ANTICANCER RESEARCH 35: 2881-2886 (2015)
Development and Validation of a Nomogram to Estimate the Risk of Prostate Cancer in Brazil THIAGO B. SILVA1, CLEYTON Z. OLIVEIRA2, ELINEY F. FARIA3, EDMUNDO C. MAUAD1, KARI J. SYRJÄNEN2,4 and ANDRÉ L. CARVALHO2
Departments of 1Cancer Prevention and 3Surgery/Urology, Barretos Cancer Hospital, Barretos, SP, Brazil; 2Teaching and Research Institute, Barretos Cancer Hospital, Barretos, SP, Brazil; 4Department of Clinical Research, Biohit HealthCare Plc., Helsinki, Finland
Abstract. Aim: To develop and validate a nomogram to estimate the probability of prostate cancer (PCa) in men undergoing opportunistic screening. Patients and Methods: This was a cross-sectional observational study on a cohort of men screened for PCa at the Barretos Cancer Hospital (BCH) between January 2004 and December 2007. Patients’ data were collected from their charts and binary logistic regression analyses were performed to assess the power of various factor combinations as predictors of the PCa risk. Results: Out of the 1,313 screened men who underwent prostate biopsy, 553 (42.1%) had histopathological confirmation of PCa. The logistic regression analyses provided an area under the receiver operating characteristics (ROC) curve (AUC) of 0.737 (95% confidence interval (CI)=0.678-0.796) for the best predictor combination. A nomogram was constructed to estimate the individual risk for PCa prior to biopsy. Conclusion: Our nomogram provides an easy and practical method, superior in performance to the traditional criteria, predicting the diagnosis of PCa with a reasonable accuracy. Prostate cancer (PCa) is a major cause of morbidity and cancer mortality worldwide (1). In the US, 241,740 new cases of PCa were diagnosed resulting in 28,170 deaths in 2012 (2). In Europe, PCa is the most common cancer among males and the third leading cause of cancer-related deaths (3). Of the 382,000 cases (22% of all cancers in men)
This article is freely accessible online. Correspondence to: Thiago Buosi Silva, Ph.D., Barretos Cancer Hospital, Rua Antenor, Duarte Villella, 1331-Bairro Dr. Paulo Prata, 14784-400, Barretos, SP, Brazil, Tel/Fax: +55 1733216600/1733216789, e-mail:
[email protected] Key Words: Biopsy, predictive value, prostate neoplasms, model, nomogram, screening programs.
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diagnosed in Europe in 2008, 89,000 (9.3%) patients died of cancer progression (3). PCa remains to be the most common neoplasm in the male population of Brazil and the second leading cause of cancer-related death. According to the Brazilian National Cancer Institute, there were 60,180 new cases of PCa in 2012 translating to an incidence of 62/100,000 (4). The global incidence of PCa has increased significantly since 1990, mainly due to the implementation of cancer screening programs, e.g. by prostate-specific antigen (PSA) test and digital rectal examination (DRE) (5). However, the effectiveness of PSA testing and DRE remains controversial. Many experts argue that current data are insufficient to prove that these methods bring more benefits than risks (2). It is undisputed, however, that screening for PCa leads to early diagnosis, possibly resulting in decreased mortality. However, screening may also increase the burden of many patients who do not benefit from the treatment and screening (6). While the definitive diagnosis of PCa is performed by core needle biopsy, this costly and invasive procedure could be preferably avoided (7). The use of alternative tools with high accuracy in predicting the presence of cancer, such as a nomogram, might help reduce the number of unnecessary biopsies, pain and morbidity in men (8). A nomogram is a device or model using an algorithm or mathematical formula composed of several variables predicting the probability of an event or outcome (9), such as the occurrence of cancer in prostate biopsy. These models are designed to quantify the combination of several risk factors capable of probabilistic prediction of the outcome of interest. In this context, nomograms can improve the efficiency of PCa detection, exceeding the performance of even the experienced clinical experts (10). The aim of the present study was to develop and validate nomograms for estimation of the probability of cancer in patients undergoing opportunistic PCa screening in Brazil.
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ANTICANCER RESEARCH 35: 2881-2886 (2015) Table I. Socio-demographic characteristics and the clinical, radiological and laboratory results of the men subjected to prostate biopsy.
Table II. Area under the receiver operating characteristics (ROC) curve (AUC) for the predictors of prostate cancer risk individually.
Variable
Model
Category
n
%
Illiterate Basic education (complete) Basis education (incomplete) High school Higher education
294 847 101 42 24
22.4 64.5 7.7 3.3 1.8
State
Goiás Minas Gerais Mato Grosso do Sul Mato Grosso Rondônia São Paulo
49 101 184 91 49 839
3.7 7.7 14.0 6.9 3.7 63.9
DRE
Normal Changed
599 714
45.6 54.4
0 to 2.49 2.5 to 3.99 4.0 to 9.99 ≥10
113 227 687 286
8.6 17.3 52.3 21.8
0 to 10.0 10.1 to 15.0 15.1 to 20.0 ≥20.1 Not measured
1,062 26 30 37 158
80.9 2.0 2.3 2.8 12.0
0 to 0.09 0.10 to 0.149 0.15 to 0.199 ≥0.20
426 349 182 352
32.5 26.7 13.9 26.9
Education*
PSA (ng/ml)
%fPSA (%)
PSA density§ (ng/ml.cm3)
DRE, Digital rectal examination of the prostate; PSA, prostate-specific antigen; %fPSA, ratio of the free PSA/total PSA; Basic education equals to the education of elementary school/middle school. *Five cases with no data. §Four cases with no data
Patients and Methods This is an observational study of a cross-sectional cohort of men who underwent Mobile Cancer Prevention Unit (MCPU) cancer screenings conducted by the Department of Prevention, Barretos Cancer Hospital (BCH) between January 2004 and December 2007. The details of the MCPU cancer screening program have been previously described (11). The age range of the men varied between 45 and 80 years with a definitive indication for biopsy: PSA≥4 ng/ml and/or a DRE suspect for PCa and/or PSA≥2.5 ng/ml with a free/total PSA ratio (%fPSA) ≤15%. All eligible men were referred to the Department of Prevention, HCB, for further evaluation. An ultrasound-guided prostate biopsy using an 18-gauge needle was performed and 6-16 fragments were submitted for histological examination (median of 12 fragments). The data for constructing the models were collected from the patient charts, including the family history of PCa, education level,
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Positive for PCa (n)
Education Family history Age Total PSA %fPSA Ultrasound PSA density DRE
411 553 553 553 482 553 551 553
Negative Area under for PCa (n) the curve
570 759 760 760 673 759 758 760
0.507 0.505 0.567 0.646 0.283 0.585 0.736 0.496
95% Confidence Intervals Lower
Upper
0.471 0.474 0.536 0.615 0.253 0.554 0.709 0.465
0.544 0.537 0.598 0.676 0.312 0.616 0.764 0.528
PCa, Prostate cancer; %fPSA, ratio of the free PSA/total PSA; DRE, digital rectal examination of the prostate; PSA, prostate-specific antigen.
age, results of DRE, PSA values and %fPSA. The radiological data available in this study consisted of prostate volume and ultrasound results. Finally, the pathological data comprised of biopsy results. Latent cancer was defined as a tumor with the total tumor volume
