A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

Prostate Cancer Clinical Trial

Official title:

A Randomized Controlled Trial To Assess and Compare the Outcomes of 20-core Versus 12-core Prostate Biopsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02825225
• Other study ID #: Prostate biopsy - 01
• Status: Completed
• Phase: N/A
• First received: June 26, 2016
• Last updated: July 3, 2016
• Start date: May 2012
• Est. completion date: June 2016

Study information

• Verified date: July 2016
• Source: University of Nove de Julho
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

The main purpose is to compare the detection rate of 20-core versus 12-core prostate biopsy. The secondary objective is to evaluate pain perception using a validated scale to compare the analgesia provided by the two different local anesthesia schemes. Data will be prospectively collected from patients who will undergo prostate biopsy in a single high volume urology center. The patients will be randomized to two different biopsy samplings and two local anesthesia schemes.

Description:

Prostate cancer is male's leading solid non-cutaneous tumor, and the second cause of cancer death in western countries. The main risk factors are age (5th decade or more), family history and life-style (low physical activity and occidental dietary habit). Due to it's high incidence and mortality, the screening protocols continue to be supported worldwide by the urologic and oncologic societies. The diagnosis of this disease needs histological evidence that is obtained by prostate biopsy which is indicated when prostate specific antigen (PSA) serum levels are elevated or there is suspicion at digital rectal examination. Actual estimations conclude that more than 200.000 new cases are diagnosed per-year in US and much more patients are submitted to biopsies; turning prostate biopsy a routine medical procedure. In therms of current medical evidence there is controversy in some biopsy aspects. The ideal number of fragments to be obtained is not well established. While twelve core is believed to be the minimum to be sampled, the maximum number is not clear. To ease the estimation of the number of necessary core at biopsy the literature recommend the use of nomograms; they adequate the number of removed fragments according to each individual characteristics such as age, volume, previous biopsy and PSA levels. The prostate biopsy is considered a painful procedure by 96% of patients, therefore it is fundamental to soften the soreness employing some form of anesthesia. There is no consensus regarding the ideal protocol but the local anesthesia with the periprostatic blockade is the most employed worldwide. However there is a controversy related to the site of the injection during the periprostatic block in terms of efficacy: base versus apex or both sites.

Considering the epidemiological importance of prostate cancer detection in a continuous aging population, this study protocol was enrolled in a single center high volume urology Brazilian Public Hospital. The patients will be randomized at a 1:1 ratio for the two biopsy schemes and for the two anesthesia templates.The main objective was to compare the detection rate of two different prostate biopsy schemes 20-core versus 12-core prostate biopsy guided by transrectal ultrasound. Secondary objectives were to evaluate pain perception of the two local anesthesia schemes using a validated pain scale. The pain was evaluated using the visual pain scale immediately after the biopsy and one hour after the procedure. The patients were contacted by phone one week after the biopsy to assess the occurrence of any complication. The investigators then compared the major and minor complication rates of 20-core versus 12-core protocol using the Clavien-Dindo scale. In those patients with cancer at the pathologic report that underwent radical prostatectomy, the investigators will also compare the concordance of Gleason score between the biopsy versus surgical specimen according to the biopsy scheme 20-core versus 12-core.

Data was collected since mid 2012 up to june 2016, inclusion and exclusion criteria will be detailed elsewhere. All information was obtained by the main investigator and all procedures were supervised by the main investigator as well.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 750
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• Formal indication to prostate biopsy: PSA elevation, positive digital rectal examination of prostate, prostate cancer active surveillance protocols.

• Patients signing the consent therm agreeing to participate in the trial

• Exclusive local anesthesia prostate biopsy.

• Exclusive transrectal ultrasound guided prostate biopsy.

Exclusion Criteria:

• Transperineal ultrasound guided prostate biopsy

• Magnetic resonance cognitive fusion biopsy.

• Previous treatment with radiation therapy or brachytherapy.

• Previous treatment with focal therapy

• Previous androgen deprivation therapy

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Biopsy/Methods
• Humans
• Image-guided Biopsy/Methods
• Local Anesthesia
• Male
• Prospective Studies
• Prostate Cancer
• Prostate-Specific Antigen/Blood
• Prostate/Pathology
• Prostatic Neoplasms
• Prostatic Neoplasms/Diagnosis
• Ultrasonography, Interventional/Methods

Intervention

Other:
• 20 core-biopsy fragments
Using the extended sextant fashion prostate biopsy, this randomized group was submitted to a 20-fragments core-biopsy to evaluate the diagnostic power, pain perception and complications comparative to institution's standard 12 cores.

Procedure:
• Base and apex local anesthesia
Using the institution's standard local anesthesia protocol (base injection) as active comparator group, this randomized group was submitted to base and apex local anesthetic application to evaluate tolerability of the procedure, pain perception (with use of previous validated analogue pain scale) and complications.

Locations

Country	Name	City	State
Brazil	Hospital Brigadeiro UGA V-SP	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Nove de Julho	Hospital Brigadeiro UGA V-SP

Country where clinical trial is conducted

Brazil, 

References & Publications (20)

Crawford ED. Epidemiology of prostate cancer. Urology. 2003 Dec 22;62(6 Suppl 1):3-12. Review. — View Citation

Descazeaud A, Rubin M, Chemama S, Larré S, Salomon L, Allory Y, Vordos D, Hoznek A, Yiou R, Chopin D, Abbou C, de la Taille A. Saturation biopsy protocol enhances prediction of pT3 and surgical margin status on prostatectomy specimen. World J Urol. 2006 D — View Citation

Giovannucci E, Liu Y, Platz EA, Stampfer MJ, Willett WC. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int J Cancer. 2007 Oct 1;121(7):1571-8. — View Citation

King CR, McNeal JE, Gill H, Presti JC Jr. Extended prostate biopsy scheme improves reliability of Gleason grading: implications for radiotherapy patients. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):386-91. — View Citation

Leite KR, Sousa-Canavez JM, Reis ST, Tomiyama AH, Camara-Lopes LH, Sañudo A, Antunes AA, Srougi M. Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis. Urol Oncol. 2011 May-Jun;29(3):265-9. doi: — View Citation

Leite KR, Tomiyama A, Reis ST, Sousa-Canavez JM, Sañudo A, Dall'Oglio MF, Camara-Lopes LH, Srougi M. MicroRNA-100 expression is independently related to biochemical recurrence of prostate cancer. J Urol. 2011 Mar;185(3):1118-22. doi: 10.1016/j.juro.2010.1 — View Citation

Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SM, Cancio AT, Desaulniers M, Ellis WJ, Rittenhouse H, Groskopf J. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology. 2007 Mar;69(3):532-5. — View Citation

Nash PA, Bruce JE, Indudhara R, Shinohara K. Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol. 1996 Feb;155(2):607-9. — View Citation

Pepe P, Aragona F. Saturation prostate needle biopsy and prostate cancer detection at initial and repeat evaluation. Urology. 2007 Dec;70(6):1131-5. — View Citation

Remzi M, Fong YK, Dobrovits M, Anagnostou T, Seitz C, Waldert M, Harik M, Marihart S, Marberger M, Djavan B. The Vienna nomogram: validation of a novel biopsy strategy defining the optimal number of cores based on patient age and total prostate volume. J — View Citation

Rodríguez-Covarrubias F, González-Ramírez A, Aguilar-Davidov B, Castillejos-Molina R, Sotomayor M, Feria-Bernal G. Extended sampling at first biopsy improves cancer detection rate: results of a prospective, randomized trial comparing 12 versus 18-core pro — View Citation

Ross AE, Loeb S, Landis P, Partin AW, Epstein JI, Kettermann A, Feng Z, Carter HB, Walsh PC. Prostate-specific antigen kinetics during follow-up are an unreliable trigger for intervention in a prostate cancer surveillance program. J Clin Oncol. 2010 Jun 1 — View Citation

Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Páez A, Määttänen L, Bangma CH, Aus G, Carlsson S, Villers A, Rebillard X, van der Kwast T, Kujala PM, Blijenberg BG, Stenman — View Citation

Sfakianos JP, Thorner DA, Dovirak O, Weiss JP, Karanikolas NT. Optimizing prostate cancer detection during biopsy by standardizing the amount of tissue examined per core. BJU Int. 2011 Nov;108(10):1578-81. doi: 10.1111/j.1464-410X.2011.10239.x. Epub 2011 — View Citation

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 201 — View Citation

Sonn GA, Natarajan S, Margolis DJ, MacAiran M, Lieu P, Huang J, Dorey FJ, Marks LS. Targeted biopsy in the detection of prostate cancer using an office based magnetic resonance ultrasound fusion device. J Urol. 2013 Jan;189(1):86-91. doi: 10.1016/j.juro.2 — View Citation

Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. The influence of finasteride on the development of prostate cancer. N Engl J Med. — View Citation

Ukimura O, Coleman JA, de la Taille A, Emberton M, Epstein JI, Freedland SJ, Giannarini G, Kibel AS, Montironi R, Ploussard G, Roobol MJ, Scattoni V, Jones JS. Contemporary role of systematic prostate biopsies: indications, techniques, and implications fo — View Citation

Zaytoun OM, Jones JS. Prostate cancer detection after a negative prostate biopsy: lessons learnt in the Cleveland Clinic experience. Int J Urol. 2011 Aug;18(8):557-68. doi: 10.1111/j.1442-2042.2011.02798.x. Epub 2011 Jun 21. Review. — View Citation

Zisman A, Leibovici D, Kleinmann J, Siegel YI, Lindner A. The impact of prostate biopsy on patient well-being: a prospective study of pain, anxiety and erectile dysfunction. J Urol. 2001 Feb;165(2):445-54. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with prostate cancer detected.	Statistical evaluation comparing detection of prostate cancer in 12-core versus 20 cores.	Through study completion, an average of four years.	No
Secondary	Number of participants with complications	Comparison of data between 12 versus 20 core-biopsy and base versus base plus apex anesthesia in therms of complication occurrence.	Immediate, early (30 minutes) and late (within first week)	No
Secondary	Core biopsy accuracy.	Comparison of cancer positive pathology data between 12 and 20 core-biopsy with their respective radical prostatectomy hole mount pathology specimen (when treatment was indicated).	Through study completion, at time of surgery.	No
Secondary	Pain perception using pain analogue scale.	Compare pain perception of two anesthesia scheme base versus base plus apex using the visual pain analogue scale immediately after the biopsy and 30 minutes later. The investigators will also compared the analgesia of these schemes according to PSA, PSA density, free/total PSA ratio, prostate volume, previous biopsy.	Immediate and early (30 minutes after biopsy).	No
Secondary	Number of participants with prostate cancer detected according to PSA value	The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to the PSA value.	Through study completion, an average of four years.	No
Secondary	Number of participants with prostate cancer detected according to PSA density.	The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to the PSA density.	Through study completion, an average of four years.	No
Secondary	Number of participants with prostate cancer detected according to free/total PSA ratio.	The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to the PSA free/total PSA ratio.	Through study completion, an average of four years.	No
Secondary	Number of participants with prostate cancer detected according to prostate volume.	The investigators will also compare the detection rate of 12 versus 20 fragments schemes according to prostate volume.	Through study completion, an average of four years.	No

External Links

•   European society of Urology guidelines on prostate cancer
•   Prostate cancer epidemiology in Brazil.