measures than those of people who use sun protection themselves. Improved understanding may well improve behaviours; one can therefore legitimately predict a considerable impact on parents' attitude to their own protection and that of their children.

Colorectal liver metastases are more often super wild type. Toward treatment based on metastatic site genotyping?

Recent data showed that metastatic colorectal (mCRC) tumors exhibiting extended RAS-BRAF mutations were resistant to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, making these drugs suitable for the so-called "super" wild-type (WT) patients only. This study aimed to compare the extended RAS-BRAF mutation frequency and characteristics according to location of tumor sampling. All consecutive mCRC specimens (N = 1659) referred to our institution from January 2008 till June 2014 were included in the analysis. Tumor genotyping (first for KRAS exon 2, then for BRAF exon 15, and later for KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4) was performed with high-resolution melting analysis or allelic discrimination. The factors predicting for the presence of mutation were explored using multivariate binary logistic regression. Overall, the prevalence of KRAS exon 2 was 36.8%, and it was lower in liver metastases (N = 138/490; 28.2%) in comparison with primary tumors (N = 442/1086; 40.7%), lung metastases (16/32; 50%), or other metastatic sites (15/51; 29.4%; P < 0.0001). Similarly, in the 1428 samples analyzed, BRAF mutations were less often found in liver metastases (N = 9/396; 2.3%) as compared to primary tumors (N = 79/959; 8.2%), lung metastases (N = 2/29; 6.9%), or other metastatic locations (N = 2/44; 4.5%; P < 0.0002). Overall occurrence of extended RAS mutation was 51.7%. Of the 503 samples tested, the prevalence of extended RAS-BRAF mutations was twice as low in liver metastases (N = 53/151; 34.2 %) as compared to primary tumors (N = 191/322; 59.3%, P < 0.0001). Univariate analysis identified age ≤65 years, male gender, and liver localization as predictors of super WT status. At multivariate analysis, only liver metastases were retained (RR 2.85 [95% CI 1.91-4.30]). Colorectal liver metastases are twice as likely to exhibit a super WT genotype as compared to other tumor locations independently from other factors. This molecular feature has the potential to influence therapeutic strategy in mCRC patients.

Prognostic impact of microsatellite instability in colorectal cancer patients treated with adjuvant FOLFOX.

BACKGROUND: Colorectal cancer (CRC) patients whose tumours have microsatellite instability (MSI) do not benefit from adjuvant 5-fluorouracil. However, the predictive value of MSI is not known for FOLFOX, now recommended in adjuvant setting. PATIENTS AND METHODS: MSI phenotype was assessed by the pentaplex method. Three-year relapse and disease-free survival (DFS) of patients treated for CRC with FOLFOX 4 in an adjuvant setting were compared according to MSI phenotype. RESULTS: A total of 105 patients (19 MSI, 86 microsatellite stable, MSS) were included. Stage II patients more frequently exhibited MSI (58%) than MSS (21%); (p=0.002). Patients with MSI relapsed significantly less than those with MSS (10.5% vs. 35.0%; p=0.04). DFS was similar for MSI and MSS (p=0.1). In univariate analysis, stage (p=0.0006) and MSI status (p=0.017) were significant predictors of DFS. CONCLUSION: MSI status was associated with significantly fewer relapses and a better prognosis. FOLFOX4 did not alter survival of patients with MSI and can be administered to them.

[Single-center cohort study of elderly patients with surgically removed colorectal cancers]. / Patients agés opérés et pris en charge pour un cancer colorectal: etude d'une cohorte monocentrique.

Incidence of colorectal cancers (CRCs) increases with age. The surgical and medical management of elderly patients needs to be improved. Until recently, these patients were not included into controlled clinical trials. Between 2004 and 2007, 88 patients (median age 79) had surgery for CRC in our hospital. In half the cases, patients had an emergency surgery (40/88). Twenty patients had dementia, with no relationships between dementia and emergency surgery (50% vs. 45% for patients without dementia), nor between dementia and median length of hospital stay (16 days vs. 22 days). In metastatic setting (20 patients), chemotherapy was omitted in 10 cases, usually patients with dementia (5 patients; p = 0.002) Standard therapy was hardly applicable because many patients were frail. In the future, usefulness of participation to the staffs of a geriatrist will be assessed prospectively.

[Description of erlotinib-related skin effects management in France. Results of the PRECEDE study]. / Prise en charge des effets dermatologiques sous erlotinib. Résultats de l'étude PRECEDE.

INTRODUCTION: Dermatological effects are among the most frequent side-effects in patients receiving erlotinib (Tarceva). However, there no official recommendations on the preventive or curative management of those erlotinib-related skin effects (ERSE). The "Prise En Charge des Effets Dermatologiques sous Erlotinib" (PRECEDE) study was designed to study how ERSE are being managed in France. MATERIAL AND METHODS: The PRECEDE study is an observational retrospective study which included every nonsmall cell lung cancer patients treated with erlotinib in seven cancer centers in France from January 2005 to December 2007. Data related to preventive or curative treatment of ERSE were collected from the medical files of the patients. RESULTS: Two hundred and thirty-four patients were included; 48.7% of them had been delivered information on the potential occurrence of ERSE and 15.8% of those 234 patients had had prescription of drugs to be taken in case of ERSE, while 65.0% presented with ERSE which resolved in the majority of cases (86.2% of the patients), either spontaneously or under treatment. In the 85 patients in whom treatment was successful, 178 drug prescriptions comprising 35 different drugs were recorded. CONCLUSION: ERSE are frequent but regress in most cases, spontaneously or under treatment. However, there is still a wide variety of drugs used. This demonstrates that there is a need for recommendations on the management of ERSE in order to prevent and treat this erlotinib-related effect.

[Edifice program: analysis of screening exam practices for cancer in France]. / Le programme Edifice : analyse des pratiques de dépistage du cancer en France.

INTRODUCTION: The practices of screening and the parameters influencing these practices are not well known in France. The objectives of the Edifice study were to analyze a large cohort of patients and doctors in order to further characterize these parameters. PATIENTS AND METHODS: The study was performed by the Institute TNS Healthcare-SOFRES, and included 2 parallel studies: 1) on 1 609 healthy persons representative of the global French population and aged 40 to 75 years (N = 1 509), with an over representation of patients aged 50 to 74 years living in the 22 pilot French departments pilots; 2) on 600 generalist practitioners. Data were collected and analyzed by the expert panel... RESULTS: Ninety-three, 25, 36 and 6% of the patients in the general population declared to have performed at least one a screening exam for breast, colon, prostate, and lung carcinoma respectively. Seventy, 20, 60 and 4% of GP declare to propose systematically to a 40-75-year-old patient a screening test for breast, colon, prostate, or lung cancer. For breast cancer screening the adhesion of the GP is independent of the date of implementation of a general screening in their own regions, while for colorectal screening, 34 and 20% of the patients living in the pilot versus other departments were screened. Overall, prostate cancer screening is recommended by the GP panel for 77.1% of patients aged 50 to 75 years. CONCLUSIONS: This study shows a good adhesion of screening procedures for GP and patients, shows that screening is improved by general screening policy in colorectal cancer, but that prostate cancer screening practices exceed what is recommended according to evidence based medicine.

[Anemia and lung cancer]. / Anémie et cancer bronchique.

Erythopoietin (EPO) treatment of anemia during cancer has dramatically improved the tolerance of chemotherapy and quality of life of patients at all stages of the disease. Several surveys have demonstrated a high prevalence and a high incidence of anemia in lung cancer patients. The guidelines updates concerning EPO treatment for these patients are described. They take into account the debate concerning the potential harm of these molecules on the neoplastic disease and the possible role of EPO receptors expressed by several tumors, including non small cell lung cancer.

Identification of a functional EGF-R/p60c-src/STAT3 pathway in colorectal carcinoma: analysis of its long-term prognostic value.

AIMS: The Epidermal Growth Factor-Receptor (EGF-R) is frequently overexpressed in colorectal carcinoma (CRC) and patients can benefit from anti-EGF-R therapy. Yet, the relationship, within tumours, between EGF-R and the activity of downstream effectors such as the non-receptor tyrosine kinase p60c-src and the signal transducer and activator of transcription 3 (STAT3) has not been extensively analyzed. METHODS AND RESULTS: We evaluated EGF-R, tyrosine 416-phosphorylated p60c-src (P-p60c-src), STAT3 and tyrosine 705-phosphorylated STAT3 (P-STAT3) on Tissue Micro Array (TMA) from 126 patients with CRC. Composite immunohistochemistry scores based on the intensity of labelling and the percentage of positive cells were determined on TMA for EGF-R, P-p60c-src, STAT3 and P- STAT3. A high score was found in 56%, 61%, 62% and 27% of the cases for EGF-R, P-p60c-src, STAT3 and P-STAT3 respectively. There was a significant correlation between EGF-R and P-p60c-src (p=0.006) and between P-p60c-src and P-STAT3 (p=0.0009). STAT3 was significantly correlated with vascular emboli (p=0.03) and perineural invasion (p=0.02). CONCLUSIONS: The correlations between EGF-R, P-p60-src and P-STAT3 and some stage-related pathological features point to a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within CRC tumours.

Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer.

BACKGROUND: Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer. PATIENTS AND METHODS: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria. RESULTS: Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients. CONCLUSION: No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.

[Pulmonary metastases from endometrial stromal sarcoma may benefit from hormone therapy]. / Les métastases pulmonaires de sarcomes utérins peuvent bénéficier d'une hormonothérapie!

INTRODUCTION: Low grade endometrial stromal sarcoma (ESS) often expresses oestrogen (ER) and progesterone (PR) receptors, even in metastatic disease. These receptors may also be hormone dependent. CASE REPORT: Two years after the institution of oestrogen replacement therapy (HRT) a woman of 56 presented with haemoptysis which led to the discovery of multiple pulmonary nodules. Twelve years previously the patient had had a hysterectomy for a low grade endometrial stromal sarcoma, ER and PR positive. Surgical resection of the nodules on the right side confirmed the diagnosis of metastatic endometrial stromal sarcoma. The metastases expressed oestrogen and progesterone receptors. Three months after the withdrawal of HRT and treatment with an aromatase inhibitor (letrozole) the contralateral metastases had disappeared and this complete response was maintained for more than 2 years of follow-up. CONCLUSION: Care should be taken in the institution of HRT in a woman with a history of low grade ESS. Hormonal treatment with aromatase inhibitors may be considered in cases where ER and PR are expressed by the primary tumour and metastases, with possible benefits even in metastatic disease.

[What treatment for a patient of PS 2-3 with stage IV non-small cell lung cancer?]. / Quel traitement pour un patient de PS-2/3 ayant un cancer bronchique non à petites cellules (CBNPC) de stade IV?

Patients with poor performance status (PS) and advanced lung cancer have been underrepresented in clinical trials. As a consequence, the management of these patients in clinical practice is often empirical. Recent data indicate that patients with advanced non-small cell lung cancer (NSCLC) and a PS of 2 tend to benefit from first line chemotherapy with respect to symptom improvement and perhaps overall survival. Whether single-agent or combination chemotherapy is preferable remains debatable. In previously treated patients with NSCLC, EGFR tyrosine kinase inhibitors produced a substantial rate of clinical benefit and led to an improvement in survival compared with placebo in studies that included a significant percentage of patients with poor PS.

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature.

We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P < 0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

[Gefitinib treatment for carcinomatous meningitis in non-small cell lung cancer]. / Géfitinib et méningite carcinomateuse d'un carcinome bronchique non à petites cellules (CBNPC).

BACKGROUND: Carcinomatous meningitis is a major complication in Non Small Cell Lung Cancer (NSCLC). Despite treatment with radiotherapy alone or in combination with intrathecal and systemic chemotherapy, its prognosis remains poor. OBSERVATION: We report a case of a female non-smoker with adenocarcinoma with bronchoalveolar features presenting with carcinomatous meningitis three years after the diagnosis of her primary tumour. Gefitinib treatment was proposed because of the persistence of meningitic symptoms despite cranial irradiation. Clinical response was observed within 3 weeks and lasted for 9 months. CONCLUSION: Gefitinib may be effective in treating carcinomatous meningitis complicating NSCLC and should be considered in this situation given the absence of effective alternatives.

Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin.

BACKGROUND: This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine-docetaxel (GD) combination versus cisplatin-vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m(2) days 1 and 8 plus docetaxel 85 mg/m(2) day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m(2) day 1 plus vinorelbine 30 mg/m(2), days 1, 8, 15 and 22, every 4 weeks for six cycles). RESULTS: A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83-1.32], and for overall survival, it was 0.90 (95% CI 0.70-1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. CONCLUSIONS: There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.