The purpose of this study was to analyze the characteristics of initially missed and rebiopsy-detected prostate cancers following 12-core transrectal biopsy.
A total of 45 patients with prostate cancers detected on rebiopsy and 45 patients with prostate cancers initially detected on transrectal ultrasound-guided biopsy were included in the study. For result analysis, the prostate was divided into six compartments, and the cancer positive rates, estimated tumor burden, and agreement rates between biopsy and surgical specimens, along with clinical data, were evaluated.
The largest mean tumor burden was located in the medial apex in both groups. There were significantly more tumors in this location in the rebiopsy group (44.9%) than in the control group (30.1%, P=0.015). The overall sensitivity of biopsy was significantly lower in the rebiopsy group (22.5% vs. 43.4%, P<0.001). The agreement rate of cancer positive cores between biopsy and surgical specimens was significantly lower in the medial apex in the rebiopsy group compared with that of the control group (50.0% vs. 65.6%, P=0.035). The cancer positive rates of target biopsy cores and premalignant lesions in the rebiopsy group were 63.1% and 42.3%, respectively.
Rebiopsy-detected prostate cancers showed different spatial distribution and lower cancer detection rate of biopsy cores compared with initially diagnosed cancers. To overcome lower cancer detection rate, target biopsy of abnormal sonographic findings, premalignant lesions and medial apex which revealed larger tumor burden would be recommended when performing rebiopsy.
Prostate cancer is the second most common malignancy in men, and its incidence is rapidly increasing with prostate-specific antigen (PSA)-based screening [
12-Core systematic biopsy has been routinely performed under sonographic guidance as TRUS has limitations for cancer detection due to its low sensitivity and variable accuracy [
Mazal et al. [
This retrospective study was approved by our Institutional Review Board, and the requirement for informed consent was waived.
Between January 2005 and June 2013, we identified 719 patients with negative results for cancer on initial TRUS-guided 12-core biopsy followed by a repeat biopsy performed at our medical institution. Among them, 241 patients who underwent repeat TRUSguided biopsy within 12 months after the initial negative biopsy were identified. The remaining 478 patients, who underwent repeat biopsy more than 12 months after the initial biopsy, were excluded. Indications for repeat biopsy were (1) persistently elevated PSA level (>3.0 ng/mL) or (2) initial atypical results of either atypical small acinar proliferation (ASAP) or prostatic intraepithelial neoplasia (PIN) [
Between June 2012 and June 2013, a total of 470 patients with initially detected prostate cancer on TRUS-guided 12-core biopsy were collected. The TRUS-guided biopsy was performed following the detection of an elevated PSA level (>3.0 ng/mL). These control patients were matched 1:1 with the rebiopsy group according to PSA level (±0.5). After excluding 10 patients without surgical specimens, 45 patients were selected as the control group.
Before TRUS-guided prostate biopsy, all patients provided written, informed consent. The prostate biopsy procedure was as follows: fluoroquinolone antibiotics were administered orally for 3 days before the biopsy and intravenous injection of cephalosporin antibiotics was administered just before the biopsy. A bowelcleansing enema was done on the morning of the biopsy. All patients received local anesthesia using a 22-gauge spinal needle passed through the biopsy guide channel with 10 mL 2% lidocaine injected into each neurovascular bundle. The three-dimensional diameter of the prostate was measured using a Sequoia 512 unit (Acuson, Montain View, CA, USA) or a Philips IU-22 unit (Philips Ultrasound, Bothell, WA, USA) and a 7-MHz probe. The prostate volume was then calculated according to the prolate ellipsoid formula (length×width×height×π/6). Prostate cancers were usually indistinguishable from benign prostatic hyperplasia (BPH) nodules on TRUS; however, hypoechoic focal lesions or protruding bulky masses with increased vascularity were sometimes suspected to be malignant (
The 12-core biopsy scheme is illustrated in
Pathology assessment of the biopsy core included the length of the core, the number and location of positive cores, the percent of cancer involvement in any positive core, and the biopsy Gleason score. The histopathological analysis was based on the standard 12-core biopsy scheme as mentioned above. For radical prostatectomy specimens, several board-certified pathologists created a pathologic map of the prostate cancer in each patient after processing the surgical specimen, as described in a previous report [
We combined the right and left prostate gland, simplifying 12 compartments into six compartments; i.e., A, right lateral base and G, left lateral base as A+G; B, right lateral middle and H, left lateral middle as B+H; C, right lateral apex and I, left lateral apex as C+I; D, right medial base and J, left medial base as D+J; E, right medial middle and K, left medial middle as E+K; and F, right medial apex and L, left medial apex as F+L (
Since the control group was selected by 1:1 matching with the rebiopsy group, paired t tests and marginal homogeneity tests were used to compare clinical data such as age, prostate volume, number of cancer positive biopsy cores and cancer positive surgical compartments, surgical Gleason scores, and pathologic tumor stage. The cancer positive rates on biopsy cores and surgical specimen and the agreement rates of biopsy and surgical specimens were compared using a McNemar test for paired data. The estimated tumor burden was presented as mean percentage (%) and absolute tumor volume (mL) and the biopsy sensitivity in each compartment was compared using t test or Mann-Whitney U test and Fisher exact test or chi-square test, respectively. A P-value less than 0.05 was deemed significant when comparing between the two groups.
The clinical data from the control and rebiopsy groups are presented in
The mean biopsy interval was 4.8±3.2 months (range, 2 to 12 months), with a maximum interval of 12 months. The PSA level (initial vs. repeat biopsy, 6.42±4.51 vs. 6.74±4.63) and PSA density (initial vs. repeat biopsy, 0.18±0.15 vs. 0.16±0.16) were not changed between the two events (P>0.05). Pathologic results of 45 cases in the initial needle biopsy showed ASAP (n=18), PIN (n=8), or no cancer (n=19).
The mean tumor volume of all six compartments was 11.38±12.24 mL in the control group and 4.31±4.82 mL in the rebiopsy group. The control group showed a significantly larger mean tumor burden than the rebiopsy group (P<0.001). The spatial distributions of cancer volume in the control and the rebiopsy groups are listed in
The highest cancer positive rate on the biopsy cores was found in the medial apex in both the rebiopsy (22.2%) and control groups (36.7%). When comparing the two groups, the control group had significantly higher cancer positive rates in the medial and lateral middle and medial and lateral apex than the rebiopsy group (P<0.05) (
In the rebiopsy group, the cancer positive rate of target biopsy cores was 63.1% (12/19) and the rate of ASAP or PIN was 42.3% (11/26); these rates were higher than those in all the other six compartments in both the rebiopsy and control groups.
The highest cancer positive rate on the surgical specimens was found in the medial apex in both the rebiopsy (62.2%) and control groups (80.0%). When comparing the two groups, the control group had a significantly higher cancer positive rate in the medial base, medial and lateral middle, and medial apex than the rebiopsy group (P<0.05) (
The sensitivity of core biopsy and the agreement rates between the biopsy and surgical specimens in the two groups are presented in
Our results indicate that initially missed and rebiopsy-detected prostate cancer showed significantly smaller overall tumor burden and lower sensitivity of biopsy cores. Among the six compartments measured, excluding the medial base that showed little tumor burden, the rebiopsy group showed a smaller tumor burden in four compartments (lateral base, medial and lateral middle, and lateral apex) and a larger tumor burden in the medial apex. That is, rebiopsy-detected prostate cancers tended to be more commonly distributed in the medial apex, in contrast to the relatively even tumor distribution in initially detected prostate cancers. The smaller tumor burden in the rebiopsy group probably led to the lower sensitivity of the biopsy cores. Similarly, the rebiopsy group showed lower cancer positive rates on biopsy and surgical specimens in more than half of the six compartments compared with the control group. In spite of the difference in tumor burden between the rebiopsy and the control groups, there was no difference in biochemical and histopathologic parameters, including the mean PSA level, PSA range, mean surgical Gleason score, and pathologic tumor stage. This is somewhat contrary to previous reports of a correlation between PSA level and tumor burden. Verim et al. [
Although the largest tumor burden in the rebiopsy group was found in the medial apex, the agreement rate of cancer positive cores between the biopsy and surgical specimens in the medial apex was significantly lower compared with the control group. Prostate cancers located in the apex can lower the cancer detection rate and are frequently the cause of false-negative results on TRUS-guided prostate biopsy [
The cancer positive rate of previous atypical results such as ASAP and PIN was 42.3% in our study, which was comparable with previous reports [
The adequate sampling number has not yet been determined. Aganovic et al. [
Our TRUS biopsy procedure and histopathologic analysis were based on a standard 12-biopsy scheme on both initial and repeat biopsy. We did not consider alternative sampling templates as proposed by others [
In our study, the maximum interval between initial and repeat biopsy was 12 months. There is little data regarding the criteria for differentiating
Our study has some limitations. First, there might be some discrepancy in the correlation between 12-core prostate biopsy results and those of the pathologic map of the surgical specimen. However, this type of discrepancy is somewhat inevitable as it stems from random prostate biopsy procedure itself. Second, we calculated the tumor burden using Photoshop after drawing ROIs manually. Therefore, there could have been errors in calculating small tumor foci, which were frequently observed in the rebiopsy group, in contrast to the confluent larger tumors observed in the control group. Third, this study is retrospective, and our analysis is confined to the standardized 12-core biopsy scheme used in clinical practice at our institution and does not consider alternative biopsy templates or direct targeting of the transition zone. However, the transition zone can be included in both medial compartments, and the 12- core biopsy scheme has been applied in many other centers. Further studies, including an increased number of biopsy cores or image-guided target biopsy, would be helpful additions to our study.
In conclusion, initially missed prostate cancers appear to have a smaller tumor burden with larger prostate volume and lower sensitivity rate of biopsy cores than those of initially diagnosed prostate cancers. The largest tumor burden might be located in the medial apex, with a significantly lower agreement rate between biopsy and surgical specimens in rebiopsied individuals. Target biopsy of abnormal sonographic findings or premalignant lesions such as ASAP or PIN might show higher cancer positive rates than systematic 12-core routine biopsy.
No potential conflict of interest relevant to this article was reported.
This study was supported in part by the Research Fund of the Korean Society of Ultrasound in Medicine.
Cancer positive rates on biopsy cores in control and rebiopsy groups (
Cancer positive rates on surgical specimens in control and rebiopsy groups (
A. The TRUS image reveals a cancerous mass in the apex of the central gland (arrows) as a hypoechoic focal lesion. B. The corresponding pathology map shows a bilateral tumor mass in the medial apex.
The prostate gland is divided into 12 compartments. A, right lateral base; B, right lateral middle; C, right lateral apex; D, right medial base; E, right medial middle; F, right medial apex; G, left lateral base; H, left lateral middle; I, left lateral apex; J, left medial base; K, left medial middle; L, left medial apex.
Comparison of clinical data in control and rebiopsy groups
Characteristic | Control (n=45) | Rebiopsy (n=45) | P-value |
---|---|---|---|
Age (yr) | 66.69±8.66 | 64.24±7.32 | 0.105 |
Prostate volume (mL) | 33.14±12.21 | 40.79±20.71 | 0.032 |
No. of positive biopsy cores | 3.64±2.19 | 2.00±1.25 | <0.001 |
No. of positive cores in the surgical specimen | 6.62±2.78 | 4.95±2.81 | 0.014 |
Surgical Gleason score | 0.481 | ||
6 | 12 (26.7) | 15 (33.3) | |
7 | 25 (55.6) | 26 (57.8) | |
8 | 4 (8.9) | 3 (6.7) | |
9 | 4 (8.9) | 1 (2.2) | |
Pathologic tumor stage | 0.116 | ||
T2a | 2 (4.4) | 7 (15.6) | |
T2b | 3 (6.7) | 4 (8.9) | |
T2c | 27 (60.0) | 29 (64.4) | |
T3a | 13 (28.9) | 5 (11.1) |
Values are presented as mean±SD or number (%).
Estimated tumor burden on surgical specimens in control and rebiopsy groups
Variable | Control | Rebiopsy | P-value | |
---|---|---|---|---|
Mean tumor volume of all six compartments (mL) | 11.38±12.24 | 4.31±4.82 | <0.001 | |
Base (right, left) | Medial | 0.58±0.85 (8.4±5.8) | 0.32±0.26 (16.3±18.5) | 0.620 (0.244) |
Lateral | 0.44±0.57 (10.4±15.9) | 0.37±0.66 (10.6±12.6) | 0.043 (0.479) | |
Middle (right, left) | Medial | 1.35±1.31 (26.1±14.3) | 0.62±0.86 (29.8±25.7) | 0.004 (0.526) |
Lateral | 1.13±0.87 (28.8±17.7) | 0.51±0.46 (34.8±29.6) | 0.001 (0.324) | |
Apex (right, left) | Medial | 0.93±1.05 (30.1±21.1) | 0.71±0.87 (44.9±29.5) | 0.112 (0.015) |
Lateral | 0.69±0.99 (21.9±16.9) | 0.28±0.25 (23.5±23.7) | 0.007 (0.778) |
Values are mean tumor volume (mL)±standard deviation in each compartment (mean percentage of tumor burden±standard deviation in each compartment).
Sensitivity of biopsy in control and rebiopsy groups
Variable | Control | Rebiopsy | P-value | |
---|---|---|---|---|
Total (540 compartments) | 129/297 (43.4) | 50/222 (22.5) | <0.001 | |
Base (right, left) | Medial | 8/25 (32.0) | 3/13 (23.1) | 0.714 |
Lateral | 10/26 (38.5) | 4/18 (22.2) | 0.333 | |
Middle (right, left) | Medial | 24/56 (42.9) | 4/38 (10.5) | 0.001 |
Lateral | 27/58 (46.5) | 12/45 (26.7) | 0.039 | |
Apex (right, left) | Medial | 30/72 (41.7) | 19/56 (33.9) | 0.372 |
Lateral | 30/60 (46.7) | 8/52 (15.4) | <0.001 |
Values are presented as number (%).
Sensitivity=Number of cancer positive compartments on biopsy agreeing with that on surgical specimen/Number of cancer-positive compartments on the surgical specimen.
Agreement rate of cancer positive cores between biopsy and surgical specimens
Variable | Control | Rebiopsy | P-value | |
---|---|---|---|---|
Total (540 compartments) | 340/540 (63.0) | 338/540 (62.6) | 0.899 | |
Base (right, left) | Medial | 61/90 (67.8) | 70/90 (77.8) | 0.149 |
Lateral | 67/90 (74.4) | 65/90 (72.2) | 0.732 | |
Middle (right, left) | Medial | 54/90 (60.0) | 51/90 (56.7) | 0.662 |
Lateral | 54/90 (60.0) | 55/90 (61.1) | 0.879 | |
Apex (right, left) | Medial | 59/90 (65.6) | 45/90 (50.0) | 0.035 |
Lateral | 45/90 (50.0) | 52/90 (57.8) | 0.274 |
Values are presented as number (%).
Agreement rate=Number of cancer positive compartments on biopsy agreeing with that on surgical specimen/Total number of compartments.