Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis Cosimo De Nunzio, Fabrizio Presicce, Riccardo Lombardo, Fabiana Cancrini, Stefano Petta, Alberto Trucchi, Mauro Gacci*, Luca Cindolo† and Andrea Tubaro Department of Urology, Sant’ Andrea Hospital, ‘La Sapienza’ University of Rome, Rome, *Department of Urology, Careggi Hospital, University of Florence, Florence, and †Department of Urology, Padre Pio Hospital, Vasto, Italy
Objectives To assess the association between physical activity, evaluated by the Physical Activity Scale for the Elderly (PASE) questionnaire, and prostate cancer risk in a consecutive series of men undergoing prostate biopsy.
Patients and Method From 2011 onwards, consecutive men undergoing 12-core prostate biopsy were enrolled into a prospective database. Indications for a prostatic biopsy were a prostate-specific antigen (PSA) value of ≥4 ng/mL and/or a positive digital rectal examination. Body mass index (BMI) and waist circumferences were measured before the biopsy. Fasting blood samples were collected before biopsy and tested for: total PSA, glucose, high-density lipoprotein cholesterol, and trygliceride levels. Blood pressure was recorded. Metabolic syndrome (MetS) was defined according to the Adult Treatment panel III. The PASE questionnaire was completed before the biopsy.
Results In all, 286 patients were enrolled with a median (interquartile range, IQR) age and PSA level of 68 (62–74) years and 6.1 (5–8.8) ng/mL, respectively. The
Introduction Prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer deaths in Western countries [1,2]. Race, family history and age are the only established risk factors associated with prostate cancer development. However, the large geographic variation in prostate cancer risk suggests that lifestyle factors, such as physical activity and a higher intake of dietary fat and meat, may play a significant role in the pathogenesis and prognosis of cancer and particularly prostate cancer [2]. Recent evidence suggests that in men with a previous prostate cancer
© 2015 The Authors BJU International © 2015 BJU International | doi:10.1111/bju.13157 Published by John Wiley & Sons Ltd. www.bjui.org
median (IQR) BMI was 26.4 (24.6–29) kg/m2 and waist circumference was 102 (97–108) cm, with 75 patients (26%) presenting with MetS. In all, 106 patients (37%) had prostate cancer at biopsy. Patients with prostate cancer had higher PSA levels (median [IQR] 6.7 [5–10] vs 5.6 [4.8– 8] ng/mL; P = 0.007) and lower LogPASE scores (median [IQR] 2.03 [1.82–2.18] vs 2.10 [1.92–2.29]; P = 0.005). On multivariate analysis, in addition to well-recognised risk factors such as age, PSA level and prostate volume, LogPASE score was an independent risk factor for prostate cancer diagnosis (odds ratio [OR] 0.146, 95% confidence interval [CI] 0.037–0.577; P = 0.006]. LogPASE score was also an independent predictor of high-grade cancer (OR 0.07, 95% CI 0.006–0.764; P = 0.029).
Conclusion In our single-centre study, increased physical activity, evaluated by the PASE questionnaire, is associated with a reduced risk of prostate cancer and of high-grade prostate cancer at biopsy. Further studies should clarify the molecular pathways behind this association.
Keywords prostate cancer, physical activity, needle biopsy, prostate
diagnosis, physical activity is associated with lower overall mortality and prostate cancer-specific mortality [3,4]. A modest amount of vigorous activity for ≥3 h/week may also substantially improve prostate cancer-specific survival [3]. However, all these experiences should be considered preliminary and further studies are needed to address the possible effect of physical activity and lifestyle interventions on prostate cancer diagnosis and treatment [5]. Furthermore, epidemiological data on the association between physical activity status and new onset prostate cancer are inconclusive and controversial results have been obtained in different settings [6–10]. The most important differences seem in these
BJU Int 2016; 117: E29–E35 wileyonlinelibrary.com
De Nunzio et al.
studies are related to difficulties in evaluating type, frequency, duration and intensity of physical activity, as well as limited data available for prostate cancer stage and grade [6–11]. Furthermore, in previous studies prostate cancer incidence was ascertained from medical records and/or state cancer registries [8,9,11]. To date, to our knowledge, only one study has examined the association between exercise and prostate cancer in North American patients undergoing prostate biopsy [12]. Considering this, we designed the first study in Europe to evaluate the association between physical activity, assessed with a validated questionnaire, and prostate cancer risk in a consecutive series of men undergoing prostate biopsy.
Patients and Methods From January 2010, patients referred to our prostate clinic with a PSA level of ≥4 ng/mL or an abnormal DRE were scheduled for TRUS-guided prostate biopsy after signing an informed consent and following internal Ethical Board Committee approval of the study protocol. All the research activities were consistent with the Human Subjects Protection Statements and the study can be classified as a G3A. We excluded from the study patients who had a history of prostate cancer or prostate surgery, and patients on finasteride or dutasteride. Prostate biopsies were taken as an outpatient procedure. All patients underwent 12-core TRUSguided biopsy using Falcon ultrasound equipment (B-K Medical, Milan, Italy) equipped with a 5–10 MHz bi-convex probe (8808 probe B-K Medical). We used a 16-G biopsy needle (Magnum 1000; BARD, Rome, Italy) and a dedicated spring-loaded biopsy gun (MG1522; BARD). Antibiotic prophylaxis and periprostatic anaesthetic block was used according to our Departmental protocol [13]. High-grade disease was defined as a biopsy Gleason score of ≥7. A single pathologist, ‘blinded’ to the clinical data except for patient age, was assessed the biopsies. Assessments of Metabolic Status and Physical Activity Before the biopsy procedure, patients underwent a detailed physical examination, including height, weight and waist circumference measurement. Body mass index (BMI) was calculated as weight in kilogrammes divided by height in metres, squared (kg/m2). Obesity was defined as a BMI of ≥30 kg/m2 according to the WHO definition applicable to the European population [14].The waist circumference was measured, using a standard measurement strip with the patients standing and breathing normally, at the midway between the lowest rib margin and iliac crest. Additionally, resting blood pressure was recorded as the first and fifth Korotkof sounds by auscultatory methods. Finally, fasting
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© 2015 The Authors BJU International © 2015 BJU International
(8 h) blood samples were drawn from all patients 2 h before biopsy. Serum samples were analysed for blood glucose, high-density lipoprotein (HDL) cholesterol, triglycerides and total PSA. The data were used to define a binary variable for the presence or absence of the metabolic syndrome (MetS) according to the criteria proposed by the Adult Treatment panel III [15]. Patients with three or more of the following factors were classified as having the MetS: waist circumference >102 cm; triglycerides ≥150 mg/dL; HDL
Objectives To assess the association between physical activity, evaluated by the Physical Activity Scale for the Elderly (PASE) questionnaire, and prostate cancer risk in a consecutive series of men undergoing prostate biopsy.
Patients and Method From 2011 onwards, consecutive men undergoing 12-core prostate biopsy were enrolled into a prospective database. Indications for a prostatic biopsy were a prostate-specific antigen (PSA) value of ≥4 ng/mL and/or a positive digital rectal examination. Body mass index (BMI) and waist circumferences were measured before the biopsy. Fasting blood samples were collected before biopsy and tested for: total PSA, glucose, high-density lipoprotein cholesterol, and trygliceride levels. Blood pressure was recorded. Metabolic syndrome (MetS) was defined according to the Adult Treatment panel III. The PASE questionnaire was completed before the biopsy.
Results In all, 286 patients were enrolled with a median (interquartile range, IQR) age and PSA level of 68 (62–74) years and 6.1 (5–8.8) ng/mL, respectively. The
Introduction Prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer deaths in Western countries [1,2]. Race, family history and age are the only established risk factors associated with prostate cancer development. However, the large geographic variation in prostate cancer risk suggests that lifestyle factors, such as physical activity and a higher intake of dietary fat and meat, may play a significant role in the pathogenesis and prognosis of cancer and particularly prostate cancer [2]. Recent evidence suggests that in men with a previous prostate cancer
© 2015 The Authors BJU International © 2015 BJU International | doi:10.1111/bju.13157 Published by John Wiley & Sons Ltd. www.bjui.org
median (IQR) BMI was 26.4 (24.6–29) kg/m2 and waist circumference was 102 (97–108) cm, with 75 patients (26%) presenting with MetS. In all, 106 patients (37%) had prostate cancer at biopsy. Patients with prostate cancer had higher PSA levels (median [IQR] 6.7 [5–10] vs 5.6 [4.8– 8] ng/mL; P = 0.007) and lower LogPASE scores (median [IQR] 2.03 [1.82–2.18] vs 2.10 [1.92–2.29]; P = 0.005). On multivariate analysis, in addition to well-recognised risk factors such as age, PSA level and prostate volume, LogPASE score was an independent risk factor for prostate cancer diagnosis (odds ratio [OR] 0.146, 95% confidence interval [CI] 0.037–0.577; P = 0.006]. LogPASE score was also an independent predictor of high-grade cancer (OR 0.07, 95% CI 0.006–0.764; P = 0.029).
Conclusion In our single-centre study, increased physical activity, evaluated by the PASE questionnaire, is associated with a reduced risk of prostate cancer and of high-grade prostate cancer at biopsy. Further studies should clarify the molecular pathways behind this association.
Keywords prostate cancer, physical activity, needle biopsy, prostate
diagnosis, physical activity is associated with lower overall mortality and prostate cancer-specific mortality [3,4]. A modest amount of vigorous activity for ≥3 h/week may also substantially improve prostate cancer-specific survival [3]. However, all these experiences should be considered preliminary and further studies are needed to address the possible effect of physical activity and lifestyle interventions on prostate cancer diagnosis and treatment [5]. Furthermore, epidemiological data on the association between physical activity status and new onset prostate cancer are inconclusive and controversial results have been obtained in different settings [6–10]. The most important differences seem in these
BJU Int 2016; 117: E29–E35 wileyonlinelibrary.com
De Nunzio et al.
studies are related to difficulties in evaluating type, frequency, duration and intensity of physical activity, as well as limited data available for prostate cancer stage and grade [6–11]. Furthermore, in previous studies prostate cancer incidence was ascertained from medical records and/or state cancer registries [8,9,11]. To date, to our knowledge, only one study has examined the association between exercise and prostate cancer in North American patients undergoing prostate biopsy [12]. Considering this, we designed the first study in Europe to evaluate the association between physical activity, assessed with a validated questionnaire, and prostate cancer risk in a consecutive series of men undergoing prostate biopsy.
Patients and Methods From January 2010, patients referred to our prostate clinic with a PSA level of ≥4 ng/mL or an abnormal DRE were scheduled for TRUS-guided prostate biopsy after signing an informed consent and following internal Ethical Board Committee approval of the study protocol. All the research activities were consistent with the Human Subjects Protection Statements and the study can be classified as a G3A. We excluded from the study patients who had a history of prostate cancer or prostate surgery, and patients on finasteride or dutasteride. Prostate biopsies were taken as an outpatient procedure. All patients underwent 12-core TRUSguided biopsy using Falcon ultrasound equipment (B-K Medical, Milan, Italy) equipped with a 5–10 MHz bi-convex probe (8808 probe B-K Medical). We used a 16-G biopsy needle (Magnum 1000; BARD, Rome, Italy) and a dedicated spring-loaded biopsy gun (MG1522; BARD). Antibiotic prophylaxis and periprostatic anaesthetic block was used according to our Departmental protocol [13]. High-grade disease was defined as a biopsy Gleason score of ≥7. A single pathologist, ‘blinded’ to the clinical data except for patient age, was assessed the biopsies. Assessments of Metabolic Status and Physical Activity Before the biopsy procedure, patients underwent a detailed physical examination, including height, weight and waist circumference measurement. Body mass index (BMI) was calculated as weight in kilogrammes divided by height in metres, squared (kg/m2). Obesity was defined as a BMI of ≥30 kg/m2 according to the WHO definition applicable to the European population [14].The waist circumference was measured, using a standard measurement strip with the patients standing and breathing normally, at the midway between the lowest rib margin and iliac crest. Additionally, resting blood pressure was recorded as the first and fifth Korotkof sounds by auscultatory methods. Finally, fasting
E30
© 2015 The Authors BJU International © 2015 BJU International
(8 h) blood samples were drawn from all patients 2 h before biopsy. Serum samples were analysed for blood glucose, high-density lipoprotein (HDL) cholesterol, triglycerides and total PSA. The data were used to define a binary variable for the presence or absence of the metabolic syndrome (MetS) according to the criteria proposed by the Adult Treatment panel III [15]. Patients with three or more of the following factors were classified as having the MetS: waist circumference >102 cm; triglycerides ≥150 mg/dL; HDL
