2310Universitas MédicaUniv. Méd0041-90952011-0839Pontificia Universidad JaverianaColombiarevistascientificasjaveriana@gmail.com231051147002http://dx.doi.org/10.11144/Javeriana.umed57-4.yearArtículos originales10-Year Experience in Performing Saturation Prostate Biopsy*Diez años de experiencia en la realización de biopsias por saturaciónVillarragaLuis Gabrielluisga.villa@gmail.coRamosJosé Gustavode La HozJoséCataño CatañoJuan GuillermoMD, Departamento de Cirugía, Unidad de Urología, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana Facultad de Medicina, Bogotá, Colombia.Pontificia Universidad JaverianaColombiaMD, Departamento de Cirugía, Unidad de Urología, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana Facultad de Medicina, Bogotá, Colombia.Pontificia Universidad JaverianaColombiaMD. Epidemiologist, Clínica Infantil Colsubsidio, Bogotá, Colombia.Clínica Infantil ColsubsidioColombiaMD-Urology, Departamento de Cirugía, Unidad de Urología, Hospital Universitario San Ignacio-Pontificia Universidad Javeriana, Bogotá, Colombia.Pontificia Universidad JaverianaColombiaHospital Universitario San, Ignacio
Pontifica Universidad Javeriana,
Carrera 7 # 40-62, 8th floor,
Bogotá, Colombia.
luisga.villa@gmail.coOctubre-Diciembre2016574430437130320160305201620062016nohttps://creativecommons.org/licenses/by/4.0/Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.Abstract
Objective: Identify the prostate cancer detection rate in patients in whom underwent a saturation prostate biopsy as a rebiopsy from January 2005 to February 2015 at San Ignacio Hospital. Materials and methods: In San Ignacio hospital were performed from January 2005 to February 2015, 114 saturation biopsies. The investigators made a univariate analysis of the variables. The association between the variable was evaluated based on the T-test and Wilcoxon test. P < 0.05 was considered statistically significant. Finally, a regression model was performed to predict significant variables for prostate cancer. Results: The cancer detection rate using saturation prostate biopsy was 16.7% of which 84% were categorized as significant. A mean of 19 cores were obtained. There were statistically significant differences between patients with prostate cancer and healthy patients in the number of previous biopsies, number of samples, prostate volume and PSA density. Conclusion: Saturation prostate biopsy in our study has a prostate cancer detection rate of 16.7% and 84% of them were significant in this cohort of patients.
Resumen
Objetivo: Identificar la tasa de detección de cáncer de próstata en pacientes en quienes se realizaron biopsias por saturación en el Hospital Universitario San Ignacio desde enero del 2005 hasta febrero del 2015. Métodos: En el Hospital Universitario San Ignacio se han realizado 114 biopsias por saturación. Para este estudio se llevó a cabo un análisis univariado de las variables a estudio. Se obtuvo la asociación por medio del T-test y del test de Wilcoxon con una significancia de 0,05. Por último, se corrió un modelo de regresión para predecir un resultado positivo para cáncer de próstata. Resultados: La tasa de detección de cáncer de próstata fue del 16,7 %, y de estos el 84 % fueron categorizados como significativos. En promedio, se obtuvieron 19 muestras de tejido. El número de biopsias previas, el número de muestras, el volumen de la próstata y la densidad del PSA presentaron valores estadísticamente significativos. Conclusiones: La biopsia por saturación en Colombia presenta una tasa de detección de cáncer de próstata del 16,7 %, de las cuales el 84 % fueron significativas.
Prostate cancer, excluding non-melanoma skin cancer, is the most common cancer among men in the United States [1], and in Colombia it is also the most common cancer, and constitutes the second leading cause of mortality in men, according to the Ministry of Health of Colombia [2].
A positive prostate biopsy it´s required for diagnosing prostate cancer, allowing to stage and define treatment. An accurate biopsy scheme should be select, taking into account patient characteristics and medical history; in order to decrease the number of false negatives.
In the sextant method described by Hodge et al. in 1989, the investigators took cores of the apex, base and middle of the prostate, with a prostate cancer detection rate between 20% and 35% approximately [3]. Because of its low detection rate, an extended biopsy was proposed, which consists in obtaining 5 to 7 cores in each side [4]. Different authors have considered that increasing the number of cores, increases the detection rate; so that above 6 cores, the detection of positive cores increased in 5-30% [5,6,7]. In the extended biopsy scheme, 10 to 12 cores are taken; above this number of cores the concept of saturation biopsy is made, in which it is desired to acquire a greater amount of tissue for histopathological analysis, obtaining around 20 samples [8].
Saturation biopsy is considered as a diagnostic tool in prostate cancer; the 2013 guidelines of the health ministry of Colombia recommend the performance of a saturation biopsy in men with persistently elevated PSA levels and multiple previous negative prostate biopsies [9].
It is important to know the impact that this diagnostic test has in our population, so we can define the utility and the target population. Knowing the detection rate for saturation prostate biopsy in Colombian men, allow us to compare our results with those reported in the literature.
Methods
Type of study: Analytical cross-sectional study.
Study Population: Male who underwent saturation prostate biopsy at the San Ignacio Hospital, from January 2005 to February 2015. Inclusion criteria: patients that were in the INTRANET database and in whom saturation biopsy was performed by the Urology Department. Exclusion criteria: biopsies with less than 16 cores and patients who had already a diagnosis of prostate cancer.
Data collection: Was performed by searching medical records in the electronic database (INTRANET), of the San Ignacio hospital from January 2005 to February 2015, containing as a keyword prostate and biopsy (Performed by the unit of Urology). From this research the investigators obtained 177 medical records, and after applying inclusion and exclusion criteria, 114 medical records were classified for data collection. The principal investigator was in charge of reviewing each of the medical records, and collected the following data: age, saturation biopsy indication, initial PSA, number of previous biopsies, histology of previous biopsies, number of cores obtained in the saturation biopsy, prostate volume, and the histologic result of the saturation biopsies.
Statistical analysis: The investigators made a univariate analysis of the variables. Mean was obtained for the quantitative variables, with their respective standard deviation or range. Frequencies and proportions were obtained for the qualitative variables. The association between the variable were evaluated based on the T-test and Wilcoxon test. P < 0.05 was considered statistically significant. Finally, a regression model was made to predict prostate cancer.
Ethical considerations: The study was approved by the Ethics Committee of the Pontificia Universidad Javeriana and complied with the provisions of the Best Clinical Practice Guidelines, the Declaration of Helsinki, and local regulations. Following the guidelines of the resolution 8430 of 1993 of the Colombian Health Ministry, the following research protocol is classified as a safe investigation under Article 11. Therefore, and in compliance with the first paragraph of Article 16 of the same resolution, it is not required a written informed consent because of the low risk of the investigation.
Funding source: San Ignacio Hospital.
Conflicts of interest: The authors declare that they have no conflict of interest.
Results
We analyzed 114 clinical records, the average age was 61.7 years (SD = 7.1), with a minimum age of 44 and a maximum of 84 years. 55.8% of the patients had an initial PSA greater than 10 mg/dl and 83.5% had two previous biopsies. The principal indications for biopsy were a persistent elevated PSA greater than 4 ng/ml (92%), followed by atypia and multifocal high grade prostatic intraepithelial neoplasia on previous biopsy with a 4.9% and finally a 3% for histology on previous biopsy (atypia and multifocal high grade prostatic intraepithelial neoplasia) and persistent elevated PSA. The mean for cores taken were 19 (SD = 2.75).
The cancer detection rate using saturation prostate biopsy was 16.7% of which 84% were categorized as significant, where the predominant variable for categorization was the PSA density greater than 0.15 ng/ml in 13 patients, followed by the number of positive cores ≥ 3 (10 patients). Of the patients with adenocarcinoma Gleason score was 6 in 61.1%, 7 in 27.7%, and 8 in 11.1%. Age and initial PSA, didn’t have an association with cancer. The number of previous biopsies, number of cores, the prostate volume and the PSA density had a statistically significant association (p<0.05) with prostate cancer (Table 1). In those with adenocarcinoma, the prostate volume was lower (40.78 vs. 50.25) and less cores (18.42 vs. 19.69) were taken.
The PSA density was used to develop a ROC curve (Figure 1), and the area under the curve was 0.63 [95% CI (0.47 to 0.80)]. A logistic regression model was developed using the continuous variables which had a p<0.05 to predict prostate cancer. The investigators found that in this model none of the variables were sufficient as a single predictor for prostate cancer.
ROC Curve PSA density for Prostate Cancer
Figure 1 ROC Curve PSA density for Prostate Cancer
Discussion
According to the Centers for Disease Control and Prevention (CDC) in 2010 the most common cancer in the United States among men was prostate cancer (PC) with 126.1 cases per 100,000 population [10]. In Colombia there are few sources of information about the epidemiology of the disease, however according to the National Cancer Institute [2] in 2006 about 7,957 new cases of PC were estimated for each year, which represents an age-adjusted incidence rate of 47.8 cases per 100,000 men, and leading cause of mortality in 2,379 cases in 2011.
Saturation Biopsy is one of the current diagnostic tools for PC. International guidelines currently recommend performing saturation biopsy in patients with persistently elevated PSA levels, multiple previous negative prostate biopsies, atypical small acinar proliferation of prostate and multifocal high grade prostatic intraepithelial neoplasia, patients in active survey and candidates to focal therapy [8,9,11,12,13,14]. It is estimated that around a 25% of patients with prostate cancer are identified after a negative biopsy [15].
There are controversial issues in performing saturation biopsy such as: the number of cores required and it´s relationship between the cancer detection rate and prostate volume [8]. Our study found that patients with prostate cancer had a lower volume (40.78 ml) and required fewer number of cores (18.42), while patients in whom no cancer was detected, the prostate volume was higher (50.25 cm3) and higher number of cores were taken (19.69); both differences were statistically significant. However, the study couldn’t find out a cutoff to define how many samples are required for prostate cancer detection in relationship with the prostate volume; more studies are required for this type of analysis.
Stewart et al. [16] and Scattoni et al. [7] reported prostate cancer detection rates between 30-34%. In our study the detection rate was 16.7%. This differences are explained by the fact that the populations were different. In the two studies cited above the saturation biopsy was performed in patients who had an initial sextant prostate biopsy, and in our population they had an initial biopsy with an average of 12 cores. By increasing the number of cores, the initial detection rate increased; so that above 6 cores, the detection rate for PC increased in 5-30% [5,6,7].
Another scenario for saturation biopsy is the detection of significant prostate cancer, defined as the one who has an effect on patient mortality and the capacity to develop metastatic disease. Epstein et al [17] in 1994 defined insignificant cancer and these standards still apply, such as: PSA density <0.15 ng/ml, biopsy Gleason ≤6, the presence of cancer in less than 3 samples and the presence of ≤50% commitment of sample. Zaytoun et al. [18], showed a detection rate of significant prostate cancer of 33.3% with saturation biopsy. In our study, the detection rate for significant cancer was 84%. The predominant variable in patients with significant prostate cancer was PSA density, which correlates with the data obtained in Table 1. However, as a diagnostic tool is not useful because of its low area under the curve obtained in the ROC curve.
Data
Table 1 Data
* T-test; + = Wilcoxon test.
Nonetheless, prostate biopsy guided by ultrasound has limitations as false negatives, risk of and incorrect stratification, detection of insignificant prostate cancer and the need of multiple biopsies [19].
Today there are new techniques to offer to these patients, such as the MRI guided biopsy. Its detection rate is between 39-59% [20,21,22,23], with high detection rate in significant cancer [20]. However, MRI-guided biopsy could not be implemented in daily use by the urologist, due to lack of studies [19].
Saturation biopsy is a diagnostic study sustained by international and national guidelines in the study of prostate cancer. Our study showed a high detection rate in significant prostate cancer, and found that variables such as number of previous biopsies, number of cores, prostate volume and density of PSA are associated with prostate cancer detection. A greater number of studies are required in saturation biopsy to define their diagnostic utility.
References 1. Brawley OW. Prostate cancer epidemiology in the United States. World J Urol. 2012;30(2):195-200. Epub 2012/04/06. BrawleyOWProstate cancer epidemiology in the United States2012302195200Epub 2012/04/06 2. Instituto Nacional de Cancerología. Información sobre el cancer [internet]. Instituto Nacional de Cancerologia; 2011 [updated 2011; cited 2014 ene 4]. Disponible en: http://www.cancer.gov.co/contenido/contenido.aspx?catID=434&conID=790 . Instituto Nacional de Cancerología20112014/01/04[internet]Disponible en: http://www.cancer.gov.co/contenido/contenido.aspx?catID=434&conID=790 3. Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol. 1989;142(1):71-4; discussion 4-5. Epub 1989/07/01. HodgeKKMcNealJETerrisMKStameyTARandom systematic versus directed ultrasound guided transrectal core biopsies of the prostate198914217174discussion 4-5Epub 1989/07/01 4. Ukimura O, Coleman JA, de la Taille A, Emberton M, Epstein JI, Freedland SJ, et al. Contemporary role of systematic prostate biopsies: indications, techniques, and implications for patient care. Eur Urol. 2013;63(2):214-30. Epub 2012/10/02. UkimuraOColemanJAde la TailleAEmbertonMEpsteinJIFreedlandSJContemporary role of systematic prostate biopsies: indications, techniques, and implications for patient care2013632214230Epub 2012/10/02 5. Naughton CK, Miller DC, Mager DE, Ornstein DK, Catalona WJ. A prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection. J Urol. 2000;164(2):388-92. Epub 2000/07/14. NaughtonCKMillerDCMagerDEOrnsteinDKCatalonaWJA prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection20001642388392Epub 2000/07/14 6. Siu W, Dunn RL, Shah RB, Wei JT. Use of extended pattern technique for initial prostate biopsy. J Urol. 2005;174(2):505-9. Epub 2005/07/12. SiuWDunnRLShahRBWeiJTUse of extended pattern technique for initial prostate biopsy20051742505509Epub 2005/07/12 7. Scattoni V, Maccagnano C, Zanni G, Angiolilli D, Raber M, Roscigno M, et al. Is extended and saturation biopsy necessary? Int J Urol.. 2010;17(5):432-47. Epub 2010/04/27. ScattoniVMaccagnanoCZanniGAngiolilliDRaberMRoscignoMProstate saturation biopsy following a first negative biopsy: state of the art2010175432447Epub 2010/04/27 8. Maccagnano C, Gallina A, Roscigno M, Raber M, Capitanio U, Sacca A, et al. Prostate saturation biopsy following a first negative biopsy: state of the art. Urol Int. 2012;89(2):126-35. Epub 2012/07/21. MaccagnanoCGallinaARoscignoMRaberMCapitanioUSaccaAProstate saturation biopsy following a first negative biopsy: state of the art2012892126135Epub 2012/07/21 9. Instituto Nacional de Cancerología, Sociedad Colombiana de Urología. Guía de práctica clínica (GPC) para la detección temprana, diagnóstico, tratamiento integral, seguimiento y rehabilitación de pacientes con diagnóstico de cáncer de próstata para el Sistema General de Seguridad Social en Salud, Colombia [internet]. Bogotá: Ministerio de Salud y Protección Social-Departamento Administrativo de Ciencia Tecnología e Innovación en Salud (Colciencias); 2013. Disponible en: https://docs.supersalud.gov.co/PortalWeb/Comunicaciones/GuiasPracticasClinica/guia015-2013-cancer-de-prostata-01-08-13.pdf Instituto Nacional de CancerologíaSociedad Colombiana de Urología2013BogotáMinisterio de Salud y Protección Social-Departamento Administrativo de Ciencia Tecnología e Innovación en Salud (Colciencias)[internet]Disponible en: https://docs.supersalud.gov.co/PortalWeb/Comunicaciones/GuiasPracticasClinica/guia015-2013-cancer-de-prostata-01-08-13.pdf 10. Centers for Disease Control and Prevention. Cancer among men [internet]; 2013 [citado 2014 ene 4]. Disponible en: http://www.cdc.gov/cancer/dcpc/data/men.htm . Centers for Disease Control and Prevention20132014/01/04[internet]Disponible en: http://www.cdc.gov/cancer/dcpc/data/men.htm 11. Carroll PR, Parsons JK, Andriole G, Bahnson RR, Barocas DA, Catalona WJ, et al. Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2014;12(9):1211-9; quiz 9. Epub 2014/09/06.CarrollPRParsonsJKAndrioleGBahnsonRRBarocasDACatalonaWJProstate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines201412912111219quiz 9Epub 2014/09/06 12. Mottet N, Bastian P, Bellmunt J, van den Bergh R, Bolla M, van Casteren N, et al. Guidelines on prostate cancer. Eur Urol. 2014;65(1):124-37. MottetNBastianPBellmuntJvan den BerghRBollaMvan CasterenNGuidelines on prostate cancer2014651124137 13. Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, et al. Prostate specific antigen best practice statement: 2009 update. J Urol. 2013;189(1 Suppl):S2-S11. Epub 2012/12/19. GreeneKLAlbertsenPCBabaianRJCarterHBGannPHHanMProstate specific antigen best practice statement2009189211Epub 2012/12/191 14. Djavan B, Ravery V, Zlotta A, Dobronski P, Dobrovits M, Fakhari M, et al. Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J Urol. 2001;166(5):1679-83. Epub 2001/10/05. DjavanBRaveryVZlottaADobronskiPDobrovitsMFakhariMProspective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop?2001166516791683Epub 2001/10/05 15. Roehl KA, Antenor JA, Catalona WJ. Serial biopsy results in prostate cancer screening study. J Urol. 2002;167(6):2435-9. Epub 2002/05/07. RoehlKAAntenorJACatalonaWJSerial biopsy results in prostate cancer screening study2002167624352439Epub 2002/05/07 16. Stewart CS, Leibovich BC, Weaver AL, Lieber MM. Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol. 2001;166(1):86-91; discussion -2. Epub 2001/07/04.StewartCSLeibovichBCWeaverALLieberMMProstate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies200116618691discussion-2Epub 2001/07/04 17. Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994;271(5):368-74. Epub 1994/02/02.EpsteinJIWalshPCCarmichaelMBrendlerCBPathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer19942715368374Epub 1994/02/02 18. Zaytoun OM, Moussa AS, Gao T, Fareed K, Jones JS. Office based transrectal saturation biopsy improves prostate cancer detection compared to extended biopsy in the repeat biopsy population. J Urol. 2011;186(3):850-4. Epub 2011/07/27.ZaytounOMMoussaASGaoTFareedKJonesJSOffice based transrectal saturation biopsy improves prostate cancer detection compared to extended biopsy in the repeat biopsy population20111863850854Epub 2011/07/27 19. Bjurlin MA, Meng X, Le Nobin J, Wysock JS, Lepor H, Rosenkrantz AB, et al. Optimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment. J Urol. 2014;192(3):648-58. Epub 2014/04/29. BjurlinMAMengXLe NobinJWysockJSLeporHRosenkrantzABOptimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment20141923648658Epub 2014/04/29 20. Hoeks CM, Schouten MG, Bomers JG, Hoogendoorn SP, Hulsbergen-van de Kaa CA, Hambrock T, et al. Three-Tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers. Eur Urol. 2012;62(5):902-9. Epub 2012/02/14.HoeksCMSchoutenMGBomersJGHoogendoornSPHulsbergen-van de KaaCAHambrockTThree-Tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers2012625902909Epub 2012/02/14 21. Franiel T, Stephan C, Erbersdobler A, Dietz E, Maxeiner A, Hell N, et al. Areas suspicious for prostate cancer: MR-guided biopsy in patients with at least one transrectal US-guided biopsy with a negative finding--multiparametric MR imaging for detection and biopsy planning. Radiology. 2011;259(1):162-72. Epub 2011/01/15.FranielTStephanCErbersdoblerADietzEMaxeinerAHellNAreas suspicious for prostate cancer: MR-guided biopsy in patients with at least one transrectal US-guided biopsy with a negative finding--multiparametric MR imaging for detection and biopsy planning20112591162172Epub 2011/01/15 22. Sciarra A, Panebianco V, Ciccariello M, Salciccia S, Cattarino S, Lisi D, et al. Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin Cancer Res.. 2010;16(6):1875-83. Epub 2010/03/04.SciarraAPanebiancoVCiccarielloMSalcicciaSCattarinoSLisiDValue of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy201016618751883Epub 2010/03/04 23. Anastasiadis AG, Lichy MP, Nagele U, Kuczyk MA, Merseburger AS, Hennenlotter J, et al. MRI-guided biopsy of the prostate increases diagnostic performance in men with elevated or increasing PSA levels after previous negative TRUS biopsies. Eur Urol. 2006;50(4):738-48; discussion 48-9. Epub 2006/04/25. AnastasiadisAGLichyMPNageleUKuczykMAMerseburgerASHennenlotterJ2006504738748discussion 48-9Epub 2006/04/25Notes
This article was supported by Hospital Universitario San Ignacio.