Predictors of prostate cancer after initial negative systematic 12 core biopsy

PURPOSE: We determined the cancer detection rate at initial systematic 12 core (S12C) biopsy and identified features associated with cancer at repeat S12C biopsy after an initial negative S12C biopsy in patients with prostate specific antigen (PSA) parameters associated with a higher risk of prostate cancer. MATERIALS AND METHODS: Between February 1999 and June 2002, 841 patients underwent initial S12C biopsy. Of these patients 99 underwent repeat S12C biopsy after initial negative S12C because of a percent free-to-total PSA of 15.0 or less and/or a yearly PSA velocity of 0.75 ng/ml or greater. The association between parameters revealed by initial biopsy and cancer at repeat biopsy was assessed. RESULTS: Of the 99 patients 21 (21.2%) had cancer at repeat biopsy. Age (p = 0.01), PSA transitional zone density (p = 0.05), and high grade PIN at initial biopsy (p = 0.01) were associated with cancer at repeat biopsy. CONCLUSIONS: In this select group of patients with PSA parameters associated with a higher risk of prostate cancer the cancer detection rate after initially negative S12C biopsy was 21%. Patients with high grade PIN on initial biopsy, advanced age and higher PSA transition zone density are at increased risk for cancer at repeat biopsy. Larger prospective studies are required to confirm these results and construct a nomogram that determines the probability of finding prostate cancer at subsequent biopsy.     

Prostate cancer detection in men with an initial diagnosis of atypical small acinar proliferation

OBJECTIVE: To determine the subsequent prostatic adenocarcinoma detection rate amongst men with an initial diagnosis of atypical small acinar proliferation (ASAP). PATIENTS AND METHODS: We reviewed the Illawarra Prostate Pathology Database over a 10-year period (January 1994 to January 2004) for specimens diagnosed as ASAP. These specimens were re-reviewed and clinical data obtained. RESULTS: Of 61 cases of ASAP, there were complete follow-up data for 31. In this group nine patients had no further biopsies at our institution; the other 22 had at least one repeat biopsy. The incidence of prostatic adenocarcinoma in this group was 17/31 (55%). This included 13 diagnoses on second biopsy, three on third biopsy and one diagnosed at another institution. CONCLUSION: This study showed a detection rate for prostatic adenocarcinoma of 55% after an initial diagnosis of ASAP, which indicates that an initial diagnosis of ASAP mandates re-biopsy.     

Subsequent prostate cancer detection in patients with prostatic intraepithelial neoplasia or atypical small acinar proliferation

Introduction:

To evaluate the predictors of prostate cancer in follow-up of patients diagnosed on initial biopsy with high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP).

Methods:

We studied 201 patients with HGPIN and 22 patients with ASAP on initial prostatic biopsy who had subsequent prostatic biopsies. The mean time of follow-up was 17.3 months (range 1–62). The mean number of biopsy sessions was 2.5 (range 2–6), and the median number of biopsy cores was 10 (range 6–14).

Results:

On subsequent biopsies, the rate of prostate cancer was 21.9% (44/201) in HGPIN patients. Of these, 32/201 patients (15.9%), 9/66 patients (13.6%) and 3/18 patients (16.6%) were found to have cancer on the first, second and third follow-up biopsy sessions, respectively. In ASAP patients, the cancer detection rate was 13/22 (59.1%), all of whom were found on the first follow-up biopsy. There was a statistically significant difference between the cancer detection rate in ASAP and HGPIN patients (p < 0.001). Multivariate analysis showed that the independent predictors of cancer were the number of cores in the initial biopsy, the number of cores (> 10) in the follow-up biopsy and a prostate specific antigen (PSA) density of ≥ 0.15 (odds ratio 0.77, 3.46 and 2.7,8 respectively; p < 0.04). Conversely, in ASAP patients none of these variables were found to be associated with cancer diagnosis.

Conclusion:

ASAP is a strong predictive factor associated with cancer when compared with HGPIN. The factors predictive of cancer on follow-up biopsy of HGPIN are number of cores on initial biopsy, more than 10 cores in rebiopsy and elevated PSA density. As the cancer detection rate on repeated biopsy of HGPIN patients is the same as that of patients without HGPIN, perhaps the standard of repeat biopsy in all patients with HGPIN should be revisited.Owing to the widespread use of prostate specific antigen (PSA) as a screening tool for prostate cancer associated with increasing use of transrectal ultrasound (TRUS) guided prostate needle biopsy and the increasing number of sampling cores per biopsy, the histological findings of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) has also increased.The detection rate of HGPIN in TRUS-guided needle biopsies performed owing to an elevated PSA level or an abnormal digital rectal examination (DRE), was found to be between 4% and 25% of patients^1–4 and the cancer detection rate on repeated biopsy was reported from 2% to 47% of patients.^1,3,5,6,7 Conversely, the rate of ASAP on initial biopsy was reported to range from 2.4% to 3.7%^3,8,9 the cancer detection rate on repeated biopsy was found to be as high as 52% in isolated ASAP^3,8,10 and 72% in ASAP associated with HGPIN.^3,11The management of patients found to have HGPIN on initial biopsy varies considerably, ranging from immediate rebiopsy to close observation at varying intervals.^12–15 Our aim was to examine our experience with prostatic rebiopsy in patients with HGPIN, ASAP or both.     

Repeat biopsy strategy in patients with atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia on initial prostate needle biopsy

PURPOSE: Isolated high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation on prostate biopsy increases the risk of identifying cancer on repeat biopsy. We report the results of repeat prostate biopsy for high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation, and propose an optimal repeat biopsy strategy. MATERIALS AND METHODS: Of 1,391 men who underwent standard systematic sextant biopsy of the prostate 137 (9.8%) had isolated high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation, including 100 who underwent repeat prostate biopsy within 12 months of the initial biopsy. RESULTS: Adenocarcinoma was detected in 47 of the 100 patients who underwent repeat biopsy. The initial biopsy site of high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation matched the sextant location of cancer on repeat biopsy in 22 cases (47%). Repeat biopsy directed only to the high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation site on initial biopsy would have missed 53% of cancer cases. In 12 of the 47 men (26%) cancer was limited to the side of the prostate contralateral to the side of high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation. Of the 31 patients with cancer in whom the transition zone was sampled cancer was limited to the transition zone in 4 (13%) and evident at other biopsy sites in 13 (42%). The only significant predictor of positive repeat biopsy was mean prostate specific antigen velocity plus or minus standard error (1.37 +/- 1.4 versus 0.52 +/- 0.8 ng./ml. per year, p <0.001). CONCLUSIONS: Patients with isolated high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation on prostate biopsy are at 47% risk for cancer on repeat biopsy. The optimal repeat biopsy strategy in this setting should include bilateral biopsies of the standard sextant locations. We also strongly recommend that transition zone sampling should be considered.     

Atypical small acinar proliferation at index prostate biopsy: rethinking the re-biopsy paradigm

Purpose

Guidelines for atypical small acinar proliferation (ASAP) diagnosed on prostate biopsy recommend repeat biopsy within 3–6 months after diagnosis. We sought to discern the rate of detecting clinically significant prostate cancer on repeat biopsy and predictors associated with progression.

Materials and methods

We performed a retrospective chart review of patients who underwent prostate biopsy at our institution from January 1, 2008, to December 31, 2015. Gleason grade group (GGG) system and D’Amico stratification were used to report pathology and risk stratification, respectively. Logistic and linear regression analyses were performed.

Results

A total of 593 patients underwent transrectal ultrasound-guided prostate biopsy, of which 27 (4.6%) had the diagnosis of ASAP. Of these, 11 (41%) had a repeat biopsy. Median time from diagnosis to repeat biopsy was 147 days (IQR 83.5–247.0). Distribution across the GGG system on repeat biopsy was as follows: 7 (63.6%) benign, 3 (27.3%) GG1, and 1 (9.1%) GG2. ASAP was not associated with subsequent diagnosis of clinically significant prostate cancer (OR 0.46, 95% CI 0.064–3.247, P = 0.432). There was no association between ASAP and high cancer risk (ASAP: β = ? 0.12; P = 0.204).

Conclusions

Patients diagnosed with ASAP managed according to guideline recommendations are more likely diagnosed with benign pathology and indolent prostate cancer on repeat biopsy. These findings support prior studies suggesting refinement of guidelines in regard to the appropriateness and timeliness of repeat biopsy among patients diagnosed with ASAP.

     

The presence of atypical small acinar proliferation in prostate needle biopsy is predictive of carcinoma on subsequent biopsy

OBJECTIVE: To determine the clinical significance of nondiagnostic small acini showing cellular atypia (atypical small acinar proliferation) in prostatic biopsies of patients with clinical findings suggestive of malignancy. PATIENTS AND METHODS: Of 331 patients who underwent thin-core biopsy of the prostate over a 30-month period, 21 (6.3%) had atypical histological features, and of these 17 underwent repeat biopsy. In addition, a further 20 patients with normal histology underwent repeat biopsy for persistent abnormal clinical findings. The incidence and Gleason score of carcinomas subsequently diagnosed in the two groups were compared. The predictive significance of patient age, prostate specific antigen (PSA) level and digital rectal examination (DRE) findings were compared between both patient groups, those in each group subsequently found to have carcinoma, and between patients with malignant or normal repeat biopsies who had either atypical or normal initial biopsies. RESULTS: Nine patients with atypical histology and four with normal histology on initial biopsy were found to have carcinoma on subsequent biopsy (P = 0.036). The site of carcinoma diagnosed in the repeat biopsy frequently differed from that of the initial atypical biopsy. The Gleason primary pattern was not significantly different between the groups. Neither patient age, PSA level nor DRE findings differed between patients with initial normal or atypical biopsy, or in these groups for those in whom carcinoma was subsequently diagnosed. These clinical features did not distinguish between those with carcinoma or normal findings on repeat biopsy who had an initial atypical biopsy, while only PSA level varied significantly in patients with normal or malignant repeat biopsy in the group with an initial normal biopsy. CONCLUSION: The presence of atypia on initial biopsy is a strong predictor of malignancy in subsequent biopsy specimens.     

High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation: predictive value for cancer in current practice

In earlier studies, prostate cancer (PCa) has been reported to appear in 21% to 48% of subsequent biopsies for isolated high-grade prostatic intraepithelial neoplasia (PIN) and in 34% to 60% for isolated atypical small acinar proliferation suspicious for, but not diagnostic of, malignancy (ASAP). We report results of follow-up biopsies in a recent cohort of community practice patients who underwent biopsy for PSA abnormalities. The study group consisted of 336 men with initial diagnoses of PIN (n = 204), ASAP (n = 78), or both lesions (n = 54) who underwent at least one repeat biopsy. Mean follow-up intervals in months were 6.0 for PIN, 3.8 for ASAP, and 4.9 for PIN/ASAP. Follow-up PCa detection rates were 23%, 37%, and 33%, respectively. The predictive value of ASAP was significantly higher than that for PIN (P = 0.0188). In 23 PIN studies with chronologic midpoints in the early 1990s, follow-up PCa was detected in a mean of 36% of cases, whereas this value was 21% after the year 2000. In 13 ASAP studies, mean PCa detection on follow-up was 45% until 1996 and 39% from 1997 to present. PIN/ASAP predicted PCa in 33% of cases in our study, similar to ASAP alone (P = 0.65) and had a mean predictive value of 44% in the literature. Factors that may account for the decline in PIN predictive values include: 1) extended biopsy techniques that yield higher rates of initial cancer detection, 2) lower detection rate for the remaining small cancers that may accompany PIN, and 3) remaining PIN cases may lack concomitant cancer.     

Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

BACKGROUND: Currently, there are no clear criteria for indicating repeat biopsies in patients with negative results at an initial biopsy of the prostate. The aim of the present study is to determine the clinical and pathological parameters which predict prostate cancer at repeat biopsies with special attention to the interval between biopsies in addition to prostate specific antigen (PSA) and its derivatives. METHODS: We reviewed 100 patients who underwent an initial biopsy that proved negative for prostate cancer and required repeat biopsies between November 1996 and November 2003. Clinical parameters such as age, PSA and its derivatives, interval between biopsies, number of cores taken and initial biopsy histology were analyzed. RESULTS: In total, 31 patients (31.0%) were found to have prostate cancer, 18 (25.7%) of 70 patients by the second biopsy and 13 (46.4%) of 28 patients by the third biopsy. Two patients underwent the fourth biopsy, which revealed no prostate cancer. The patients with a positive biopsy had a significantly longer interval between the biopsies than the patients with a negative biopsy (P=0.0036). Furthermore, in both univariate and multivariate logistic regression analysis, only the interval between the biopsies proved to be an independent predictor of positive results at repeat biopsies (P=0.0094 and 0.0019). CONCLUSIONS: Only the biopsy interval was a significant predictor of prostate cancer at repeat biopsies in both univariate and multivariate analysis.