Predicting Cancer Following a Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia on Needle Biopsy

Abstract

Most studies on the risk of cancer after high-grade prostatic intraepithelial neoplasia (PIN) on biopsy have been small (fewer than 100 men), have not analyzed in detail if histologic features can predict cancer, and have not assessed the risk of cancer with multiple repeat biopsies. We analyzed 245 men in whom the only abnormal finding on the initial biopsy was high-grade PIN and who had at least one follow-up biopsy. Repeat biopsy identified cancer in 32.2% of men. If only one follow-up biopsy had been performed on the 245 men, only 24.5% of men would have been found to have cancer. The only independent histologic predictor of a cancer diagnosis was the number of cores with high-grade PIN; risk of cancer: 30.2% with 1 or 2 cores, 40% with 3 cores, and 75% with >3 cores. The following did not predict cancer: number of high-grade PIN glands, maximum percentage of gland involved by high-grade PIN, nucleolar prominence, percentage of cells with prominent nucleoli, pattern of high-grade PIN (flat, tufting, micropapillary, cribriform), marked pleomorphism, digital rectal examination, transrectal ultrasound findings, family history of prostate cancer, serum prostate specific antigen (PSA) at time of high-grade PIN diagnosis, and rate of change of serum PSA. Eighty-one (33%) men had more than one follow-up biopsy; in these cases the following findings on the original high-grade PIN biopsy predicted cancer: the presence of mitoses, the number of positive cores, predominant micropapillary and cribriform high-grade PIN, and very large prominent nucleoli. Of 81 men with more than one follow-up biopsy, if the first repeat biopsy were benign, high-grade PIN, or atypical, the eventual cancer rate was 10%, 25.9%, and 57.1%, respectively (p = 0.002). Of 15 men with more than two repeat biopsies, only two (13.3%) had cancer. In summary, approximately one third of men with high-grade PIN on biopsy have cancer on follow-up. If cancer is not found on the first two follow-up biopsies, it will unlikely be found. Although clinical findings at the time of diagnosis of high-grade PIN are not useful to predict who might have cancer, histologic findings may help identify who needs additional biopsies.

Is High Grade Prostatic Intraepithelial Neoplasia a Risk Factor for Prostate Cancer?—A Local Study

“…This finding was in consistence with Kronz et al [26] and Schoenfield et al [20] who found cancer of the prostate on the 2 nd biopsy in third of their patients having HGPIN on the 1 st biopsy with higher rate of cancer detection in multifocal than unifocal HGPIN. This indicates that the prostate cancer risk is increased with the increase in the number of specimens found to have HGPIN on the 1 st biopsy.…”

Current practice of diagnosis and reporting of prostatic intraepithelial neoplasia and glandular atypia among genitourinary pathologists

“…Several studies have shown that cribriform PIN conveys an increased risk of developing into invasive cancer compared to other types of PIN. 16,17 Others have failed to confirm this finding. 18 The split opinion on the prognostic impact of PIN architecture may explain that only 19% of respondents specified architectural patterns in needle biopsy reports.…”

“…Initially, a high risk was reported, usually in the interval of 30-40%. 17,19 16,18,20 The decreased predictive value for cancer may be explained by an increasing number of cores in each biopsy session. When no cancer is found in multiple biopsy cores, the risk of missing an invasive cancer is evidently lower than when a limited number of cores are taken.…”

“…16,17 In contrast, others have failed to demonstrate an increased risk of cancer with multiple cores involved. 18,22 The number of cores with HGPIN was only reported by 50% of survey respondents reflecting the conflicting data on this issue.…”

Digital quantification of precursor frequency in the fallopian tube and its significance

“…However, resolving the importance of these disparate events requires attention to confounding variables such as age and equally important, the intrinsic sampling variation across different tissue sections, each with presumably different amounts of epithelium. 14 Numerous examples in the literature attest to the importance of ascertaining precursor frequency or size as a surrogate for cancer risk, such as in the colon, pancreas and prostate, [15][16][17][18][19][20][21][22][23][24] These organs house early epithelial changes that are not unlike the SCOUTs described in the fallopian tube. As high precursor frequencies could signal an acquired or underlying familial tendency for cancer development, precise quantification of the epithelial perimeter at risk is paramount.…”