Did the COVID-19 pandemic delay treatment for localized breast cancer patients? A multicenter study.

BACKGROUND: Longer times between diagnosis and treatments of cancer patients have been estimated as effects of the COVID-19 pandemic. However, relatively few studies attempted to estimate actual delay to treatment at the patient level. OBJECTIVE: To assess changes in delays to first treatment and surgery among newly diagnosed patients with localized breast cancer (BC) during the COVID-19 pandemic. METHODS: We used data from the PAPESCO-19 multicenter cohort study, which included patients from 4 French comprehensive cancer centers. We measured the delay to first treatment as the number of days between diagnosis and the first treatment regardless of whether this was neoadjuvant chemotherapy or surgery. COVID-19 pandemic exposure was estimated with a composite index that considered both the severity of the pandemic and the level of lockdown restrictions. We ran generalized linear models with a log link function and a gamma distribution to model the association between delay and the pandemic. RESULTS: Of the 187 patients included in the analysis, the median delay to first treatment was 42 (IQR:32-54) days for patients diagnosed before and after the start of the 1st lockdown (N = 99 and 88, respectively). After adjusting for age and centers of inclusion, a higher composite pandemic index (> = 50 V.S. <50) had only a small, non-significant effect on times to treatment. Longer delays were associated with factors other than the COVID-19 pandemic. CONCLUSION: We found evidence of no direct impact of the pandemic on the actual delay to treatment among patients with localized BC.

Long-term Outcomes and Patterns of Relapse Following High-dose Elective Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Nodes in Prostate Cancer: OLIGOPELVIS (GETUG-P07).

Androgen deprivation therapy (ADT) is a mainstay of treatment for metastatic prostate cancer, while additional salvage radiotherapy may offer prolonged remission for patients with regional node relapses. We report 5-yr outcomes from OLIGOPELVIS (GETUG-P07), an open-label phase 2 trial assessing long-term outcomes and patterns of relapse after 6-mo ADT and elective nodal radiotherapy (ENRT) in men with pelvic nodal oligorecurrence (<6 lesions) of prostate cancer. Progression was defined as two consecutive prostate-specific antigen (PSA) levels above the level at inclusion and/or clinical progression according to Response Evaluation Criteria in Solid Tumors v1.1 and/or death from any cause. Sixty-seven patients were recruited. Median follow-up was 6.1 yr (95% confidence interval 5.9-6.3). Rates of grade 2+ toxicities among patients without progression at 3, 4, and 5 yr were 15%, 9%, and 4% for genitourinary toxicities, and 2%, 3%, and 4% for gastrointestinal toxicities, respectively. The 5-yr progression-free, biochemical relapse-free, and ADT-free survival rates were 39%, 31%, and 64%, respectively. In total, 45 patients experienced progression, which was PSA-only progression in seven cases. Among the other 38 patients, local clinical progression occurred in 18%, progression to N1 stage in 29%, to M1a stage in 50%, to M1b stage in 32%, and to M1c stage in 11%. Finally, combined ENRT and ADT appeared to prolong tumor control with limited toxicity. At 5 yr, one-third of the patients had not experienced biochemical relapse. The major site of relapse was the para-aortic lymph nodes. PATIENT SUMMARY: We evaluated long-term results for high-dose radiotherapy in patients with recurrence of prostate cancer in pelvic lymph nodes. We found that this treatment provided prolonged tumor control without significant toxicity. One-third of the patients were still in complete remission after 5 years.

COVID-19 Infection despite Previous Vaccination in Cancer Patients and Healthcare Workers: Results from a French Prospective Multicenter Cohort (PAPESCO-19).

In a multicenter prospective cohort of cancer patients (CP; n = 840) and healthcare workers (HCWs; n = 935) vaccinated against COVID-19, we noticed the following: i/after vaccination, 4.4% of HCWs and 5.8% of CP were infected; ii/no characteristic was associated with post-vaccine COVID-19 infections among HCWs; iii/CP who developed infections were younger, more frequently women (NS), more frequently had gastrointestinal, gynecological, or breast cancer and a localized cancer stage; iv/CP vaccinated while receiving chemotherapy or targeted therapy had (NS) more breakthrough infections after vaccination than those vaccinated after these treatments; the opposite was noted with radiotherapy, immunotherapy, or hormonotherapy; v/most COVID-19 infections occurred either during the Alpha wave (11/41 HCW, 20/49 CP), early after the first vaccination campaign started, or during the Omicron wave (21/41 HCW, 20/49 CP), more than 3 months after the second dose; vi/risk of infection was not associated with values of antibody titers; vii/the outcome of these COVID-19 infections after vaccination was not severe in all cases. To conclude, around 5% of our CPs or HCWs developed a COVID-19 infection despite previous vaccination. The outcome of these infections was not severe.

Randomized phase II trial in prostate cancer with hormone-sensitive OligometaSTatic relapse: Combining stereotactic ablative radiotherapy and durvalumab (POSTCARD GETUG P13): Study protocol.

Background: As in other solid tumors, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis than patients with extensive metastatic disease. Stereotactic body radiotherapy (SBRT) is now considered an option in this population.Programmed death-1 (PD-1) and its ligands (PD-L1) are targeted by immune checkpoint inhibitors. Preclinical studies have shown that the tumor immune microenvironment changes when combining radiotherapy with immunotherapy, especially with hypofractionated radiotherapy.The oligometastatic setting appears to be the most relevant clinical situation for evaluating the immune response generated by radiotherapy and immune checkpoint inhibitors in patients with an intact immune system.We hypothesize that durvalumab will enhance the immune response following SBRT targeting oligometastatic lesions. Our purpose is to demonstrate, via a randomized 2:1 phase II trial, that SBRT (3 fractions) with durvalumab in oligometastatic hormone-sensitive prostate cancer patients would improve progression-free survival in patients with prostate cancer with up to 5 metastases compared to patients who exclusively received SBRT. Methods: This is a multicentric randomized phase II study in French academic hospitals. Patients with prostate cancer and up to 5 metastases (lymph node and/or bone) were randomized into a 2:1 ratio between Arm A (experimental group), corresponding to durvalumab and SBRT to the metastases, and Arm B (control group), corresponding to SBRT alone to the metastases. The study aims to accrue a total of 96 patients within 3 years. The primary endpoint is two-year progression-free survival and secondary endpoints include androgen deprivation therapy-free survival, quality of life, toxicity, prostate cancer specific survival, overall survival, and immune response. Discussion: The expected benefit for the patients in the experimental arm is longer life expectancy with acceptable toxicity. We also expect our study to provide data for better understanding the synergy between immunotherapy and radiotherapy in oligometastatic prostate cancer.

COVID-19 Vaccination Campaign in Cancer Patients and Healthcare Workers-Results from a French Prospective Multicenter Cohort (PAPESCO-19).

In this prospective, real-life cohort study, we followed 523 cancer patients (CP) and 579 healthcare workers (HCW) from two cancer centers to evaluate the biological and clinical results of the COVID-19 vaccination campaign. Seventy percent of the CP and 90% of the HCW received an mRNA vaccine or the AZD1222 vaccine. Seropositivity was high after the first vaccine among HCW and poor among CP. The second dose resulted in almost 100% seropositivity in both cohorts. Antibody response was higher after the second injection than the first in both populations. Despite at least two doses, 8 CP (1.5%) and 14 HCW (2.4%) were infected, corresponding either to a weak level of antibody or a new strain of virus (particularly the Omicron variant of concern). Sixteen CP and three HCW were hospitalized but none of them died from COVID-19. To conclude, this study showed that two doses of COVID-19 vaccines were crucially necessary to attain sufficient seropositivity. However, the post-vaccination antibody level declines in individuals from the two cohorts and could not totally prevent new SARS-CoV-2 infections.

COVID-19 Infections in Cancer Patients Were Frequently Asymptomatic: Description From a French Prospective Multicenter Cohort (PAPESCO-19).

Background: Cancer patients (CPs) are considered more vulnerable and as a high mortality group regarding COVID-19. In this analysis, we aimed to describe asymptomatic COVID (+) CPs and associated factors. Methods: We conducted a prospective study in CPs and health care workers (HCWs) in 4 French cancer centers (PAPESCO [PAtients et PErsonnels de Santé des Centres de Lutte Contre le Cancer pendant l'épidémie de COvid-19] study). This analysis used data recorded between June 17, 2020 and November 30, 2020 in CPs (first 2 waves, no variants). At inclusion and quarterly, CPs reported the presence of predefined COVID-19 symptoms and had a blood rapid diagnostic test; a reverse transcription polymerase chain reaction (RT-PCR) was done in case of suspected infection. Results: A total 878 CPs were included; COVID-19 prevalence was similar in both CPs (8%) and HCWs (9.5%); of the 70 CPs (8%) who were COVID (+), 29 (41.4%) were and remained asymptomatic; 241/808 of the COVID (-) (29.8%) were symptomatic. 18 COVID (+) were hospitalized (2% of CPs), 1 in intensive care unit (ICU) and 1 died (0.1% of CPs and 2.4% of symptomatic COVID [+] CPs). Only the inclusion center was associated with clinical presentation (in Nancy, Angers, Nantes, and Clermont-Ferrand: 65.4%, 35%, 28.6%, and 10% CPs were asymptomatic, respectively). Conclusions: Seroprevalence of COVID-19 in CPs was similar to that observed in HCWs; mortality related to COVID-19 among CPs was 0.1%. More than 40% of COVID (+) CPs were asymptomatic and one third of COVID (-) CPs had symptoms. Only geographic origin was associated with the presence or absence of symptoms. Social distancing and protective measures must be applied in CPs at home and when hospitalized.

OLIGOPELVIS GETUG P07, a Multicenter Phase II Trial of Combined High-dose Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Node Relapses in Prostate Cancer.

BACKGROUND: Oligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses. OBJECTIVE: To assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause. RESULTS AND LIMITATIONS: Between August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse-free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively. CONCLUSIONS: Combined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result. PATIENT SUMMARY: In this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity.

Anosmia but Not Ageusia as a COVID-19-Related Symptom among Cancer Patients-First Results from the PAPESCO-19 Cohort Study.

Background: Cancer patients may fail to distinguish COVID-19 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, and fatigue, which are frequent after cancer treatments. We aimed to identify symptoms associated with COVID-19 and to assess the strength of their association in cancer and cancer-free populations. Methods: The multicenter cohort study PAPESCO-19 included 878 cancer patients and 940 healthcare workers (HCWs). At baseline and quarterly thereafter, they reported the presence or absence of 13 COVID-19 symptoms observed over 3 months and the results of routine screening RT-PCR, and they were systematically tested for SARS-CoV-2-specific antibodies. We identified the symptom combinations significantly associated with COVID-19. Results: Eight percent of cancer patients were COVID-19 positive, and 32% were symptomatic. Among the HCWs, these proportions were 9.5 and 52%, respectively. Anosmia, anorexia, fever, headache, and rhinorrhea together accurately discriminated (c-statistic = 0.7027) COVID-19 cases from cancer patients. Anosmia, dysgeusia/ageusia, muscle pain, intense fatigue, headache, and chest pain better discriminated (c-statistic = 0.8830) COVID-19 cases among the HCWs. Anosmia had the strongest association in both the cancer patients (OR = 7.48, 95% CI: 2.96-18.89) and HCWs (OR = 5.71, 95% CI: 2.21-14.75). Conclusions: COVID-19 symptoms and their diagnostic performance differ in the cancer patients and HCWs. Anosmia is associated with COVID-19 in cancer patients, while dysgeusia/ageusia is not. Cancer patients deserve tailored preventive measures due to their particular COVID-19 symptom pattern.

Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases.

(1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; "iPET") in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using 18F-deoxyglucose (FDG) for BC or 18F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.

A phase I dose-escalation study of oxaliplatin delivered via a laparoscopic approach using pressurised intraperitoneal aerosol chemotherapy for advanced peritoneal metastases of gastrointestinal tract cancers.

OBJECTIVE: The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers. METHODS: PIPAC was applied every 4-6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m2 with planned increases of 50 mg/m2 per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov (NCT03294252). RESULTS: Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m2 and two at 140 mg/m2. The MTD was therefore set at 90 mg/m2. Overall treatment included a median number of three PIPAC sessions (range: 1-5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I-II and 11 grade III-IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m2, the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC)0-48h of 1035 µg/l and 9028 µg h/L, respectively. CONCLUSIONS: The MTD of oxaliplatin during PIPAC is 90 mg/m2. PK data demonstrate a high tumour concentration and a significant systemic absorption.

Occupational exposure to benzene, toluene, xylene and styrene and risk of prostate cancer in a population-based study.

OBJECTIVES: While several monocyclic aromatic hydrocarbons are classified as definite or possible carcinogens to humans, little data exist on their role in prostate cancer (PCa). We examined occupational exposure to benzene, toluene, xylene (BTX) and styrene and PCa risk in a population-based case-control study in Montreal, Canada. METHODS: Cases aged ≤75 years diagnosed with PCa in 2005-2009 (n=1920) and population controls frequency-matched on age (n=1989) provided detailed work histories. Experts evaluated the certainty, frequency and concentration of exposure to monocyclic aromatic hydrocarbons in each job lasting ≥2 years. Logistic regression estimated OR and 95% CIs for PCa risk, adjusting for potential confounders. RESULTS: Exposures to BTX were highly intercorrelated, except for durations of exposure at substantial levels. Ever exposure to any BTX was associated with overall PCa (OR 1.27, 95% CI 1.05 to 1.53), while the OR for styrene was 1.19. However, increases in risk were largely confined to low-grade tumours, with ORs of 1.33 (95%CI 1.08 to 1.64) and 1.41 (95% CI 0.85 to 2.31) for ever exposure to any BTX and styrene, respectively, and a duration response pattern for any BTX. Risks for low-grade tumours were elevated among men exposed ≥25 years at substantial levels of benzene (OR 2.32) and styrene (OR 2.44). Some cumulative exposure categories showed increased risks but without clear trends. CONCLUSION: Exposure to any BTX was associated with higher risks of overall PCa. Prolonged exposures at the substantial level to benzene and styrene increased risks of low-grade tumours. These novel findings were independent from PCa screening.

Perceived Workplace Stress Is Associated with an Increased Risk of Prostate Cancer before Age 65.

BACKGROUND: Evidence is lacking regarding the potential role of chronic psychological stress on cancer incidence. The workplace is reported to be the main source of stress among Canadian men. We examined the association between perceived lifetime workplace stress and prostate cancer (PCa) risk in a large case-control study. METHODS: Cases were 1,933 men, aged ≤ 75 years, newly diagnosed with PCa in 2005-2009 across hospitals in Montreal, Canada. Concurrently, 1994 population controls frequency-matched on age were randomly selected from the electoral list based on cases' residential districts. Detailed lifestyle and work histories (including perceived stress, from any type of work stressor, for each job held) were collected during in-person interviews. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between work-related stress and PCa risk in multivariate analyses. RESULTS: Over the lifetime, 58% of subjects reported at least one job as stressful. Occupations described as stressful were most often among white-collar workers. Perceived workplace stress duration was associated with a higher risk of PCa (OR = 1.12, 95% CI:1.04-1.20 per 10-year increase) among men younger than 65 years, but not among older men. Associations were similar irrespective of PCa aggressiveness. Frequent or recent screening for PCa, age at first exposure and time since exposure to work-related stress, and socioeconomic and lifestyle factors, had little influence on risk estimates. CONCLUSION: Findings are in line with an association between reporting prolonged workplace stress and an increase in risk of PCa before age 65.

Lifetime report of perceived stress at work and cancer among men: A case-control study in Montreal, Canada.

BACKGROUND: The association between perceived workplace psychological stress, over the entire work career, and cancer among men has never been assessed. This was explored in the context of a population-based case-control study conducted in Montreal, Canada. METHODS: 3103 incident cancer cases (11 types) diagnosed in 1979-1985 and 512 population controls were interviewed. Subjects described in detail each job held during their lifetime, including the occurrence of stress, and its reason. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between perceived workplace stress and its duration, and each cancer site, adjusting for lifestyle and occupational factors. RESULTS: Employment in at least one stressful job was associated with increased odds of cancers of the lung (OR=1.33, 95% CI: 1.01-1.75), colon (OR=1.51, 95% CI: 1.15-1.98), bladder (OR=1.37, 95% CI: 1.03-1.81), rectal (OR=1.52, 95% CI: 1.10-2.10), and stomach (OR=1.53, 95% CI: 1.08-2.15). A duration-response trend was found for cancers of the lung, colon, rectum, stomach, and for NHL. Subjects reported changes in stress level over their career. Perceived stress was ascribed to several sources, including high demand and time pressure, financial issues, job insecurity, and hazardous conditions. CONCLUSION: Prolonged exposure to perceived stress at work was associated with greater odds of cancer at 5 out of 11 sites. While over reporting of stress by cases cannot be fully ruled out, these associations, if substantiated, would bear important public health significance. Prospective studies building on detailed stress assessment protocols considering all sources and changes over the career are necessary.

A French crop-exposure matrix for use in epidemiological studies on pesticides: PESTIMAT.

Pesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals' report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose-effect relationships, an important criterion for causality judgment in epidemiology.

Metabolic syndrome and prostate cancer risk in a population-based case-control study in Montreal, Canada.

BACKGROUND: The role of metabolic syndrome (MetS) in prostate cancer risk is still debated. We investigated it in a large population-based case-control study. METHODS: Cases were 1937 men with incident prostate cancer, aged ≤ 75 years, diagnosed across French hospitals in the Montreal area between 2005 and 2009. Concurrently, 1995 population controls from the same residential area and age distribution were randomly selected from electoral list of French-speaking men. Detailed lifestyle and medical histories, and anthropometric measures, were collected during in-person interviews. Prevalence of MetS components (type 2 diabetes, high blood pressure, dyslipidemia and abdominal obesity) was estimated at 2 years before diagnosis for cases/ interview for controls, and at ages 20, 40, 50 and 60. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals for the association between MetS and prostate cancer risk. RESULTS: A history of MetS (≥ 3 components vs < 3) was associated with a reduced risk of prostate cancer (OR = 0.70 [0.60, 0.82]) after considering potential confounders. The negative association was particularly pronounced with a young age (≤ 40 years) at MetS onset (OR = 0.38 [0.16-0.89]), did not vary according to prostate cancer aggressiveness, and was only partly explained by the presence of type 2 diabetes. A risk decrease was observed with the number of MetS components, suggesting a synergistic interaction of the components. DISCUSSION: The observed negative association, consistent with results from other North American populations undergoing regular prostate cancer screening, underlines the importance of considering PSA-testing when studying the MetS-prostate cancer association. CONCLUSIONS: Findings from this study are consistent with an inverse association between MetS and prostate cancer risk.

Waist circumference, waist-hip ratio, body mass index, and prostate cancer risk: results from the North-American case-control study Prostate Cancer & Environment Study.

INTRODUCTION: The evidence on the association between anthropometric measures quantifying body fatness and prostate cancer (PCa) risk is not entirely consistent. Associations among waist circumference (WC), waist-hip ratio, body mass index (BMI), and PCa risk were assessed in a population-based case-control study. PATIENTS AND METHODS: The study included 1933 incident PCa cases diagnosed between 2005 and 2009. Population controls were 1994 age-matched (±5y) Montreal residents selected from electoral lists. Information on sociodemographics, medical history including PCa screening, height, weight, and waist and hip circumferences was collected through interviews. Logistic regression was used to assess odds ratios (ORs) for the association between anthropometric measures, and overall and grade-specific PCa. RESULTS: After adjustment for BMI, an excess risk of high-grade PCa (Gleason≥7) was associated with a WC ≥102cm (OR = 1.47 [1.22-1.78]) and with a waist-hip ratio >1.0 (OR = 1.20 [1.01-1.43]). Men with a BMI≥30kg/m(2) had a lower risk of PCa, regardless of grade. Restricting to subjects recently screened for PCa did not alter findings. CONCLUSION: Elevated BMI was associated with a lower risk of PCa, regardless of grade. Contrastingly, abdominal obesity, when adjusted for BMI, yielded results in the opposite direction. Taken together, our observations suggest that the specific body fat distribution (abdominal), for a given BMI, is a predictor of PCa risk, whereas BMI alone is not. BMI and abdominal obesity, especially when measured by the WC, should be examined conjointly in future studies on this issue and may require consideration at patient counseling.

BPH: a tell-tale sign of prostate cancer? Results from the Prostate Cancer and Environment Study (PROtEuS).

INTRODUCTION: In a population-based case-control study (PROtEuS), we examined the association between prostate cancer (PCa) and (1) benign prostatic hypertrophy (BPH) history at any time prior to PCa diagnosis, (2) BPH-history reported at least 1 year prior to interview/diagnosis (index date) and (3) exposure to BPH-medications. METHODS: Cases were 1933 men with incident prostate cancer diagnosed across Montreal French hospitals between 2005 and 2009. Population controls were 1994 men from the same age distribution and residential area. In-person interviews collected socio-demographic characteristics and medical history, e.g., BPH diagnosis, duration and treatment, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. RESULTS: A BPH-history was associated with an increased risk of PCa (OR 1.37 [95 % CI 1.16-2.61]), more pronounced for low-grade PCa (Gleason ≤6: OR 1.54 [1.26-1.87]; Gleason ≥7: OR 1.05 [0.86-1.27]). The association was not significant when BPH-history diagnosis was more than 1 year prior to index date, except for low-grade PCa (OR 1.29 [1.05-1.60]). Exposure to 5α reductase inhibitors (5α-RI) resulted in a decreased risk of overall PCa (OR 0.62 [0.42-0.92]), particularly for intermediate- to high-grade PCa (Gleason ≤6: OR 0.70 [0.43-1.14]; Gleason ≥7: OR 0.43 [0.26-0.72]). Adjusting for PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. CONCLUSION: BPH-history was associated with an increased PCa risk, which disappeared, when BPH-history did not include BPH diagnosis within the previous year. Our results also suggest that 5α-RI exposure exerts a protective effect on intermediate and high-grade PCa.

Use of oral anticoagulants and risk of prostate cancer: a population-based case-control study in Montreal, Canada.

PURPOSE: A few recent epidemiological observations suggest that anticoagulant medications may protect against prostate cancer development. Most studies have been small or subjected to methodological issues, including potential confounding. We provide here new evidence on this association in the context of a population-based case-control study of prostate cancer conducted in Montreal, Canada. METHODS: Cases were 1,588 men with incident prostate cancer, aged ≤75 years, diagnosed across French hospitals in the Montreal area between 2005 and 2009. Concurrently, 1,618 population controls from the same residential area and age distribution (±5 years) were randomly selected from the electoral list of French-speaking men. In-person interviews elicited information on socio-demographic, lifestyle and environmental factors, along with a detailed medical history. Unconditional logistic regression was used to assess the association between lifetime use of anticoagulants and prostate cancer risk. RESULTS: 102 subjects (2.6 % of cases and 3.7 % of controls) reported a history of oral anticoagulant therapy. After controlling for age, ancestry, education, family history of prostate cancer, prostate cancer screening frequency, diabetes, body mass index and statin use, ever use of oral anticoagulants showed a weak inverse, non-statistically significant association with prostate cancer (odds ratio 0.76, 95% confidence interval 0.50-1.16). Similar results were observed in analyses considering duration of use or indication for use, restricted to subjects recently screened or stratified by cancer aggressiveness. CONCLUSIONS: Our findings provide weak support for a protective effect of oral anticoagulant therapy against prostate cancer. Further confirmation is required, especially in light of potential bleeding complications associated with anticoagulants.

Cognitive disorders and occupational exposure to organophosphates: results from the PHYTONER study.

The involvement of organophosphate insecticides in cognitive disorders is supported by epidemiologic and biological evidence, but the effects of long-term exposure remain debated. We studied the association between organophosphate exposure and cognitive performance in vine workers from the PHYTONER study cohort in the Bordeaux area of France. Results from interviews of 614 subjects conducted at the 4-year follow-up between 2001 and 2003 were analyzed. Exposure to pesticides since 1950 was assessed with cumulative exposure scores for 34 organophosphates combining an historical crop-exposure pesticide matrix and field exposure studies, taking into account the characteristics of treatment (mixing, spraying, equipment cleaning) and reentry tasks. For the 11 organophosphates retained in the analysis, exposure (ever vs. never) was associated with low cognitive performance. No dose-effect relationship was found, but an increased risk was observed with a 50-mg increase in the cumulative score, which was greater with mevinphos (Benton Visual Retention Test: odds ratio = 3.26, 95% confidence interval: 1.54, 6.88; Trail Making Test, part A: odds ratio = 3.03, 95% confidence interval: 1.39, 6.62). Our results support the hypothesis that cognitive disorders observed in vine workers may be associated with exposure to specific organophosphates.

Levels and determinants of pesticide exposure in operators involved in treatment of vineyards: results of the PESTEXPO Study.

Exposure assessment is a critical point for epidemiological studies on pesticide health effects. PESTEXPO study provides data on levels of exposure and their determinants in real conditions of pesticide use. We described levels of exposure in vineyards during treatment tasks (mixing, spraying and cleaning) and we analysed their determinants. Sixty-seven operators using dithiocarbamates or folpet were observed. Detailed information on the tasks (general conditions, operator, farm and equipment characteristics) were collected and dermal contamination was measured, using patches placed onto the skin on eleven body parts, and washing the hands at the end of each phase. The spraying phase represented roughly half of the contamination, whereas mixing and equipment cleaning accounted for 30% and 20% of the contamination, respectively. The main determinants of exposure were the number of phases, the characteristics of the equipment, the educational level of the operator and his status (farm -worker or -owner) and the general characteristics of the vines. Algorithms were built to estimate daily external contamination, according to these characteristics during mixing, spraying or equipment cleaning. With additional information of frequency and duration of use, they will enable to develop exposure indices usable in epidemiological studies on farmers' health.