The Prostate
Prostate Atypia: Does Repeat Biopsy Detect Clinically Significant Prostate Cancer? Ryan P. Dorin,1 Scott Wiener,2 Cory D. Harris, and Joseph R. Wagner2 1
2
Urology Division, Hartford Hospital, Hartford, Connecticut, USA University of Connecticut Health Center, Farmington, Connecticut, USA
Background. While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. Methods. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Results. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein’s criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. Conclusions. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. Prostate # 2015 Wiley Periodicals, Inc. KEY WORDS:
prostate; biopsy; atypia; adenocarcinoma
INTRODUCTION Small groups of atypical glands on needle biopsy suspicious for adenocarcinoma are commonly referred to as prostate atypia. [1,2]. Atypia is a broad diagnostic term that encompasses benign lesions mimicking malignant glandular proliferations and under-sampled, small foci of carcinoma that contain some of the features required for a definitive diagnosis of malignancy. This clinical finding typically only occurs in 5% of biopsies, and is not synonymous with high-grade prostatic intraepithelial neoplasia (HGPIN). Previous studies have reported a significant risk of prostate cancer on subsequent biopsy of prostate atypia [3–8]. However, the likelihood of ß 2015 Wiley Periodicals, Inc.
diagnosing clinically significant prostate cancer on repeat biopsy is not clear.
Conflict of interest: None of the authors have any affiliations that they consider to be relevant and important with any organization that to any author’s knowledge has a direct interest, particularly a financial interest, in the subject matter discussed. Correspondence to: Joseph R. Wagner, MD, Urologic Oncology, Minimally Invasive Surgery, Hartford Specialists, 85 Seymour Street, Suite 416, USA. E-mail: [email protected] Received 30 September 2014; Accepted 26 November 2014 DOI 10.1002/pros.22950 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Dorin et al.
While there is often an established treatment pathway in response to benign or malignant biopsies, there is uncertainty and controversy regarding the prognosis and appropriate clinical course of action when an initial set of prostate biopsy specimens yields a diagnosis of atypia. Most often, an appropriate initial step is to request a series of follow-up biopsies. Clearly, it would be advantageous to both the physician and patient if it were possible to determine the risk of subsequently diagnosing clinically significant prostate in patients with an initial diagnosis of atypia. To address this question, we retrospectively reviewed our large prostate biopsy database, encompassing a 24-year period, to assess both the incidence of prostate atypia in initial biopsy specimens, and subsequent pathologic findings from a repeat biopsy. We also determined the incidence of subsequent treatment for prostate cancer in patients initially diagnosed with atypia, and reviewed the pathologic results of patients who ultimately underwent radical prostatectomy (RP). MATERIALS AND METHODS We retrospectively reviewed our prostate biopsy database containing data prospectively acquired over a 24-year period (November, 1987 – March, 2011). Initial biopsies were triggered by elevated prostate specific antigen (PSA) and/or an abnormal digital rectal exam. Biopsies were performed using ultrasound guidance and individually submitted according to anatomic location. While in 1987, our standard procedure called for only sampling 6 cores, our biopsy protocol was sequentially modified over time in accordance with common practice to include 8, 10, and finally 12 cores. Specifically, 6 cores were routinely sampled from 1987–2003. The biopsy protocol was subsequently changed in 2004, 2005, and 2009 to require the sampling of 8, 10, and 12 cores, respectively (table I). Patients with a prior history of prostate cancer were excluded from our analysis. Patients with at least one biopsy diagnosed as prostate atypia were identified. Pathology results of biopsy specimens were recorded. Prostate cancer diagnosed on repeat
biopsy was classified as “clinically significant” or “clinically insignificant” (clinically organ confined, Gleason sum
Prostate Atypia: Does Repeat Biopsy Detect Clinically Significant Prostate Cancer? Ryan P. Dorin,1 Scott Wiener,2 Cory D. Harris, and Joseph R. Wagner2 1
2
Urology Division, Hartford Hospital, Hartford, Connecticut, USA University of Connecticut Health Center, Farmington, Connecticut, USA
Background. While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. Methods. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Results. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein’s criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. Conclusions. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. Prostate # 2015 Wiley Periodicals, Inc. KEY WORDS:
prostate; biopsy; atypia; adenocarcinoma
INTRODUCTION Small groups of atypical glands on needle biopsy suspicious for adenocarcinoma are commonly referred to as prostate atypia. [1,2]. Atypia is a broad diagnostic term that encompasses benign lesions mimicking malignant glandular proliferations and under-sampled, small foci of carcinoma that contain some of the features required for a definitive diagnosis of malignancy. This clinical finding typically only occurs in 5% of biopsies, and is not synonymous with high-grade prostatic intraepithelial neoplasia (HGPIN). Previous studies have reported a significant risk of prostate cancer on subsequent biopsy of prostate atypia [3–8]. However, the likelihood of ß 2015 Wiley Periodicals, Inc.
diagnosing clinically significant prostate cancer on repeat biopsy is not clear.
Conflict of interest: None of the authors have any affiliations that they consider to be relevant and important with any organization that to any author’s knowledge has a direct interest, particularly a financial interest, in the subject matter discussed. Correspondence to: Joseph R. Wagner, MD, Urologic Oncology, Minimally Invasive Surgery, Hartford Specialists, 85 Seymour Street, Suite 416, USA. E-mail: [email protected] Received 30 September 2014; Accepted 26 November 2014 DOI 10.1002/pros.22950 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Dorin et al.
While there is often an established treatment pathway in response to benign or malignant biopsies, there is uncertainty and controversy regarding the prognosis and appropriate clinical course of action when an initial set of prostate biopsy specimens yields a diagnosis of atypia. Most often, an appropriate initial step is to request a series of follow-up biopsies. Clearly, it would be advantageous to both the physician and patient if it were possible to determine the risk of subsequently diagnosing clinically significant prostate in patients with an initial diagnosis of atypia. To address this question, we retrospectively reviewed our large prostate biopsy database, encompassing a 24-year period, to assess both the incidence of prostate atypia in initial biopsy specimens, and subsequent pathologic findings from a repeat biopsy. We also determined the incidence of subsequent treatment for prostate cancer in patients initially diagnosed with atypia, and reviewed the pathologic results of patients who ultimately underwent radical prostatectomy (RP). MATERIALS AND METHODS We retrospectively reviewed our prostate biopsy database containing data prospectively acquired over a 24-year period (November, 1987 – March, 2011). Initial biopsies were triggered by elevated prostate specific antigen (PSA) and/or an abnormal digital rectal exam. Biopsies were performed using ultrasound guidance and individually submitted according to anatomic location. While in 1987, our standard procedure called for only sampling 6 cores, our biopsy protocol was sequentially modified over time in accordance with common practice to include 8, 10, and finally 12 cores. Specifically, 6 cores were routinely sampled from 1987–2003. The biopsy protocol was subsequently changed in 2004, 2005, and 2009 to require the sampling of 8, 10, and 12 cores, respectively (table I). Patients with a prior history of prostate cancer were excluded from our analysis. Patients with at least one biopsy diagnosed as prostate atypia were identified. Pathology results of biopsy specimens were recorded. Prostate cancer diagnosed on repeat
biopsy was classified as “clinically significant” or “clinically insignificant” (clinically organ confined, Gleason sum
