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PROSTATE CANCER DETECTION WITH OFFICE BASED SATURATION BIOPSY IN A REPEAT BIOPSY POPULATION
0022-5347/04/1721-0094/0 THE JOURNAL OF UROLOGY® Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 172, 94 –97, July 2004 Printed in U.S.A.
DOI: 10.1097/01.ju.0000132134.10470.75
PROSTATE CANCER DETECTION WITH OFFICE BASED SATURATION BIOPSY IN A REPEAT BIOPSY POPULATION JOHN C. RABETS, J. STEPHEN JONES,*,† AMIT PATEL
AND
CRAIG D. ZIPPE‡
From the Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
Purpose: Patients at increased risk for prostate cancer with previously negative biopsies pose a diagnostic challenge. We have previously demonstrated that extensive saturation biopsy can be performed in an office setting. We now report the diagnostic yield of office saturation biopsy in patients at increased risk for prostate cancer and at least 1 negative prior biopsy. Materials and Methods: We performed saturation prostate biopsy with local anesthesia in the office in 116 patients with at least 1 prior negative biopsy and with certain risk factors, namely persistently elevated prostate specific antigen, abnormal digital rectal examination, or prior atypia or PIN on prior biopsy. Results: A total of 34 cancers were detected for an overall diagnostic yield of 29%. A 64% detection rate was noted when a patient had undergone a single prior sextant biopsy. Subgroup analysis revealed a cancer detection rate of 41% when only prior sextant biopsies were performed, and a 24% detection rate when 10 or more cores were taken on prior biopsy. The detection rate was 33% when only 1 prior biopsy was taken and it was 24% when 2 or more prior biopsies were performed. Conclusions: Saturation biopsy can be performed safely and effectively in the office with a significant diagnostic yield even in patients with previous extended biopsy schemes. We believe that it should be the next diagnostic step after an initial negative biopsy in patients in whom the diagnosis of prostate cancer is strongly suspected. KEY WORDS: prostate, prostatic neoplasms, biopsy, ambulatory surgical procedures, ultrasonography
neurovascular bundle. Without delay 24 biopsies were obtained with a spring loaded biopsy gun. The 12 locations on either side were the lateral base (2), lateral mid zone (3), apex (3), parasagittal mid zone (2) and parasagittal base (2) (fig. 1). After analyzing the site specific cancer detection rate using this 24 core saturation biopsy scheme in the first 80 patients we noted that medial parasagittal cores were never positive in the absence of apical, lateral mid zone or lateral base positivity (fig. 2, B). We then changed our biopsy scheme to include only 1 parasagittal mid zone and 1 parasagittal base biopsy from each side, thus, decreasing the total number of cores sampled from 24 to 20 in the last 36 patients.
Random, systematic, ultrasound guided prostate biopsy has vastly improved the ability to diagnose prostate cancer. There exists a challenging cohort of patients with substantial risk factors for prostate cancer who have had previously negative biopsies. For these patients extensive saturation biopsy may be appropriate. However, some urologists are reluctant to perform this procedure, which has been historically performed as an outpatient surgical procedure with anesthesia support. Our group reported that saturation biopsy may be performed safely and with minimal patient discomfort in the urologist office using local anesthesia.1 We now report the diagnostic yield of office saturation biopsy in a repeat biopsy population. METHODS
RESULTS
A total of 116 consecutive patients who were believed to be at increased risk for prostate cancer after at least 1 negative prior biopsy were chosen to undergo office saturation biopsy. Indications were prior PIN or atypia on previous biopsies, prostate specific antigen (PSA) persistently greater than 2.5 ng/dl or an abnormal digital rectal examination (DRE). After obtaining informed consent saturation biopsy with local anesthesia was performed, as described previously.1 Briefly, the patient was placed in the left lateral decubitus position and the ultrasound probe was placed transrectally. A 22 gauge spinal needle was passed through the biopsy guide channel and 10 cc 1% lidocaine was injected into each
A total of 116 consecutive patients underwent saturation biopsy between February 2002 and September 2003. Table 1 lists patient characteristics. Mean age in this cohort was 62 years (range 47 to 83) and mean PSA was 9.2 ng/dl (range 1.7 to 48.6). All patients had localized disease on clinical examination. The mean number of prior biopsies was 1.7 (range 1 to 7). The indication for repeat biopsy was PIN in 33% of cases or atypia in 8% on prior biopsy, abnormal DRE in 12% and increased PSA (greater than 2.5 ng/dl) in 47%. Adenocarcinoma was diagnosed in 34 patients for an overall diagnostic yield of 29%. Cancer was detected in 23 of 70 patients (33%) with only 1, 7 of 28 (25%) with 2 and 4 of 18 (22%) with 3 or more prior biopsies (table 2). Complete information regarding the number of cores taken in the 70 patients who had only a single prior biopsy session was available on 59. Cancer was detected in 7 of the 11 patients (64%) who only had a single prior sextant biopsy. Mean PSA in this group of 7 patients diagnosed with cancer was 8.9 ng/dl (range 2.4 to 21.7). One of the 7 patients had PIN on prior biopsy and 3 had abnormal DRE.
Accepted for publication February 13, 2004. * Correspondence: 9500 Euclid Ave., Suite A100, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195 (telephone: 216-839-3666; FAX: 216-839-3660; e-mail: [email protected]). † Financial interest and/or other relationship with Pfizer, Abbott and Cook. ‡ Financial interest and/or other relationship with Pfizer, AstraZeneca and TAP. 94
95
CANCER DETECTION WITH OFFICE SATURATION PROSTATE BIOPSY
TABLE 1. Demographic information and indications in patients undergoing saturation biopsy
FIG. 1. Number and locations of cores sampled for saturation biopsy.
The cancer detection rate was 21% (3 of 14) and 11% (3 of 27) when patients underwent a single 8 and 10 core biopsy session, respectively. Three of the 7 patients who had a single biopsy session in which 12 or more cores were obtained were diagnosed with cancer. Complete records regarding the total number of cores taken per previous biopsy were available on 97 patients (table 2). Of our patients 78% had previous biopsy sessions in which more than 6 cores were obtained. Cancer was detected in 9 of 22 patients (41%) with only prior sextant biopsies (1 or more prior biopsy sessions), in 5 of 16 (31%) with prior 8 core biopsies, in 9 of 41 (22%) with prior 10 core biopsies, in 2 of 8 (25%) with 12 core biopsies and in 3 of 10 (30%) with prior 14 plus core biopsies. In the group diagnosed with cancer after 14 or more cores were taken at prior biopsy sessions mean PSA was 12.2 ng/dl (range 8.9 to 16.7). The mean number of prior biopsies was 2.7 (range 1 to 5). Two patients had a history of PIN and none had abnormal DRE. All 3 patients underwent saturation biopsy within 3 years of the most recent biopsy. Two patients were diagnosed with Gleason score 3⫹3 cancer and 1 had Gleason score 5⫹4 cancer.
No. pts Mean age (range) Mean ng/dl PSA (range) Mean No. prior biopsies (range) No. saturation biopsy indication (%): Prior biopsy PIN Prior biopsy atypia Abnormal DRE Increased PSA No. prior biopsy sessions (%): 1 2 3⫹ No. prior biopsy cores (%): 6 8 10 12 14⫹ No. cores sampled in pts with 1 prior biopsy session (%): 6 8 10 12 14⫹
116 62 (47–83) 9.2 (1.7–48.6) 1.7 (1–7) 116 38 (33) 9 (8) 14 (12) 55 (47) 116 70 (60) 28 (24) 18 (16) 97 22 (23) 16 (17) 41 (42) 8 (8) 10 (10) 59 11 14 27 3 4
(19) (24) (46) (5) (7)
Table 2 shows the cancer yield by indication and PSA. Seven of 38 patients (18%) with a history of PIN had cancer, while cancer was detected in 1 of 9 (11%) with a history of atypia, 5 of 14 (36%) with abnormal DRE and 21 of 55 (38%) whose only indication for repeat biopsy was increased PSA. The cancer detection rate was 20%, 25%, 38% and 50% in patients with PSA less than 2.5, between 2.5 and 10, between 10 and 20, and greater than 20 ng/dl, respectively. Figure 2 shows the location of positive cores. A total of 21 patients were diagnosed with prostate cancer using the initial 24 core biopsy scheme. Figure 2, A shows the locations of biopsy positivity. Of the patients 13 were diagnosed with cancer using the subsequent 20 core scheme. Figure 2, B shows the positivity of exclusively lateral (including apical, lateral mid zone and lateral base biopsies), exclusively medial (including parasagittal mid and parasagittal base) or lateral and medial biopsy positivity. There were no positive parasagittal (medial) cores in the absence of lateral core positivity. In the 34 patients in whom cancer was diagnosed mean age was 65.2 years and mean PSA was 9.9 ng/dl (table 3). Gleason score 6 and 7 cancer was noted in 23 (68%) and 7
FIG. 2. A, location of positive cores in 21 patients diagnosed with cancer who underwent original 24 core biopsy scheme. B, location of biopsy positivity in all 34 patients. Apical, lateral base and lateral mid zone were considered lateral and parasagittal biopsies were considered medial. There were no exclusively positive medial cores.
96
CANCER DETECTION WITH OFFICE SATURATION PROSTATE BIOPSY TABLE 2. Cancer detection rates
TABLE 4. Prostatectomy specimen characteristics
No. pts No. Ca detected (%) No. Ca detection/No. prior biopsy sessions/total No. (%): 1 2 3⫹ No. Ca detection/No. cores sampled on prior biopsy/total No. (%): 6 8 10 12 14⫹ No. Ca detection/No. cores sampled in pts with 1 prior biopsy session/total No. (%): 6 8 10 12 14⫹ No. indication Ca detection/total No. (%): Prior biopsy PIN Prior biopsy atypia Abnormal DRE Elevated PSA No. ng/ml PSA Ca detection/total No. (%): 0–2.5 2.5–10 10–20 Greater than 20
116 34 (29) 23/70 (33) 7/28 (25) 4/18 (22) 97 9/22 (41) 5/16 (31) 9/41 (22) 2/8 (25) 3/10 (30) 59 7/11 (64) 3/14 (21) 3/27 (11) 2/3 (66) 1/4 (25) 7/38 (18) 1/9 (11) 5/14 (36) 21/55 (38) 1/5 (20) 20/79 (25) 10/26 (38) 3/6 (50)
TABLE 3. Diagnosed cancers and treatments chosen No. Ca diagnosed Mean age (range) Mean PSA (range) No. Gleason score (%): 4 5 6 7 8 9 No. treatment (%): Radical prostatectomy External beam radiation Brachytherapy Hormonal ablation Watchful waiting Undecided
34 65 (51–80) 9.9 (2.4–23.4) 2 1 23 7 0 1
(6) (3) (68) (21)
7 4 13 2 4 4
(20) (12) (38) (6) (12) (12)
(3)
patients (21%), respectively, while 3 had a Gleason score of 4 or 5 and 1 had a Gleason score of 9. Seven patients elected radical prostatectomy, 13 chose brachytherapy, 4 chose external beam radiation and 2 chose hormonal ablation (table 4). Four patients chose watchful waiting and another 4 were still undecided about therapy. Mean age in those undergoing radical prostatectomy was 59 years (range 51 to 69) and mean PSA was 6.9 ng/dl (range 3.2 to 12.3). Five of these patients elected surgery at our institution and complete surgical pathology results were available on these patients. The other 2 patients were referred for saturation biopsy and chose to undergo surgery elsewhere. Four patients had Gleason 3⫹4 disease on pathological examination and 1 had Gleason 3⫹3 cancer. All tumors had a volume of 0.5 cc or greater. The saturation biopsy procedure was well tolerated. Only 1 patient had palpitations and shortness of breath when lidocaine was injected. The biopsy procedure was aborted and symptoms resolved without further intervention. Another 2 patients had self-limited lightheadedness and were discharged home. One patient was reevaluated later in the day of biopsy for rectal bleeding, which resolved without intervention. He was treated as an outpatient. DISCUSSION
Since its introduction by Hodge et al,2 random systematic ultrasound guided transrectal prostate biopsy has become
Pt No.—Age
PSA (ng/ml)
Prior PIN
1—52 12.3 No 2—63 5.4 No 3—51 3.7 Yes 4—58 3.2 No 5—69 5 No 6—69 8.9 No 7—52 5.5 No No patient had prior atypia.
Gleason Score
Tumor Vol (cc)
3⫹4 3⫹4 3⫹3 3⫹4 3⫹4 Not available Not available
0.5–2.0 0.5 0.5 0.5–2.0 0.5–2.0 Not available Not available
the mainstay in the diagnosis of prostate cancer. Several studies demonstrated that this sextant technique may miss a substantial percent of cancers and additional sampling of the lateral peripheral zone may increase the diagnostic yield.3–5 There exists a clinically challenging subset of patients who have significant risk factors for prostate cancer despite prior negative biopsies. Extensive or saturation prostate biopsy has diagnosed an additional 30% of cancers in patients with at least 1 negative sextant biopsy.6, 7 This procedure has previously been performed at outpatient surgery centers using general anesthesia, spinal anesthesia or with intravenous sedation. The application of local anesthesia had greatly decreased the pain and discomfort associated with transrectal prostate biopsy.8, 9 Our group reported that saturation biopsy can be performed safely and effectively in the office using local anesthesia.1 Performing saturation biopsy in the office avoids the risks associated with general anesthesia, the costs associated with the operating room and the additional costs of lost work days for the patient and family. Although the specific costs are insurance carrier dependent, the billing department at our institution claims that outpatient surgery saturation biopsies are 4 times more costly than office biopsies. Since our population was one in which many patients underwent 1 or more prior extended biopsy procedures, we believed that our scheme of widely sampling the entire gland, including some traditionally lower yield areas, was important. In our scheme the transition zone was visualized and sampled in medial parasagittal biopsies by advancing the needle through the surgical capsule and sampling the most anterior tissue. The apex was well sampled, including the anterior horn tissue, and the adjacent lateral mid zone and parasagittal mid zone biopsies. In our series parasagittal (medial) biopsies did not provide any additional diagnostic yield and we decreased the total number of parasagittal biopsies from 8 to 4 in the last 36 patients in our cohort.10 We did not routinely perform lesion directed biopsies because a number of studies demonstrated the unreliability of transrectal ultrasound to detect localized prostate cancer.11, 12 We performed saturation prostate biopsy using local anesthesia in the office in 116 consecutive patients who had at least 1 prior negative prostate biopsy and who were at increased risk for prostate cancer. Our overall diagnostic yield was 29%, which is similar to the 30% to 34% yield in other series.6, 7 An important difference is that these other series included patients who had only prior sextant biopsies. However, in our series only 22% of our patients underwent prior sextant biopsies. We noted yields of 31%, 22%, 25% and 30% when 8, 10, 12, or 14 plus cores were taken, respectively. These results show that even these extended biopsy schemes have a significant false-negative rate. We also noted a 64% cancer detection rate (7 of 11) in patients who underwent a single prior sextant biopsy. In this small cohort mean PSA was 8.9 ng/dl, 1 patient has a history of PIN and 3 of the 7 had abnormal DRE. Others described a false-negative rate of up to 50% following a single sextant biopsy.13 We noted the anticipated inverse correlation between the cancer detection rate and the number of prior biopsies (33% with 1 biopsy and 23% with 2 or more). This trend was not
CANCER DETECTION WITH OFFICE SATURATION PROSTATE BIOPSY
seen in the series of Stewart et al, who noted a relatively constant cancer detection rate regardless of the number of prior biopsies.7 They hypothesized that repeat sextant sampling does not adequately sample more remote areas of the gland. However, our cohort included primarily patients who previously had had more widely sampled glands. Some groups criticized that such extensive saturation biopsies would increase the detection of clinically insignificant cancers. Others noted that between 3% and 27% of radical prostatectomy specimen harbor clinically insignificant tumors.14 –16 All patients who chose radical prostatectomy had significant cancers with a Gleason score 6 or 7 and a tumor volume of 0.5 cc or greater. In our series only 9% of cancers diagnosed by saturation biopsy were Gleason score 4 or 5 and, thus, they would be considered insignificant. All of these patients chose watchful waiting as well as 1 with Gleason score 3⫹3 cancer. It appears that in our series the detection of clinically insignificant cancers with saturation biopsy is similar to that in other series in which the diagnosis of prostate cancer was made with fewer biopsy cores. Thus, it does not appear to increase the detection of insignificant cancers. Because of its significant cancer detection rate and minimal morbidity, we propose that office based saturation biopsy should be performed as the next step after initial negative biopsy in a patient with persistent clinical suspicion of prostate cancer. We acknowledge that saturation biopsy is likely to have a false-negative rate because no biopsy scheme can adequately sample the entire prostate gland. However, we believe that this rate is likely to be small compared to less extensive biopsy schemes. We think that the decision to perform another saturation biopsy in this population should be dictated by clinical suspicion, accounting for factors such as family history, race, PSA velocity and physical examination. CONCLUSIONS
Saturation biopsy can be performed safely and effectively in the office using local anesthesia. It has a significant cancer detection rate even in patients who have undergone prior biopsies with more extensive lateral sampling. We believe that office saturation biopsy should be performed after negative initial biopsy in patients with a strong clinical suspicion of prostate cancer. REFERENCES
1. Jones, J. S., Oder, M. and Zippe, C. D.: Saturation prostate biopsy with periprostatic block can be performed in the office. J Urol, 168: 2108, 2002
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2. Hodge, K. K., McNeal, J. E., Terris, M. K. and Stamey, T. A.: Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol, 142: 71, 1989 3. Keetch, D. W., Catalona, W. J. and Smith, D. S.: Serial prostate biopsies in men with persistently elevated serum prostate specific antigen values. J Urol, 151: 1571, 1994 4. Epstein, J. I., Walsh, P. C. and Carter, H. B.: Importance of posterolateral needle biopsies in the detection of prostate cancer. Urology, 57: 1112, 2001 5. Naughton, C. K., Miller, D. C., Mager, D. E., Ornstein, D. K. and Catalona, W. J.: A prospective randomized trial comparing 6 versus 12 prostatic biopsy cores: impact on cancer detection. J Urol, 164: 388, 2000 6. Borboroglu, P. G., Comer, S. W., Riffenburgh, R. H. and Amling, C. L.: Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies. J Urol, 163: 158, 2000 7. Stewart, C. S., Leibovich, B. C., Weaver, A. L. and Lieber, M. M.: Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol, 166: 86, 2001 8. Nash, P. A., Bruce, J. E., Indudhara, R. and Shinohara, K.: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol, 155: 607, 1996 9. Soloway, M. S. and Obek, C.: Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol, 163: 172, 2000 10. Applewhite, J. C., Matagla, B. R. and McCullough, D. L.: Results of the 5 region prostate biopsy method: the repeat biopsy population. J Urol, 168: 500, 2002 11. Epstein, J. I., Walsh, P. C., Carmichael, M. and Brendler, C. B.: Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA, 271: 368, 1994 12. Ellis, W. J., Chetner, M. P., Preston, S. D. and Brawer, M. K.: Diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography. J Urol, 152: 1520, 1994 13. Flanigan, R. C., Catalona, W. J., Richie, J. P., Ahmann, F. R., Hudson, M. A., Scardino, P. T. et al: Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer. J Urol, 152: 1506, 1994 14. Ohori, M., Goad, J. R., Wheeler, T. M., Eastham, J. A., Thompson, T. C. and Scardino, P. T.: Can radical prostatectomy alter the progression of poorly differentiated prostate cancer? J Urol, 152: 1843, 1994 15. Smith, D. S. and Catalona, W. J.: The nature of prostate cancer detected through prostate specific antigen based screening. J Urol, 152: 1732, 1994 16. Patel, A. R., Jones, J. S., Rabets, J., DeOreo, G. and Zippe, C. D.: Parasagittal biopsies add minimal information in repeat saturation prostate biopsy. Urology, 63: 87, 2004
Vol. 172, 94 –97, July 2004 Printed in U.S.A.
DOI: 10.1097/01.ju.0000132134.10470.75
PROSTATE CANCER DETECTION WITH OFFICE BASED SATURATION BIOPSY IN A REPEAT BIOPSY POPULATION JOHN C. RABETS, J. STEPHEN JONES,*,† AMIT PATEL
AND
CRAIG D. ZIPPE‡
From the Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
Purpose: Patients at increased risk for prostate cancer with previously negative biopsies pose a diagnostic challenge. We have previously demonstrated that extensive saturation biopsy can be performed in an office setting. We now report the diagnostic yield of office saturation biopsy in patients at increased risk for prostate cancer and at least 1 negative prior biopsy. Materials and Methods: We performed saturation prostate biopsy with local anesthesia in the office in 116 patients with at least 1 prior negative biopsy and with certain risk factors, namely persistently elevated prostate specific antigen, abnormal digital rectal examination, or prior atypia or PIN on prior biopsy. Results: A total of 34 cancers were detected for an overall diagnostic yield of 29%. A 64% detection rate was noted when a patient had undergone a single prior sextant biopsy. Subgroup analysis revealed a cancer detection rate of 41% when only prior sextant biopsies were performed, and a 24% detection rate when 10 or more cores were taken on prior biopsy. The detection rate was 33% when only 1 prior biopsy was taken and it was 24% when 2 or more prior biopsies were performed. Conclusions: Saturation biopsy can be performed safely and effectively in the office with a significant diagnostic yield even in patients with previous extended biopsy schemes. We believe that it should be the next diagnostic step after an initial negative biopsy in patients in whom the diagnosis of prostate cancer is strongly suspected. KEY WORDS: prostate, prostatic neoplasms, biopsy, ambulatory surgical procedures, ultrasonography
neurovascular bundle. Without delay 24 biopsies were obtained with a spring loaded biopsy gun. The 12 locations on either side were the lateral base (2), lateral mid zone (3), apex (3), parasagittal mid zone (2) and parasagittal base (2) (fig. 1). After analyzing the site specific cancer detection rate using this 24 core saturation biopsy scheme in the first 80 patients we noted that medial parasagittal cores were never positive in the absence of apical, lateral mid zone or lateral base positivity (fig. 2, B). We then changed our biopsy scheme to include only 1 parasagittal mid zone and 1 parasagittal base biopsy from each side, thus, decreasing the total number of cores sampled from 24 to 20 in the last 36 patients.
Random, systematic, ultrasound guided prostate biopsy has vastly improved the ability to diagnose prostate cancer. There exists a challenging cohort of patients with substantial risk factors for prostate cancer who have had previously negative biopsies. For these patients extensive saturation biopsy may be appropriate. However, some urologists are reluctant to perform this procedure, which has been historically performed as an outpatient surgical procedure with anesthesia support. Our group reported that saturation biopsy may be performed safely and with minimal patient discomfort in the urologist office using local anesthesia.1 We now report the diagnostic yield of office saturation biopsy in a repeat biopsy population. METHODS
RESULTS
A total of 116 consecutive patients who were believed to be at increased risk for prostate cancer after at least 1 negative prior biopsy were chosen to undergo office saturation biopsy. Indications were prior PIN or atypia on previous biopsies, prostate specific antigen (PSA) persistently greater than 2.5 ng/dl or an abnormal digital rectal examination (DRE). After obtaining informed consent saturation biopsy with local anesthesia was performed, as described previously.1 Briefly, the patient was placed in the left lateral decubitus position and the ultrasound probe was placed transrectally. A 22 gauge spinal needle was passed through the biopsy guide channel and 10 cc 1% lidocaine was injected into each
A total of 116 consecutive patients underwent saturation biopsy between February 2002 and September 2003. Table 1 lists patient characteristics. Mean age in this cohort was 62 years (range 47 to 83) and mean PSA was 9.2 ng/dl (range 1.7 to 48.6). All patients had localized disease on clinical examination. The mean number of prior biopsies was 1.7 (range 1 to 7). The indication for repeat biopsy was PIN in 33% of cases or atypia in 8% on prior biopsy, abnormal DRE in 12% and increased PSA (greater than 2.5 ng/dl) in 47%. Adenocarcinoma was diagnosed in 34 patients for an overall diagnostic yield of 29%. Cancer was detected in 23 of 70 patients (33%) with only 1, 7 of 28 (25%) with 2 and 4 of 18 (22%) with 3 or more prior biopsies (table 2). Complete information regarding the number of cores taken in the 70 patients who had only a single prior biopsy session was available on 59. Cancer was detected in 7 of the 11 patients (64%) who only had a single prior sextant biopsy. Mean PSA in this group of 7 patients diagnosed with cancer was 8.9 ng/dl (range 2.4 to 21.7). One of the 7 patients had PIN on prior biopsy and 3 had abnormal DRE.
Accepted for publication February 13, 2004. * Correspondence: 9500 Euclid Ave., Suite A100, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195 (telephone: 216-839-3666; FAX: 216-839-3660; e-mail: [email protected]). † Financial interest and/or other relationship with Pfizer, Abbott and Cook. ‡ Financial interest and/or other relationship with Pfizer, AstraZeneca and TAP. 94
95
CANCER DETECTION WITH OFFICE SATURATION PROSTATE BIOPSY
TABLE 1. Demographic information and indications in patients undergoing saturation biopsy
FIG. 1. Number and locations of cores sampled for saturation biopsy.
The cancer detection rate was 21% (3 of 14) and 11% (3 of 27) when patients underwent a single 8 and 10 core biopsy session, respectively. Three of the 7 patients who had a single biopsy session in which 12 or more cores were obtained were diagnosed with cancer. Complete records regarding the total number of cores taken per previous biopsy were available on 97 patients (table 2). Of our patients 78% had previous biopsy sessions in which more than 6 cores were obtained. Cancer was detected in 9 of 22 patients (41%) with only prior sextant biopsies (1 or more prior biopsy sessions), in 5 of 16 (31%) with prior 8 core biopsies, in 9 of 41 (22%) with prior 10 core biopsies, in 2 of 8 (25%) with 12 core biopsies and in 3 of 10 (30%) with prior 14 plus core biopsies. In the group diagnosed with cancer after 14 or more cores were taken at prior biopsy sessions mean PSA was 12.2 ng/dl (range 8.9 to 16.7). The mean number of prior biopsies was 2.7 (range 1 to 5). Two patients had a history of PIN and none had abnormal DRE. All 3 patients underwent saturation biopsy within 3 years of the most recent biopsy. Two patients were diagnosed with Gleason score 3⫹3 cancer and 1 had Gleason score 5⫹4 cancer.
No. pts Mean age (range) Mean ng/dl PSA (range) Mean No. prior biopsies (range) No. saturation biopsy indication (%): Prior biopsy PIN Prior biopsy atypia Abnormal DRE Increased PSA No. prior biopsy sessions (%): 1 2 3⫹ No. prior biopsy cores (%): 6 8 10 12 14⫹ No. cores sampled in pts with 1 prior biopsy session (%): 6 8 10 12 14⫹
116 62 (47–83) 9.2 (1.7–48.6) 1.7 (1–7) 116 38 (33) 9 (8) 14 (12) 55 (47) 116 70 (60) 28 (24) 18 (16) 97 22 (23) 16 (17) 41 (42) 8 (8) 10 (10) 59 11 14 27 3 4
(19) (24) (46) (5) (7)
Table 2 shows the cancer yield by indication and PSA. Seven of 38 patients (18%) with a history of PIN had cancer, while cancer was detected in 1 of 9 (11%) with a history of atypia, 5 of 14 (36%) with abnormal DRE and 21 of 55 (38%) whose only indication for repeat biopsy was increased PSA. The cancer detection rate was 20%, 25%, 38% and 50% in patients with PSA less than 2.5, between 2.5 and 10, between 10 and 20, and greater than 20 ng/dl, respectively. Figure 2 shows the location of positive cores. A total of 21 patients were diagnosed with prostate cancer using the initial 24 core biopsy scheme. Figure 2, A shows the locations of biopsy positivity. Of the patients 13 were diagnosed with cancer using the subsequent 20 core scheme. Figure 2, B shows the positivity of exclusively lateral (including apical, lateral mid zone and lateral base biopsies), exclusively medial (including parasagittal mid and parasagittal base) or lateral and medial biopsy positivity. There were no positive parasagittal (medial) cores in the absence of lateral core positivity. In the 34 patients in whom cancer was diagnosed mean age was 65.2 years and mean PSA was 9.9 ng/dl (table 3). Gleason score 6 and 7 cancer was noted in 23 (68%) and 7
FIG. 2. A, location of positive cores in 21 patients diagnosed with cancer who underwent original 24 core biopsy scheme. B, location of biopsy positivity in all 34 patients. Apical, lateral base and lateral mid zone were considered lateral and parasagittal biopsies were considered medial. There were no exclusively positive medial cores.
96
CANCER DETECTION WITH OFFICE SATURATION PROSTATE BIOPSY TABLE 2. Cancer detection rates
TABLE 4. Prostatectomy specimen characteristics
No. pts No. Ca detected (%) No. Ca detection/No. prior biopsy sessions/total No. (%): 1 2 3⫹ No. Ca detection/No. cores sampled on prior biopsy/total No. (%): 6 8 10 12 14⫹ No. Ca detection/No. cores sampled in pts with 1 prior biopsy session/total No. (%): 6 8 10 12 14⫹ No. indication Ca detection/total No. (%): Prior biopsy PIN Prior biopsy atypia Abnormal DRE Elevated PSA No. ng/ml PSA Ca detection/total No. (%): 0–2.5 2.5–10 10–20 Greater than 20
116 34 (29) 23/70 (33) 7/28 (25) 4/18 (22) 97 9/22 (41) 5/16 (31) 9/41 (22) 2/8 (25) 3/10 (30) 59 7/11 (64) 3/14 (21) 3/27 (11) 2/3 (66) 1/4 (25) 7/38 (18) 1/9 (11) 5/14 (36) 21/55 (38) 1/5 (20) 20/79 (25) 10/26 (38) 3/6 (50)
TABLE 3. Diagnosed cancers and treatments chosen No. Ca diagnosed Mean age (range) Mean PSA (range) No. Gleason score (%): 4 5 6 7 8 9 No. treatment (%): Radical prostatectomy External beam radiation Brachytherapy Hormonal ablation Watchful waiting Undecided
34 65 (51–80) 9.9 (2.4–23.4) 2 1 23 7 0 1
(6) (3) (68) (21)
7 4 13 2 4 4
(20) (12) (38) (6) (12) (12)
(3)
patients (21%), respectively, while 3 had a Gleason score of 4 or 5 and 1 had a Gleason score of 9. Seven patients elected radical prostatectomy, 13 chose brachytherapy, 4 chose external beam radiation and 2 chose hormonal ablation (table 4). Four patients chose watchful waiting and another 4 were still undecided about therapy. Mean age in those undergoing radical prostatectomy was 59 years (range 51 to 69) and mean PSA was 6.9 ng/dl (range 3.2 to 12.3). Five of these patients elected surgery at our institution and complete surgical pathology results were available on these patients. The other 2 patients were referred for saturation biopsy and chose to undergo surgery elsewhere. Four patients had Gleason 3⫹4 disease on pathological examination and 1 had Gleason 3⫹3 cancer. All tumors had a volume of 0.5 cc or greater. The saturation biopsy procedure was well tolerated. Only 1 patient had palpitations and shortness of breath when lidocaine was injected. The biopsy procedure was aborted and symptoms resolved without further intervention. Another 2 patients had self-limited lightheadedness and were discharged home. One patient was reevaluated later in the day of biopsy for rectal bleeding, which resolved without intervention. He was treated as an outpatient. DISCUSSION
Since its introduction by Hodge et al,2 random systematic ultrasound guided transrectal prostate biopsy has become
Pt No.—Age
PSA (ng/ml)
Prior PIN
1—52 12.3 No 2—63 5.4 No 3—51 3.7 Yes 4—58 3.2 No 5—69 5 No 6—69 8.9 No 7—52 5.5 No No patient had prior atypia.
Gleason Score
Tumor Vol (cc)
3⫹4 3⫹4 3⫹3 3⫹4 3⫹4 Not available Not available
0.5–2.0 0.5 0.5 0.5–2.0 0.5–2.0 Not available Not available
the mainstay in the diagnosis of prostate cancer. Several studies demonstrated that this sextant technique may miss a substantial percent of cancers and additional sampling of the lateral peripheral zone may increase the diagnostic yield.3–5 There exists a clinically challenging subset of patients who have significant risk factors for prostate cancer despite prior negative biopsies. Extensive or saturation prostate biopsy has diagnosed an additional 30% of cancers in patients with at least 1 negative sextant biopsy.6, 7 This procedure has previously been performed at outpatient surgery centers using general anesthesia, spinal anesthesia or with intravenous sedation. The application of local anesthesia had greatly decreased the pain and discomfort associated with transrectal prostate biopsy.8, 9 Our group reported that saturation biopsy can be performed safely and effectively in the office using local anesthesia.1 Performing saturation biopsy in the office avoids the risks associated with general anesthesia, the costs associated with the operating room and the additional costs of lost work days for the patient and family. Although the specific costs are insurance carrier dependent, the billing department at our institution claims that outpatient surgery saturation biopsies are 4 times more costly than office biopsies. Since our population was one in which many patients underwent 1 or more prior extended biopsy procedures, we believed that our scheme of widely sampling the entire gland, including some traditionally lower yield areas, was important. In our scheme the transition zone was visualized and sampled in medial parasagittal biopsies by advancing the needle through the surgical capsule and sampling the most anterior tissue. The apex was well sampled, including the anterior horn tissue, and the adjacent lateral mid zone and parasagittal mid zone biopsies. In our series parasagittal (medial) biopsies did not provide any additional diagnostic yield and we decreased the total number of parasagittal biopsies from 8 to 4 in the last 36 patients in our cohort.10 We did not routinely perform lesion directed biopsies because a number of studies demonstrated the unreliability of transrectal ultrasound to detect localized prostate cancer.11, 12 We performed saturation prostate biopsy using local anesthesia in the office in 116 consecutive patients who had at least 1 prior negative prostate biopsy and who were at increased risk for prostate cancer. Our overall diagnostic yield was 29%, which is similar to the 30% to 34% yield in other series.6, 7 An important difference is that these other series included patients who had only prior sextant biopsies. However, in our series only 22% of our patients underwent prior sextant biopsies. We noted yields of 31%, 22%, 25% and 30% when 8, 10, 12, or 14 plus cores were taken, respectively. These results show that even these extended biopsy schemes have a significant false-negative rate. We also noted a 64% cancer detection rate (7 of 11) in patients who underwent a single prior sextant biopsy. In this small cohort mean PSA was 8.9 ng/dl, 1 patient has a history of PIN and 3 of the 7 had abnormal DRE. Others described a false-negative rate of up to 50% following a single sextant biopsy.13 We noted the anticipated inverse correlation between the cancer detection rate and the number of prior biopsies (33% with 1 biopsy and 23% with 2 or more). This trend was not
CANCER DETECTION WITH OFFICE SATURATION PROSTATE BIOPSY
seen in the series of Stewart et al, who noted a relatively constant cancer detection rate regardless of the number of prior biopsies.7 They hypothesized that repeat sextant sampling does not adequately sample more remote areas of the gland. However, our cohort included primarily patients who previously had had more widely sampled glands. Some groups criticized that such extensive saturation biopsies would increase the detection of clinically insignificant cancers. Others noted that between 3% and 27% of radical prostatectomy specimen harbor clinically insignificant tumors.14 –16 All patients who chose radical prostatectomy had significant cancers with a Gleason score 6 or 7 and a tumor volume of 0.5 cc or greater. In our series only 9% of cancers diagnosed by saturation biopsy were Gleason score 4 or 5 and, thus, they would be considered insignificant. All of these patients chose watchful waiting as well as 1 with Gleason score 3⫹3 cancer. It appears that in our series the detection of clinically insignificant cancers with saturation biopsy is similar to that in other series in which the diagnosis of prostate cancer was made with fewer biopsy cores. Thus, it does not appear to increase the detection of insignificant cancers. Because of its significant cancer detection rate and minimal morbidity, we propose that office based saturation biopsy should be performed as the next step after initial negative biopsy in a patient with persistent clinical suspicion of prostate cancer. We acknowledge that saturation biopsy is likely to have a false-negative rate because no biopsy scheme can adequately sample the entire prostate gland. However, we believe that this rate is likely to be small compared to less extensive biopsy schemes. We think that the decision to perform another saturation biopsy in this population should be dictated by clinical suspicion, accounting for factors such as family history, race, PSA velocity and physical examination. CONCLUSIONS
Saturation biopsy can be performed safely and effectively in the office using local anesthesia. It has a significant cancer detection rate even in patients who have undergone prior biopsies with more extensive lateral sampling. We believe that office saturation biopsy should be performed after negative initial biopsy in patients with a strong clinical suspicion of prostate cancer. REFERENCES
1. Jones, J. S., Oder, M. and Zippe, C. D.: Saturation prostate biopsy with periprostatic block can be performed in the office. J Urol, 168: 2108, 2002
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2. Hodge, K. K., McNeal, J. E., Terris, M. K. and Stamey, T. A.: Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol, 142: 71, 1989 3. Keetch, D. W., Catalona, W. J. and Smith, D. S.: Serial prostate biopsies in men with persistently elevated serum prostate specific antigen values. J Urol, 151: 1571, 1994 4. Epstein, J. I., Walsh, P. C. and Carter, H. B.: Importance of posterolateral needle biopsies in the detection of prostate cancer. Urology, 57: 1112, 2001 5. Naughton, C. K., Miller, D. C., Mager, D. E., Ornstein, D. K. and Catalona, W. J.: A prospective randomized trial comparing 6 versus 12 prostatic biopsy cores: impact on cancer detection. J Urol, 164: 388, 2000 6. Borboroglu, P. G., Comer, S. W., Riffenburgh, R. H. and Amling, C. L.: Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies. J Urol, 163: 158, 2000 7. Stewart, C. S., Leibovich, B. C., Weaver, A. L. and Lieber, M. M.: Prostate cancer diagnosis using a saturation needle biopsy technique after previous negative sextant biopsies. J Urol, 166: 86, 2001 8. Nash, P. A., Bruce, J. E., Indudhara, R. and Shinohara, K.: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol, 155: 607, 1996 9. Soloway, M. S. and Obek, C.: Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol, 163: 172, 2000 10. Applewhite, J. C., Matagla, B. R. and McCullough, D. L.: Results of the 5 region prostate biopsy method: the repeat biopsy population. J Urol, 168: 500, 2002 11. Epstein, J. I., Walsh, P. C., Carmichael, M. and Brendler, C. B.: Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA, 271: 368, 1994 12. Ellis, W. J., Chetner, M. P., Preston, S. D. and Brawer, M. K.: Diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography. J Urol, 152: 1520, 1994 13. Flanigan, R. C., Catalona, W. J., Richie, J. P., Ahmann, F. R., Hudson, M. A., Scardino, P. T. et al: Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer. J Urol, 152: 1506, 1994 14. Ohori, M., Goad, J. R., Wheeler, T. M., Eastham, J. A., Thompson, T. C. and Scardino, P. T.: Can radical prostatectomy alter the progression of poorly differentiated prostate cancer? J Urol, 152: 1843, 1994 15. Smith, D. S. and Catalona, W. J.: The nature of prostate cancer detected through prostate specific antigen based screening. J Urol, 152: 1732, 1994 16. Patel, A. R., Jones, J. S., Rabets, J., DeOreo, G. and Zippe, C. D.: Parasagittal biopsies add minimal information in repeat saturation prostate biopsy. Urology, 63: 87, 2004