- Email: [email protected]
Prostate Cancers Diagnosed at Repeat Biopsy are Smaller and Less Likely to be High Grade
Prostate Cancers Diagnosed at Repeat Biopsy are Smaller and Less Likely to be High Grade Nelly Tan,* Brian R. Lane, Jianbo Li, Ayman S. Moussa, Meghan Soriano and J. Stephen Jones† From the Glickman Urologic and Kidney Institute, Cleveland Clinic (NT), Cleveland, Ohio, and Thomas Haider Biomedical Sciences Program, University of California-Riverside/University of California-Los Angeles, Riverside, California
Purpose: We investigated whether prostate cancer diagnosed on initial prostate biopsy had worse pathological outcomes compared to that diagnosed on repeat prostate biopsy. Materials and Methods: We reviewed 905 newly diagnosed prostate cancer cases from 2000 to 2007. Patients were stratified by the number of previous biopsies, including the initial biopsy in 690, and 1 and 2 or greater negative previous biopsies in 142 and 73, respectively. We analyzed Gleason sum, number of cores taken, percent of positive cores and bilaterality of prostate cancer. Clinically insignificant cancers were defined according to prostate specific antigen density 0.4 ng/ml or less, 3 or fewer positive cores, 50% or less of maximum cancer in any core and Gleason sum 6 or less. Results: Prostate cancer was diagnosed in 57%, 23% and 21% of cases in the initial, and 1 and 2 or greater negative previous biopsies groups, respectively. Initial prostate biopsy showed a higher number and percent of positive cores, and the maximum percent of prostate cancer involved in a core. However, the Gleason pattern distribution differed significantly in the 3 groups with the highest percent (14%) of Gleason sum 8 or greater in the subset with 2 or greater negative previous biopsies (p ⬍0.01). On multivariate analysis accounting for prostate specific antigen, digital rectal examination, age and biopsy schema the number of previous biopsies was an independent predictor of the number and percent of positive cores, maximum prostate cancer involved in a core, and bilaterality (p ⬍0.01). Only prostate specific antigen, digital rectal examination and age but not the number of previous biopsies independently predicted Gleason sum (p ⬍0.01). Conclusions: Prostate cancer diagnosed on initial prostate biopsy had higher volume. However, there were a significant number of high grade prostate cancers detected on the third or greater prostate biopsy, underscoring the importance of repeat prostate biopsy in the setting of increased or increasing prostate specific antigen despite negative previous prostate biopsy. Key Words: prostate, prostatic neoplasms, biopsy, prostate-specific antigen
rostate biopsy is indicated in the evaluation of men with increased PSA and/or abnormal DRE. Repeat PB is usually performed in men not found to have PC on the initial PB but with persistently increased or increasing PSA, PSA velocity greater than 0.75 ng/ml yearly, low free PSA, abnormal DRE or initial pathological finding related to an increased risk of cancer, such as high grade premalignant intraepithelial neoplasia or atypia.1–5 Previous studies have shown that on repeat PB patients are more likely to have indolent cancer3,6 – 8 and a more favorable prognosis. Moreover, some questions have arisen about whether repeat biopsy is justified after multiple negative biopsies in older men,9 especially since PB is not without risk and the likelihood of detecting clinically insignificant cancer is high.6,7 However, to our knowledge the pathological differences on initial vs repeat PB have not been previously reported in the literature. We investigated whether patients who undergo repeat PB in the face of prior
P
Submitted for publication January 28, 2008. Study received institutional review board approval. * Correspondence: Thomas Haider Biomedical Sciences Program, University of California-Riverside/University of California-Los Angeles, Riverside, California (e-mail: [email protected]). † Financial interest and/or other relationship with Pfizer, Cook, Abbott and Endocare.
0022-5347/08/1804-1325/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
negative biopsies have more favorable pathological outcomes in the biopsy specimens. MATERIALS AND METHODS Patient Characteristics We retrospectively reviewed the records of 2,309 patients in an institutional review board approved PB database who underwent PB positive for PC from 2000 to 2007 at Cleveland Clinic. Of the 2,309 patients 131 (5.7%) were excluded from study because of incomplete pathological data or a history of PC managed by prior radiotherapy, cryotherapy or hormonal therapy or active surveillance. Of the remaining 2,178 patients 905 (41.6%) had a new diagnosis of PC and were evaluated for clinical and biopsy pathological information, including primary and secondary GG, number of cores taken, number of cores positive for PC, percent maximum cancer in any given core and bilaterality. TRUS guided biopsy was performed with an 18 gauge needle biopsy gun after periprostatic nerve block beginning in 2001 and without periprostatic block before that time. Clinical and Pathological Analysis The clinical variables collected were patient age, race, serum PSA, biopsy GS, prostate volume, DRE, NuPB performed and biopsy schema with standard defined as fewer than 20
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Vol. 180, 1325-1329, October 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.06.022
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PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER TABLE 1. Clinical characteristics of 905 patients with newly diagnosed PC stratified by NegPBs No. NegPBs Factor
Mean ⫾ SD age No. black/total No. (%) No. median ng/ml PSA (IQR) No. abnormal DRE/total No. (%) No. biopsy schema/total No. (%): Standard (less than 20) Saturation (20 or greater) No. clinical stage T1c/total No. (%) Median cm3 prostate vol (IQR)
Initial Biopsy 66.7 ⫾ 9.3 82/690 (11.9) 6.2 (4.6–9.7) 78/675 (11.6) 558/683 125/683 597/675 40
(81.7) (18.3) (88.4) (25–48)
1
2 or Greater
65.5 ⫾ 8.6 12/142 (8.5) 6.4 (4.6–8.7) 13/139 (9.4) 58/142 84/142 126/139 42
66.7 ⫾ 7.5 6/73 (8.2) 10.7 (8.2–19.9) 5/71 (7.0)
(40.8) (59.2) (90.6) (26–55)
20/72 52/72 66/71 50
(27.8) (72.2) (93.0) (30–70)
p Value 0.36 0.36 0.41 0.42 ⬍0.01 0.42 ⬍0.01
Eight and 20 patients had missing information on biopsy schema and clinical stage T1c, respectively.
cores and saturation defined as 20 cores or greater. Prostate volume was measured by TRUS and by surgical prostatectomy specimen weight when unavailable, which was necessary in 20% of the patients. Biopsy specimens were reviewed by a genitourinary pathologist according to a previously described protocol, including primary and secondary Gleason scores.10 Clinically insignificant cancer was defined as PC fulfilling the Epstein criteria, including in 47 patients who satisfied all 4 available criteria (PSA density 0.4 ng/ml or less, 3 or fewer positive cores, 50% or less of maximum cancer in any core and GS 6 or less).11 Statistical Analysis The pathological outcome variables examined were GS, number of positive cores, maximum percent of cancer in any given core, bilaterality and clinically insignificant cancer. Patient demographics and clinical measures were used as covariates in the analysis. On univariate analysis Pearson’s chi-square test was used for comparisons of categorical variables and the t test or 1-way ANOVA was used for continuous variables. Percents or proportions are reported for categorical variables, and the medians and IQR are shown for continuous variables. Multivariate regression or logistic regression analysis was used to assess the relationship between outcome pathological features, including GS, number of positive cores, percent of positive core, maximum percent of cancer, bilaterality, clinically insignificant cancer and number of previous biopsies adjusted by patient demographic and clinical variables, such as age, DRE, PSA,
biopsy and prostate volume. All results were considered significant at ␣ ⫽ 0.05. Analyses were performed using the R statistical software package (Department of Statistics and Mathematics, Wirtschaftsuniversität Wien, Vienna, Austria). RESULTS A new PC diagnosis was made in 905 of the 2,178 biopsies performed (41.6%). PC was detected in 690 of 1,212 patients (56.9%) at initial biopsy, in 142 of 621 (22.9%) with 1 NegPB and in 73 of 345 (21.2%) with 2 or greater NegPBs. Table 1 lists the clinical characteristics of 905 patients with clinically localized PC stratified according to the number of PBs. There was no difference in patient age, race, serum PSA, DRE and clinical stage between initial and repeat biopsies. There was a statistically significant difference in biopsy schema (standard vs saturation), and between the initial and 1 NegPB compared to 2 or greater NegPBs (p ⬍0.01). A standard biopsy schema of fewer than 20 cores was used in 558 of 690 (80.9%), 58 of 142 (40.8%) and 20 of 73 cases (27.4%) in the initial PB, 1 NegPB and 2 or greater NegPBs groups (p ⬍0.01). Prostate volume increased with NuPB with a mean prostate volume of 40, 42 and 54 cm3 in the initial PB, 1 NegPB and 2 or greater NegPB groups (p ⬍0.01). Table 2 shows univariate analysis of clinical outcomes in patients according to NuPB. In the 3 groups the incidence of GS 5-6 in the first, second and third or greater PB was 358 of 690 (51.9%), 97 of 142 (68.3%) and 45 of 73 (61.6%),
TABLE 2. Needle biopsy pathological outcomes in 905 patients with newly diagnosed PC stratified by number of NegPBs NegPBs Factor No. pts No. GS (%): 5–6 3⫹4 4⫹3 8–10 Median cores (IQR): No. taken No. pos % Pos Max % involved (IQR) No. bilat/total No. (%) No. clinically insignificant Ca/total No. (%)
Initial Biopsy 689 358 150 96 85
1
2 or Greater
139 (52.0) (21.8) (13.9) (12.3)
12 (10–13) 3 (2–6) 25 (13–50) 30 (10–70) 291/680 (42.8) 37/480 (7.7)
97 19 12 11
73 (69.8) (13.7) (8.6) (7.9)
20 (11–20) 2 (1–5) 15 (10–25) 15 (5–50) 40/141 (28.4) 6/86 (7.0)
45 13 5 10
⬍0.01 (61.6) (17.8) (6.8) (13.7)
20 (12–20) 2 (1–3.5) 10 (5–25) 14 (5–40) 18/73 (24.7) 4/49 (8.2)
Four, 11 and 209 patients had missing information on GS, bilateral PC and clinically insignificant cancer, respectively.
p Value
⬍0.01
⬍0.01 ⬍0.01 0.96
PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER respectively (p ⬍0.01). PC was more likely to be GS 7 or greater on initial biopsy compared to repeat biopsy (331 of 690 cases or 48.0% vs 70 of 215 or 32.6%, p ⬍0.01). However, the incidence of GS 8 –10 cancer was 10 of 73 cases (13.7%) in the group with 2 or greater NegPBs compared with 85 of 690 (12.3%) and 11 of 142 (7.7%) in the initial PB and 1 NegPB groups, respectively (p ⫽ 0.26). As expected due to the preferential use of the saturation technique for repeat biopsies, the median number of cores was higher on repeat biopsy compared with that on initial biopsy (20 vs 12, p ⬍0.01). Despite this fact the mean number of cores with PC was 4.3, 3.4 and 3.0 in the initial PB, 1 NegPB and 2 or greater NegPBs groups, respectively (p ⬍0.01). There was an even more notable difference in the percent of cores positive for cancer (34.4%, 21.5% and 18.3%, respectively, p ⬍0.01). Additionally, the maximum percent of cancer in any given core was highest on initial biopsy compared to that on 1 NegPB and 2 or greater NegPBs (41% vs 29% and 27%, respectively, p ⬍0.01). PC was bilateral in 43% of cases on initial biopsy, in 28% on 1 NegPB and in 25% on 2 or greater NegPBs (p ⬍0.01). Finally, there was no difference in the rate of clinically insignificant cancer, as defined by the Epstein criteria,13 among the 3 groups, that is 7.7%, 7.0% and 8.2% in the initial PB, 1 NegPB and 2 or greater NegPB groups, respectively (p ⫽ 0.96). On multivariate linear regression analysis NuPB was an independent predictor of several pathological outcomes, including number of positive cores, percent of cores with PC, maximum involvement of a core with PC and bilaterality (p ⬍0.01, table 3). Of note, although age, PSA and DRE were significant predictors of GS, NuPB was not an independent predictor of this pathological outcome. Biopsy schema (standard vs saturation) predicted the number of positive cores (p ⬍0.01). However, biopsy schema predicted a lower percent of positive cores (p ⬍0.01).
DISCUSSION In our study PC was diagnosed in 57% of patients undergoing initial biopsy, 23% of those undergoing second biopsy and 21% undergoing third or greater biopsies. In comparison, in the prospective European Prostate Cancer Detection study Djavan et al performed PB in patients with PSA between 4 and 10 ng/ml, and found a PC detection rate of 24% and 13% for the first and second biopsies, respectively.7 We believe that the PC detection rates in the series of Djavan et al are lower compared to our findings likely due to the explanations provided and they are primarily related to their use of the sextant schema, which predominated in clinical practice at the time of their report. We found that the incidences of intermediate and high grade PC (GS 7 or greater) was 48%, 30% and 38% on initial PB, 1 NegPB and 2 or greater NegPBs, respectively. Other studies have shown the potential to detect high grade PC on repeat biopsies after negative prior biopsies. Djavan et al evaluated PC detection on biopsies 1 to 3 in patients with PSA 4 to 10 ng/ml and noted a mean of 31.1%, 29.8% and 8.2% GG 4/5 disease, respectively. Our study showed a higher percent of GG 4/5, including 48% on initial PB, 30.2% on 1 NegPB and 38.3% on 2 or greater NegPBs. In our study the percent of GS 8-10 was highest in the 2 NegPBs group vs
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TABLE 3. Predictors of clinical outcomes on multivariate analysis Clinical Variable Gleason score: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age No. pos cores: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age % Pos core: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age Max % Ca: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age Bilat: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age Epstein clinically insignificant Ca: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age
Coefficient
p Value
⫺0.0741 ⫺0.1293
0.253 0.125
0.0003 0.5079 0.0325
0.010 ⬍0.01 ⬍0.01
⫺0.8536 0.8321
⬍0.01 0.022
⫺0.0001 0.9886 0.0320
0.825 0.048 0.066
⫺4.9308 ⫺12.0219
⬍0.01 ⬍0.01
⫺0.0020 12.7257 0.2121
0.622 ⬍0.01 0.033
⫺8.2716 0.2084
⬍0.01 0.938
0.0025 13.6917 0.4125
0.525 ⬍0.01 ⬍0.01
⫺0.4612 ⫺0.0382
⬍0.01 0.829
0.0001 0.1803 0.0239
0.760 0.459 0.003
0.0470 0.0597
0.864 0.869
0.0004 1.0674 ⫺0.076
0.465 0.019 ⬍0.01
the initial PB and 1 NegPB groups (14% vs 12% and 8%, respectively). The lower PC detection rates and GG 4/5 incidence in the study of Djavan et al may be explained by the practice pattern and biopsy technique, which also differed from ours based on their practice of recommending repeat biopsies automatically 6 to 8 weeks after an initial negative biopsy. However, we performed repeat biopsy based on clinical suspicion according to the factors described. Moreover, Djavan et al performed standard sextant biopsy with 2 additional transition zone biopsies. Routine transition zone biopsies have not been shown to contribute significantly more information and they are not currently recommended.12 Notably Haas et al found that sextant biopsy missed most tumors in a recent autopsy series,12 providing further evidence that sextant biopsy has a high false-negative detection rate. Although the PC detection rate decreased with increasing negative PB, our study shows that a significant percent of high grade cancer still remains at the third or greater biopsy. Consistent with our data, Epstein et al studied radical prostatectomy specimens and found 12% positive surgical margin and 27% nonorgan confined PC rates in patients diagnosed with PC after benign initial biopsies.6 These findings indicate that prior benign biopsies in men subsequently diagnosed with PC do not define indolent tumor. Prior studies demonstrate improved cancer detection with saturation biopsy on repeat biopsy.13,14 Cancer detec-
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PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER
tion rates between 13.5% and 44% have been reported with saturation biopsy in patients undergoing rebiopsy.13 On our multivariate analysis biopsy schema predicted the number of positive cores and the percent of positive cores on PB. As the number of cores taken increased, patients were likely to have a higher number of positive cores with a lower overall percent of positive cores. We believe that these data show that the extent of cancer is better defined in this setting by taking more cores. Although our univariate analysis suggested that PC on initial biopsy was more likely to be GS 7 or greater compared to PC diagnosed on a second biopsy, on our multivariate analysis NuPB was not an independent predictor of GS. Only PSA, DRE and age were independent predictors of GS on biopsy. In 2004 Stamey et al reported that PSA no longer correlates with the percent of GG 4/5 and it correlates only weakly with cancer volume, leading them to conclude that PSA is useful only as a marker of benign prostatic hyperplasia.15 Recent studies suggest that preoperative PSA is still predictive of cancer volume,16,17 grade16 and indolent cancer.18 Also, it is important to understand that Stamey et al drew their conclusions that PSA correlated poorly with GS and tumor volume from a highly select population of patients who underwent radical prostatectomy,15 overlooking the fact that only a small percent of men, even if diagnosed with PC, undergo this operation. In the current study PSA predicted GS on subsequent biopsies and age was an independent predictor of GS and tumor volume on multivariate analysis. Thus, as Hong et al pointed out, the relationship of PSA to cancer status in patients with known cancer may be limited but in an overall screening or biopsy population there remains a close link of PSA and cancer risk.19 Although prior studies have shown that cancer identified on repeat biopsy is typically lower volume and carries less risk than cancer found during the initial prostate biopsy,3,6,7 to our knowledge our study is the first to consider biopsy pathological outcomes in the extended biopsy era and our multivariate analysis revealed that NuPB is an important predictor of biopsy pathological outcomes. Patients with prior negative biopsies are more likely to have lower volume cancer and less likely have bilateral cancer. Nevertheless, our findings suggest that these patients are still at significant, if not increased, risk for high grade, localized cancer in the highly selective setting of repeat biopsy for persistently suspicious findings following prior NegPBs. The clinical implication of diligent followup in this setting is that these tumors may be significant and have a higher likelihood of cure based on size. Thus, detection may be particularly important in the setting of persistently increased or increasing PSA following negative biopsy, especially if only a single prior sextant biopsy was performed. To our knowledge our study is the first to evaluate all patients with PC diagnosed on biopsy irrespective of final management. Thus, our findings reflect the real-life situation that urologists face prospectively when reviewing various management options with patients. The most significant limitations of this study are its retrospective nature, and lack of pathological and prognostic outcomes. In addition, biopsies were performed by different urologists and, thus, there is likely to have been some variations in the indications for biopsy and in the exact techniques used for biopsy and prostate volume measurement. Moreover, there is a
limited correlation between TRUS volume and surgical specimen weight for 20% of the prostate volumes measured (r ⫽ 0.70).20 Furthermore, the proportion of biopsies using the saturation technique was likely based on the referral nature of our practice. Many such patients are referred for saturation biopsy in the office after 1 or more negative biopsies when there is persistent suspicion of cancer. Thus, the rate of saturation biopsy is higher than in most current reports, so that our detection rate may be higher than would have been predicted using less aggressive biopsy schemes. CONCLUSIONS Given that PB is not without risk or inconvenience, the indications for repeat biopsy after 1 or more negative PBs have not been clearly defined and actual clinical practice has varied greatly. We found that 38% of cancers diagnosed after 2 or more NegPBs were intermediate or high grade (GS 7 or greater), including 14% that were GS 8-10. Thus, although multiple negative prior biopsies may portend improved pathological outcomes, a significant number of patients have aggressive high risk cancers despite negative previous evaluation. Although cancers found at repeat biopsy are smaller and other pathological features are in general more encouraging, it appears justified to consider repeat biopsy if concerning clinical or prior biopsy findings exist.
Abbreviations and Acronyms DRE GG GS NegPB NuPB PB PC PSA TRUS
⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽
digital rectal examination Gleason grade Gleason sum negative previous biopsy number of previous biopsies prostate biopsy prostate cancer prostate specific antigen transrectal ultrasound
REFERENCES 1.
Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R et al: Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 1992; 267: 2215. 2. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A et al: Use of the percentage of free prostatespecific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 1998; 279: 1542. 3. Lopez-Corona E, Ohori M, Wheeler TM, Reuter VE, Scardino PT, Kattan MW et al: Prostate cancer diagnosed after repeat biopsies have a favorable pathological outcome but similar recurrence rate. J Urol 2006; 175: 923. 4. Park S, Shinohara K, Grossfeld GD and Carroll PR: Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy. J Urol 2001; 165: 1409. 5. Potter SR, Horniger W, Tinzl M, Bartsch G and Partin AW: Age, prostate-specific antigen, and digital rectal examination as determinants of the probability of having prostate cancer. Urology 2001; 57: 1100. 6. Epstein JI, Walsh PC, Akingba G and Carter HB: The significance of prior benign needle biopsies in men subsequently diagnosed with prostate cancer. J Urol 1999; 162: 1649.
PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER 7.
8.
9.
10.
11.
12.
13. 14.
15.
16.
17.
18.
19.
Djavan B, Ravery V, Zlotta A, Dobronski P, Dobrovits M, Fakhari M et al: Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J Urol 2001; 166: 1679. Epstein JI, Walsh PC, Sauvageot J and Carter HB: Use of repeat sextant and transition zone biopsies for assessing extent of prostate cancer. J Urol 1997; 158: 1886. Hoffman RM, Denberg T, Hunt WC and Hamilton AS: Prostate cancer testing following a negative prostate biopsy: over testing the elderly. J Gen Intern Med 2007; 22: 1139. Epstein JI, Allsbrook WC Jr, Amin MB and Egevad LL: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005; 29: 1228. Epstein JI, Walsh PC, Carmichael M and Brendler CB: Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994; 271: 368. Haas GP, Delongchamps NB, Jones RF, Chandan V, Serio AM, Vickers AJ et al: Needle biopsies on autopsy prostates: sensitivity of cancer detection based on true prevalence. J Natl Cancer Inst 2007; 99: 1484. Jones JS: Saturation biopsy for detecting and characterizing prostate cancer. BJU Int 2007; 99: 1340. Jones JS, Patel A, Schoenfield L, Rabets JC, Zippe CD and Magi-Galluzzi C: Saturation technique does not improve cancer detection as an initial prostate biopsy strategy. J Urol 2006; 175: 485. Stamey TA, Caldwell M, McNeal JE, Nolley R, Hemenez M and Downs J: The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004; 172: 1297. Figler BD, Reuther AM, Dhar N, Levin H, Magi-Galluzzi C, Zhou M et al: Preoperative PSA is still predictive of cancer volume and grade in late PSA era. Urology 2007; 70: 711. Ochiai A, Troncoso P and Babaian RJ: The relationship between serum prostate specific antigen level and tumor volume persists in the current era. J Urol 2007; 177: 903. Steyerberg EW, Roobol MJ, Kattan MW, van der Kwast TH, de Koning HJ and Schroder FH: Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol 2007; 177: 107. Hong YM, Lai FC, Chon CH, McNeal JE and Presti JC Jr: Impact of prior biopsy scheme on pathologic features of
20.
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cancers detected on repeat biopsies. Urol Oncol 2004; 22: 7. Sajadi KP, Terris MK, Hamilton RJ, Cullen J, Amling CL, Kane CJ et al: Body mass index, prostate weight and transrectal ultrasound prostate volume accuracy. J Urol 2007; 178: 990.
EDITORIAL COMMENT The decision to repeat PB has many implications, including a risk-benefit assessment. These authors report that in their experience cancer on repeat biopsies is found frequently (21% of cases), is aggressive (GS 7 and 8-10 in 32% and 14%) and is not indolent (7% and 8% on initial and repeat biopsy, respectively). However, patients who undergo rebiopsy had more cores taken, larger prostate glands, and fewer and a lower percent of cores with cancer. Age, PSA and DRE were again found to correlate with pathological features, including GG but the number of previous biopsies was not. They concluded that in cases at continuous suspicion for cancer repeat biopsy detects significant cancer and when using saturation biopsy, over diagnosis is not a concern. It should be emphasized that these results can be related to the high risk nature of their patients (high rate of GS greater than 7), the rebiopsy scheme protocol (high rate of cancer), and the criteria for and timing of rebiopsy (low incidence of indolent cancer). Although factors such as atypia, HGPIN (reference 1 in article), free PSA and PSA kinetics1 were not evaluated, it is clear that if there is a clinical reason to suspect cancer, rebiopsy is certainly appropriate. Ernesto López-Corona Department of Urology Hospital Angeles Tijuana Onco-Urology Service Hospital General de Tijuana Tijuana, Baja California Mexico 1.
Park SJ, Miyake H, Hara I and Eto H: Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy. Int J Urol 2003; 10: 68.
Purpose: We investigated whether prostate cancer diagnosed on initial prostate biopsy had worse pathological outcomes compared to that diagnosed on repeat prostate biopsy. Materials and Methods: We reviewed 905 newly diagnosed prostate cancer cases from 2000 to 2007. Patients were stratified by the number of previous biopsies, including the initial biopsy in 690, and 1 and 2 or greater negative previous biopsies in 142 and 73, respectively. We analyzed Gleason sum, number of cores taken, percent of positive cores and bilaterality of prostate cancer. Clinically insignificant cancers were defined according to prostate specific antigen density 0.4 ng/ml or less, 3 or fewer positive cores, 50% or less of maximum cancer in any core and Gleason sum 6 or less. Results: Prostate cancer was diagnosed in 57%, 23% and 21% of cases in the initial, and 1 and 2 or greater negative previous biopsies groups, respectively. Initial prostate biopsy showed a higher number and percent of positive cores, and the maximum percent of prostate cancer involved in a core. However, the Gleason pattern distribution differed significantly in the 3 groups with the highest percent (14%) of Gleason sum 8 or greater in the subset with 2 or greater negative previous biopsies (p ⬍0.01). On multivariate analysis accounting for prostate specific antigen, digital rectal examination, age and biopsy schema the number of previous biopsies was an independent predictor of the number and percent of positive cores, maximum prostate cancer involved in a core, and bilaterality (p ⬍0.01). Only prostate specific antigen, digital rectal examination and age but not the number of previous biopsies independently predicted Gleason sum (p ⬍0.01). Conclusions: Prostate cancer diagnosed on initial prostate biopsy had higher volume. However, there were a significant number of high grade prostate cancers detected on the third or greater prostate biopsy, underscoring the importance of repeat prostate biopsy in the setting of increased or increasing prostate specific antigen despite negative previous prostate biopsy. Key Words: prostate, prostatic neoplasms, biopsy, prostate-specific antigen
rostate biopsy is indicated in the evaluation of men with increased PSA and/or abnormal DRE. Repeat PB is usually performed in men not found to have PC on the initial PB but with persistently increased or increasing PSA, PSA velocity greater than 0.75 ng/ml yearly, low free PSA, abnormal DRE or initial pathological finding related to an increased risk of cancer, such as high grade premalignant intraepithelial neoplasia or atypia.1–5 Previous studies have shown that on repeat PB patients are more likely to have indolent cancer3,6 – 8 and a more favorable prognosis. Moreover, some questions have arisen about whether repeat biopsy is justified after multiple negative biopsies in older men,9 especially since PB is not without risk and the likelihood of detecting clinically insignificant cancer is high.6,7 However, to our knowledge the pathological differences on initial vs repeat PB have not been previously reported in the literature. We investigated whether patients who undergo repeat PB in the face of prior
P
Submitted for publication January 28, 2008. Study received institutional review board approval. * Correspondence: Thomas Haider Biomedical Sciences Program, University of California-Riverside/University of California-Los Angeles, Riverside, California (e-mail: [email protected]). † Financial interest and/or other relationship with Pfizer, Cook, Abbott and Endocare.
0022-5347/08/1804-1325/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
negative biopsies have more favorable pathological outcomes in the biopsy specimens. MATERIALS AND METHODS Patient Characteristics We retrospectively reviewed the records of 2,309 patients in an institutional review board approved PB database who underwent PB positive for PC from 2000 to 2007 at Cleveland Clinic. Of the 2,309 patients 131 (5.7%) were excluded from study because of incomplete pathological data or a history of PC managed by prior radiotherapy, cryotherapy or hormonal therapy or active surveillance. Of the remaining 2,178 patients 905 (41.6%) had a new diagnosis of PC and were evaluated for clinical and biopsy pathological information, including primary and secondary GG, number of cores taken, number of cores positive for PC, percent maximum cancer in any given core and bilaterality. TRUS guided biopsy was performed with an 18 gauge needle biopsy gun after periprostatic nerve block beginning in 2001 and without periprostatic block before that time. Clinical and Pathological Analysis The clinical variables collected were patient age, race, serum PSA, biopsy GS, prostate volume, DRE, NuPB performed and biopsy schema with standard defined as fewer than 20
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Vol. 180, 1325-1329, October 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.06.022
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PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER TABLE 1. Clinical characteristics of 905 patients with newly diagnosed PC stratified by NegPBs No. NegPBs Factor
Mean ⫾ SD age No. black/total No. (%) No. median ng/ml PSA (IQR) No. abnormal DRE/total No. (%) No. biopsy schema/total No. (%): Standard (less than 20) Saturation (20 or greater) No. clinical stage T1c/total No. (%) Median cm3 prostate vol (IQR)
Initial Biopsy 66.7 ⫾ 9.3 82/690 (11.9) 6.2 (4.6–9.7) 78/675 (11.6) 558/683 125/683 597/675 40
(81.7) (18.3) (88.4) (25–48)
1
2 or Greater
65.5 ⫾ 8.6 12/142 (8.5) 6.4 (4.6–8.7) 13/139 (9.4) 58/142 84/142 126/139 42
66.7 ⫾ 7.5 6/73 (8.2) 10.7 (8.2–19.9) 5/71 (7.0)
(40.8) (59.2) (90.6) (26–55)
20/72 52/72 66/71 50
(27.8) (72.2) (93.0) (30–70)
p Value 0.36 0.36 0.41 0.42 ⬍0.01 0.42 ⬍0.01
Eight and 20 patients had missing information on biopsy schema and clinical stage T1c, respectively.
cores and saturation defined as 20 cores or greater. Prostate volume was measured by TRUS and by surgical prostatectomy specimen weight when unavailable, which was necessary in 20% of the patients. Biopsy specimens were reviewed by a genitourinary pathologist according to a previously described protocol, including primary and secondary Gleason scores.10 Clinically insignificant cancer was defined as PC fulfilling the Epstein criteria, including in 47 patients who satisfied all 4 available criteria (PSA density 0.4 ng/ml or less, 3 or fewer positive cores, 50% or less of maximum cancer in any core and GS 6 or less).11 Statistical Analysis The pathological outcome variables examined were GS, number of positive cores, maximum percent of cancer in any given core, bilaterality and clinically insignificant cancer. Patient demographics and clinical measures were used as covariates in the analysis. On univariate analysis Pearson’s chi-square test was used for comparisons of categorical variables and the t test or 1-way ANOVA was used for continuous variables. Percents or proportions are reported for categorical variables, and the medians and IQR are shown for continuous variables. Multivariate regression or logistic regression analysis was used to assess the relationship between outcome pathological features, including GS, number of positive cores, percent of positive core, maximum percent of cancer, bilaterality, clinically insignificant cancer and number of previous biopsies adjusted by patient demographic and clinical variables, such as age, DRE, PSA,
biopsy and prostate volume. All results were considered significant at ␣ ⫽ 0.05. Analyses were performed using the R statistical software package (Department of Statistics and Mathematics, Wirtschaftsuniversität Wien, Vienna, Austria). RESULTS A new PC diagnosis was made in 905 of the 2,178 biopsies performed (41.6%). PC was detected in 690 of 1,212 patients (56.9%) at initial biopsy, in 142 of 621 (22.9%) with 1 NegPB and in 73 of 345 (21.2%) with 2 or greater NegPBs. Table 1 lists the clinical characteristics of 905 patients with clinically localized PC stratified according to the number of PBs. There was no difference in patient age, race, serum PSA, DRE and clinical stage between initial and repeat biopsies. There was a statistically significant difference in biopsy schema (standard vs saturation), and between the initial and 1 NegPB compared to 2 or greater NegPBs (p ⬍0.01). A standard biopsy schema of fewer than 20 cores was used in 558 of 690 (80.9%), 58 of 142 (40.8%) and 20 of 73 cases (27.4%) in the initial PB, 1 NegPB and 2 or greater NegPBs groups (p ⬍0.01). Prostate volume increased with NuPB with a mean prostate volume of 40, 42 and 54 cm3 in the initial PB, 1 NegPB and 2 or greater NegPB groups (p ⬍0.01). Table 2 shows univariate analysis of clinical outcomes in patients according to NuPB. In the 3 groups the incidence of GS 5-6 in the first, second and third or greater PB was 358 of 690 (51.9%), 97 of 142 (68.3%) and 45 of 73 (61.6%),
TABLE 2. Needle biopsy pathological outcomes in 905 patients with newly diagnosed PC stratified by number of NegPBs NegPBs Factor No. pts No. GS (%): 5–6 3⫹4 4⫹3 8–10 Median cores (IQR): No. taken No. pos % Pos Max % involved (IQR) No. bilat/total No. (%) No. clinically insignificant Ca/total No. (%)
Initial Biopsy 689 358 150 96 85
1
2 or Greater
139 (52.0) (21.8) (13.9) (12.3)
12 (10–13) 3 (2–6) 25 (13–50) 30 (10–70) 291/680 (42.8) 37/480 (7.7)
97 19 12 11
73 (69.8) (13.7) (8.6) (7.9)
20 (11–20) 2 (1–5) 15 (10–25) 15 (5–50) 40/141 (28.4) 6/86 (7.0)
45 13 5 10
⬍0.01 (61.6) (17.8) (6.8) (13.7)
20 (12–20) 2 (1–3.5) 10 (5–25) 14 (5–40) 18/73 (24.7) 4/49 (8.2)
Four, 11 and 209 patients had missing information on GS, bilateral PC and clinically insignificant cancer, respectively.
p Value
⬍0.01
⬍0.01 ⬍0.01 0.96
PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER respectively (p ⬍0.01). PC was more likely to be GS 7 or greater on initial biopsy compared to repeat biopsy (331 of 690 cases or 48.0% vs 70 of 215 or 32.6%, p ⬍0.01). However, the incidence of GS 8 –10 cancer was 10 of 73 cases (13.7%) in the group with 2 or greater NegPBs compared with 85 of 690 (12.3%) and 11 of 142 (7.7%) in the initial PB and 1 NegPB groups, respectively (p ⫽ 0.26). As expected due to the preferential use of the saturation technique for repeat biopsies, the median number of cores was higher on repeat biopsy compared with that on initial biopsy (20 vs 12, p ⬍0.01). Despite this fact the mean number of cores with PC was 4.3, 3.4 and 3.0 in the initial PB, 1 NegPB and 2 or greater NegPBs groups, respectively (p ⬍0.01). There was an even more notable difference in the percent of cores positive for cancer (34.4%, 21.5% and 18.3%, respectively, p ⬍0.01). Additionally, the maximum percent of cancer in any given core was highest on initial biopsy compared to that on 1 NegPB and 2 or greater NegPBs (41% vs 29% and 27%, respectively, p ⬍0.01). PC was bilateral in 43% of cases on initial biopsy, in 28% on 1 NegPB and in 25% on 2 or greater NegPBs (p ⬍0.01). Finally, there was no difference in the rate of clinically insignificant cancer, as defined by the Epstein criteria,13 among the 3 groups, that is 7.7%, 7.0% and 8.2% in the initial PB, 1 NegPB and 2 or greater NegPB groups, respectively (p ⫽ 0.96). On multivariate linear regression analysis NuPB was an independent predictor of several pathological outcomes, including number of positive cores, percent of cores with PC, maximum involvement of a core with PC and bilaterality (p ⬍0.01, table 3). Of note, although age, PSA and DRE were significant predictors of GS, NuPB was not an independent predictor of this pathological outcome. Biopsy schema (standard vs saturation) predicted the number of positive cores (p ⬍0.01). However, biopsy schema predicted a lower percent of positive cores (p ⬍0.01).
DISCUSSION In our study PC was diagnosed in 57% of patients undergoing initial biopsy, 23% of those undergoing second biopsy and 21% undergoing third or greater biopsies. In comparison, in the prospective European Prostate Cancer Detection study Djavan et al performed PB in patients with PSA between 4 and 10 ng/ml, and found a PC detection rate of 24% and 13% for the first and second biopsies, respectively.7 We believe that the PC detection rates in the series of Djavan et al are lower compared to our findings likely due to the explanations provided and they are primarily related to their use of the sextant schema, which predominated in clinical practice at the time of their report. We found that the incidences of intermediate and high grade PC (GS 7 or greater) was 48%, 30% and 38% on initial PB, 1 NegPB and 2 or greater NegPBs, respectively. Other studies have shown the potential to detect high grade PC on repeat biopsies after negative prior biopsies. Djavan et al evaluated PC detection on biopsies 1 to 3 in patients with PSA 4 to 10 ng/ml and noted a mean of 31.1%, 29.8% and 8.2% GG 4/5 disease, respectively. Our study showed a higher percent of GG 4/5, including 48% on initial PB, 30.2% on 1 NegPB and 38.3% on 2 or greater NegPBs. In our study the percent of GS 8-10 was highest in the 2 NegPBs group vs
1327
TABLE 3. Predictors of clinical outcomes on multivariate analysis Clinical Variable Gleason score: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age No. pos cores: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age % Pos core: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age Max % Ca: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age Bilat: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age Epstein clinically insignificant Ca: NuPB Biopsy schema (less than 20 vs 20 or greater) PSA (continuous) DRE Age
Coefficient
p Value
⫺0.0741 ⫺0.1293
0.253 0.125
0.0003 0.5079 0.0325
0.010 ⬍0.01 ⬍0.01
⫺0.8536 0.8321
⬍0.01 0.022
⫺0.0001 0.9886 0.0320
0.825 0.048 0.066
⫺4.9308 ⫺12.0219
⬍0.01 ⬍0.01
⫺0.0020 12.7257 0.2121
0.622 ⬍0.01 0.033
⫺8.2716 0.2084
⬍0.01 0.938
0.0025 13.6917 0.4125
0.525 ⬍0.01 ⬍0.01
⫺0.4612 ⫺0.0382
⬍0.01 0.829
0.0001 0.1803 0.0239
0.760 0.459 0.003
0.0470 0.0597
0.864 0.869
0.0004 1.0674 ⫺0.076
0.465 0.019 ⬍0.01
the initial PB and 1 NegPB groups (14% vs 12% and 8%, respectively). The lower PC detection rates and GG 4/5 incidence in the study of Djavan et al may be explained by the practice pattern and biopsy technique, which also differed from ours based on their practice of recommending repeat biopsies automatically 6 to 8 weeks after an initial negative biopsy. However, we performed repeat biopsy based on clinical suspicion according to the factors described. Moreover, Djavan et al performed standard sextant biopsy with 2 additional transition zone biopsies. Routine transition zone biopsies have not been shown to contribute significantly more information and they are not currently recommended.12 Notably Haas et al found that sextant biopsy missed most tumors in a recent autopsy series,12 providing further evidence that sextant biopsy has a high false-negative detection rate. Although the PC detection rate decreased with increasing negative PB, our study shows that a significant percent of high grade cancer still remains at the third or greater biopsy. Consistent with our data, Epstein et al studied radical prostatectomy specimens and found 12% positive surgical margin and 27% nonorgan confined PC rates in patients diagnosed with PC after benign initial biopsies.6 These findings indicate that prior benign biopsies in men subsequently diagnosed with PC do not define indolent tumor. Prior studies demonstrate improved cancer detection with saturation biopsy on repeat biopsy.13,14 Cancer detec-
1328
PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER
tion rates between 13.5% and 44% have been reported with saturation biopsy in patients undergoing rebiopsy.13 On our multivariate analysis biopsy schema predicted the number of positive cores and the percent of positive cores on PB. As the number of cores taken increased, patients were likely to have a higher number of positive cores with a lower overall percent of positive cores. We believe that these data show that the extent of cancer is better defined in this setting by taking more cores. Although our univariate analysis suggested that PC on initial biopsy was more likely to be GS 7 or greater compared to PC diagnosed on a second biopsy, on our multivariate analysis NuPB was not an independent predictor of GS. Only PSA, DRE and age were independent predictors of GS on biopsy. In 2004 Stamey et al reported that PSA no longer correlates with the percent of GG 4/5 and it correlates only weakly with cancer volume, leading them to conclude that PSA is useful only as a marker of benign prostatic hyperplasia.15 Recent studies suggest that preoperative PSA is still predictive of cancer volume,16,17 grade16 and indolent cancer.18 Also, it is important to understand that Stamey et al drew their conclusions that PSA correlated poorly with GS and tumor volume from a highly select population of patients who underwent radical prostatectomy,15 overlooking the fact that only a small percent of men, even if diagnosed with PC, undergo this operation. In the current study PSA predicted GS on subsequent biopsies and age was an independent predictor of GS and tumor volume on multivariate analysis. Thus, as Hong et al pointed out, the relationship of PSA to cancer status in patients with known cancer may be limited but in an overall screening or biopsy population there remains a close link of PSA and cancer risk.19 Although prior studies have shown that cancer identified on repeat biopsy is typically lower volume and carries less risk than cancer found during the initial prostate biopsy,3,6,7 to our knowledge our study is the first to consider biopsy pathological outcomes in the extended biopsy era and our multivariate analysis revealed that NuPB is an important predictor of biopsy pathological outcomes. Patients with prior negative biopsies are more likely to have lower volume cancer and less likely have bilateral cancer. Nevertheless, our findings suggest that these patients are still at significant, if not increased, risk for high grade, localized cancer in the highly selective setting of repeat biopsy for persistently suspicious findings following prior NegPBs. The clinical implication of diligent followup in this setting is that these tumors may be significant and have a higher likelihood of cure based on size. Thus, detection may be particularly important in the setting of persistently increased or increasing PSA following negative biopsy, especially if only a single prior sextant biopsy was performed. To our knowledge our study is the first to evaluate all patients with PC diagnosed on biopsy irrespective of final management. Thus, our findings reflect the real-life situation that urologists face prospectively when reviewing various management options with patients. The most significant limitations of this study are its retrospective nature, and lack of pathological and prognostic outcomes. In addition, biopsies were performed by different urologists and, thus, there is likely to have been some variations in the indications for biopsy and in the exact techniques used for biopsy and prostate volume measurement. Moreover, there is a
limited correlation between TRUS volume and surgical specimen weight for 20% of the prostate volumes measured (r ⫽ 0.70).20 Furthermore, the proportion of biopsies using the saturation technique was likely based on the referral nature of our practice. Many such patients are referred for saturation biopsy in the office after 1 or more negative biopsies when there is persistent suspicion of cancer. Thus, the rate of saturation biopsy is higher than in most current reports, so that our detection rate may be higher than would have been predicted using less aggressive biopsy schemes. CONCLUSIONS Given that PB is not without risk or inconvenience, the indications for repeat biopsy after 1 or more negative PBs have not been clearly defined and actual clinical practice has varied greatly. We found that 38% of cancers diagnosed after 2 or more NegPBs were intermediate or high grade (GS 7 or greater), including 14% that were GS 8-10. Thus, although multiple negative prior biopsies may portend improved pathological outcomes, a significant number of patients have aggressive high risk cancers despite negative previous evaluation. Although cancers found at repeat biopsy are smaller and other pathological features are in general more encouraging, it appears justified to consider repeat biopsy if concerning clinical or prior biopsy findings exist.
Abbreviations and Acronyms DRE GG GS NegPB NuPB PB PC PSA TRUS
⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽
digital rectal examination Gleason grade Gleason sum negative previous biopsy number of previous biopsies prostate biopsy prostate cancer prostate specific antigen transrectal ultrasound
REFERENCES 1.
Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R et al: Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 1992; 267: 2215. 2. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A et al: Use of the percentage of free prostatespecific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 1998; 279: 1542. 3. Lopez-Corona E, Ohori M, Wheeler TM, Reuter VE, Scardino PT, Kattan MW et al: Prostate cancer diagnosed after repeat biopsies have a favorable pathological outcome but similar recurrence rate. J Urol 2006; 175: 923. 4. Park S, Shinohara K, Grossfeld GD and Carroll PR: Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy. J Urol 2001; 165: 1409. 5. Potter SR, Horniger W, Tinzl M, Bartsch G and Partin AW: Age, prostate-specific antigen, and digital rectal examination as determinants of the probability of having prostate cancer. Urology 2001; 57: 1100. 6. Epstein JI, Walsh PC, Akingba G and Carter HB: The significance of prior benign needle biopsies in men subsequently diagnosed with prostate cancer. J Urol 1999; 162: 1649.
PROSTATE CANCERS DIAGNOSED AT REPEAT BIOPSY ARE SMALLER 7.
8.
9.
10.
11.
12.
13. 14.
15.
16.
17.
18.
19.
Djavan B, Ravery V, Zlotta A, Dobronski P, Dobrovits M, Fakhari M et al: Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J Urol 2001; 166: 1679. Epstein JI, Walsh PC, Sauvageot J and Carter HB: Use of repeat sextant and transition zone biopsies for assessing extent of prostate cancer. J Urol 1997; 158: 1886. Hoffman RM, Denberg T, Hunt WC and Hamilton AS: Prostate cancer testing following a negative prostate biopsy: over testing the elderly. J Gen Intern Med 2007; 22: 1139. Epstein JI, Allsbrook WC Jr, Amin MB and Egevad LL: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005; 29: 1228. Epstein JI, Walsh PC, Carmichael M and Brendler CB: Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994; 271: 368. Haas GP, Delongchamps NB, Jones RF, Chandan V, Serio AM, Vickers AJ et al: Needle biopsies on autopsy prostates: sensitivity of cancer detection based on true prevalence. J Natl Cancer Inst 2007; 99: 1484. Jones JS: Saturation biopsy for detecting and characterizing prostate cancer. BJU Int 2007; 99: 1340. Jones JS, Patel A, Schoenfield L, Rabets JC, Zippe CD and Magi-Galluzzi C: Saturation technique does not improve cancer detection as an initial prostate biopsy strategy. J Urol 2006; 175: 485. Stamey TA, Caldwell M, McNeal JE, Nolley R, Hemenez M and Downs J: The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004; 172: 1297. Figler BD, Reuther AM, Dhar N, Levin H, Magi-Galluzzi C, Zhou M et al: Preoperative PSA is still predictive of cancer volume and grade in late PSA era. Urology 2007; 70: 711. Ochiai A, Troncoso P and Babaian RJ: The relationship between serum prostate specific antigen level and tumor volume persists in the current era. J Urol 2007; 177: 903. Steyerberg EW, Roobol MJ, Kattan MW, van der Kwast TH, de Koning HJ and Schroder FH: Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol 2007; 177: 107. Hong YM, Lai FC, Chon CH, McNeal JE and Presti JC Jr: Impact of prior biopsy scheme on pathologic features of
20.
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cancers detected on repeat biopsies. Urol Oncol 2004; 22: 7. Sajadi KP, Terris MK, Hamilton RJ, Cullen J, Amling CL, Kane CJ et al: Body mass index, prostate weight and transrectal ultrasound prostate volume accuracy. J Urol 2007; 178: 990.
EDITORIAL COMMENT The decision to repeat PB has many implications, including a risk-benefit assessment. These authors report that in their experience cancer on repeat biopsies is found frequently (21% of cases), is aggressive (GS 7 and 8-10 in 32% and 14%) and is not indolent (7% and 8% on initial and repeat biopsy, respectively). However, patients who undergo rebiopsy had more cores taken, larger prostate glands, and fewer and a lower percent of cores with cancer. Age, PSA and DRE were again found to correlate with pathological features, including GG but the number of previous biopsies was not. They concluded that in cases at continuous suspicion for cancer repeat biopsy detects significant cancer and when using saturation biopsy, over diagnosis is not a concern. It should be emphasized that these results can be related to the high risk nature of their patients (high rate of GS greater than 7), the rebiopsy scheme protocol (high rate of cancer), and the criteria for and timing of rebiopsy (low incidence of indolent cancer). Although factors such as atypia, HGPIN (reference 1 in article), free PSA and PSA kinetics1 were not evaluated, it is clear that if there is a clinical reason to suspect cancer, rebiopsy is certainly appropriate. Ernesto López-Corona Department of Urology Hospital Angeles Tijuana Onco-Urology Service Hospital General de Tijuana Tijuana, Baja California Mexico 1.
Park SJ, Miyake H, Hara I and Eto H: Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy. Int J Urol 2003; 10: 68.