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Journal of Clinical Oncology, Vol 18, Issue 15 (August), 2000: 2862-2868
© 2000 American Society for Clinical Oncology

Preoperative Prediction of Surgical Margin Status in Patients With Prostate Cancer Treated by Radical Prostatectomy

By Liang Cheng, Jeff Slezak, Erik J. Bergstralh, Robert P. Myers, Horst Zincke, David G. Bostwick

From the Department of Pathology and Urology, Indiana University School of Medicine, Indianapolis, IN, and the Section of Biostatistics and the Department of Urology, Mayo Clinic, Rochester, MN; and Bostwick Laboratories, Richmond, VA.

Address reprint requests to Liang Cheng, MD, Department of Pathology, University Hospital 3465, Indiana University School of Medicine, 550 North University Blvd, Indianapolis, IN 46202; email lcheng{at}iupui.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: We sought to determine the preoperative factors associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer.

PATIENTS AND METHODS: The study group consisted of 339 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic. None received preoperative adjuvant therapy. The mean age at the time of surgery was 66 years (range, 45 to 79 years). All specimens were totally embedded and whole-mounted. Positive surgical margin was defined as the presence of cancer cells at the inked margins. Numerous pathologic characteristics in needle biopsies and preoperative clinical findings were analyzed.

RESULTS: The overall margin positivity rate was 24%. In univariate analysis, preoperative serum prostate-specific antigen (PSA) level, Gleason score, perineural invasion, percentage of cancer in the biopsy specimens, and number and percentage of biopsy cores involved by cancer were all associated with positive surgical margins. In multivariate analysis, preoperative serum PSA level (odds ratio for a doubling of PSA levels, 1.9; 95% confidence interval, 1.5 to 2.4; P < .001) and percentage of cancer in the biopsy specimens (odds ratio for a 10% increase, 1.3; 95% confidence interval, 1.2 to 1.4; P < .001) were predictive of margin status in radical prostatectomy. With use of preoperative serum PSA level and percentage of cancer in the biopsy as predictors of surgical margins, the overall accuracy as measured by the area under the receiver operating characteristic curve was 0.74.

CONCLUSION: Preoperative serum PSA level and percentage of cancer in the biopsy specimens were independently associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. The combination of these two factors provides a high level of predictive accuracy for margin status.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
THE WIDESPREAD USE of serum prostate-specific antigen (PSA) testing has led to the identification of an increasing number of patients with early-stage prostate cancer.1 Radical prostatectomy is considered an appropriate treatment for selected candidates.2,3 Unfortunately, approximately one third of patients who undergo prostatectomy will have positive surgical margins,4-7 and these patients have increased risk of local and systemic cancer progression.4-16 The use of preoperative adjuvant therapy will reduce the incidence of positive margins, although its long-term impact on survival is less certain.17-23 The preoperative identification of patients at risk of positive margins may be helpful for selection of candidates for nerve-sparing surgery14,24 and modified surgical procedures.25 Thus, there is a substantial need for preoperative predictors of surgical margins. Several investigations have correlated preoperative findings with margin status,15,26-34 but these studies are limited by small sample size, incomplete biopsy data or clinical information, variation in prostatectomy specimen processing and lack of standardized criteria for positive margins, inclusion of patients with preoperative adjuvant therapy, and lack of multivariate analysis. In this study, we evaluate a number of preoperative clinical and biopsy findings to determine independent predictors of surgical margin status in patients with prostate cancer treated by radical prostatectomy and bilateral pelvic lymphadenectomy.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
The study population consisted of 339 patients treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between August 1987 and September 1993 at the Mayo Clinic. Patients who received preoperative adjuvant therapy were excluded. All patients underwent complete medical examination and preoperative staging, including chest and pelvic conventional radiographs.3,35-37 Bone scan was performed as clinically indicated. None had clinical evidence of distant metastasis at radical prostatectomy. Within 120 days of prostatectomy, serum PSA level was measured using the Hybritech Tandem-R PSA assay (Hybritech, San Diego, CA) in all patients. Clinical stage was obtained before surgery and assigned according to the tumor-node-metastasis classification system.38

Needle Biopsy Specimens
Biopsy was performed in all patients within 3 months before radical prostatectomy. The specific indication for biopsy and the biopsy technique varied between individual urologists and were not standardized. In each biopsy specimen, we evaluated Gleason primary and secondary patterns (grades), Gleason score (sum of the primary and secondary grades), nuclear grade, the presence or absence of perineural invasion, the presence or absence of high-grade prostatic intraepithelial neoplasia (PIN), percentage of cancer in the biopsy specimens (in 10% increments), the number of needle core fragments that contained cancer, and the greatest percentage of cancer in any positive needle cores.39-43

Radical Prostatectomy Specimens
The radical prostatectomy and bilateral pelvic lymphadenectomy specimens were examined as previously described.39-45 Each prostate was weighted, measured, inked, and fixed for up to 3 days in 10% neutral formalin. After fixation, the apex and base were amputated and serially sectioned at approximately 3- to 5-mm intervals in the vertical parasagittal plane. The seminal vesicles were sectioned parallel to the junction of the prostate and submitted entirely for examination. The remaining prostate was serially sectioned by knife perpendicular to the long axis of the gland from the apex of the prostate to the tip of the seminal vesicle, and whole-mount prostates or subdivided transverse sections were prepared. Surgical margins were considered positive when cancer cells were in contact with the inked margin. Pathologic staging was performed according to the 1997 tumor-node-metastasis (tumor, lymph nodes, and metastasis) system.38 Pathologic stage was T2a (n = 24 patients), T2b (n = 173), T3a (n = 71), T3b (n = 49), and T2-3N+ (n = 22). The Gleason system was used for the grading of the primary cancer.46 Gleason scores in the prostatectomy were 2 (n = 0 patients), 3 (n = 1), 4 (n = 42), 5 (n = 59), 6 (n = 87), 7 (n = 112), 8 (n = 34), 9 (n = 4), and 10 (n = 0).

Statistical Analysis
Univariate association between preoperative variables and surgical margin status was analyzed using logistic regression analysis. Stepwise logistic regression analysis was used to identify a set of independent preoperative predictors of positive margins; the variables entered in the models were age, preoperative PSA levels, clinical stage, Gleason grade, nuclear grade, perineural invasion, high-grade PIN, percentage of cancer in the biopsy specimens, number of biopsy cores involved by cancer, percentage of biopsy cores that were positive for cancer, and highest percentage of cancer in any positive needle cores. Preoperative serum PSA level was analyzed on the log-2 scale.

Receiver operating characteristic (ROC) analysis47 was used to evaluate the usefulness of logistic score based on serum PSA level and percentage of cancer in the biopsy specimens as independent predictors for surgical margins in prostatectomy specimens. For each patient, a predicted risk of positive margins was computed from the multivariate model. Sensitivity and specificity were calculated for each level of this predicted risk observed in the sample by varying the predicted risk that signified a positive test (threshold level). Sensitivity was defined as having positive margins that had a predicted risk greater than the threshold level, whereas specificity was defined as having negative margins that had a predicted risk less than the threshold level. The ROC curve is a plot of sensitivity versus specificity for all possible cut points.47 The accuracy of models for predicting positive margins was assessed based on the area under the ROC curve, which equals 1 for a perfect test and 0.5 for a test that is no better than chance at predicting positive margins. All tests were two-sided, with P < .05 being considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The preoperative findings, including clinical variables and needle biopsy findings, are listed in Table 1. The mean patient age at prostatectomy was 66 years (range, 45 to 79 years; median, 67 years). Preoperative serum PSA levels ranged from 0.6 to 122 ng/mL (mean, 14.3 ng/mL; median, 9.4 ng/mL). The clinical stages were T1c (n = 82 patients), T2a (n = 186), T2b (n = 48), T3a (n = 17), and T3b (n = 5) and was unknown in one patient.


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  		Table 1. Univariate Analysis of Factors Predictive of Margin Status in 339 Patients Treated by Radical Prostatectomy
 
All pathologic variables were obtained from the biopsy specimen. Biopsy Gleason scores ranged from 3 to 9 (mean, 5.5; median, 5.0). Perineural invasion was present in 130 patients (38%) and high-grade PIN in 177 (52%). The percentage of cancer in the biopsy ranged from 5% to 100% (mean, 33%; median, 30%). The mean number of biopsy cores obtained was 5.6 (median, 6.0; range, one to 18). The number of needle cores involved by cancer ranged from one to 10 (mean, 2.8; median, 3.0).

All patients underwent radical prostatectomy and bilateral pelvic lymphadenectomy. Positive surgical margins were present in 83 patients (24%). In univariate analysis, preoperative serum PSA level, Gleason primary pattern, Gleason secondary pattern, Gleason score (sum of the primary and secondary patterns), perineural invasion, percentage of cancer in the biopsy specimens, and the number of biopsy cores involved by cancer were all predictive of surgical margin status in radical prostatectomy (Table 1). Age, clinical stage, and the greatest percentage of cancer involvement in positive needle cores were not associated with margin status (Table 1)

In multivariate analysis, preoperative serum PSA level (P < .001) and percentage of cancer in the biopsy specimens (P < .001) were significant independent predictors of margin status in radical prostatectomy (Table 2). The estimated odds ratio (approximate relative risk) for positive margins for a man with a PSA level twice that of another man (doubling in PSA level) was 1.9 with a 95% confidence interval of 1.5 to 2.4. Similarly, the odds ratio for a man whose percentage of cancer in the biopsy was 10 units higher than another man was 1.3 (95% confidence interval, 1.2 to 1.4).


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  		Table 2. Multivariate Analysis of Preoperative Factors Predictive of Margin Status in Patients Who Underwent Prostatectomy for Prostate Cancer
 
ROC analysis of preoperative serum PSA level and percentage of cancer in the biopsy specimens as predictors of surgical margins was performed. The overall accuracy as measured by the area under the curve was 0.74 (Fig 1). Patients with serum PSA levels less than 4 ng/mL and the percentage of cancer in the biopsy less than 10% had 14% of risk for positive margins, compared with 79% risk of positive margins among patients with serum PSA levels greater than 20 ng/mL and percentage of cancer in the biopsy greater than 40% (Table 3). A model that contained preoperative serum PSA level and percentage of biopsy cores positive (computed as the number of cores that contained cancer divided by the number of cores sampled) had similar predictive ability (area under the ROC curve, 0.76) and was useful when the exact percentage of cancer in the biopsy was not available.



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  		Fig 1. ROC analysis showing the sensitivity and specificity of the logistic regression model, including preoperative PSA level and percentage of cancer in biopsy specimens, in predicting surgical margin status. Sensitivity is the probability of predicting positive margins when they exist, and specificity is the probability of negative prediction when the margins truly are negative. The area under the curve is 0.74.

 

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  		Table 3. Observed and Predicted Rates of Margin Positivity Based on the Preoperative Serum PSA Level and the Percentage of Cancer in the Biopsy Specimens
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Accurate preoperative prediction of surgical margin status would be clinically useful to plan treatment, especially for patients being considered for nerve-sparing procedures and/or preoperative adjuvant therapy. In this study, we evaluated a constellation of readily available preoperative variables to determine the best predictor(s) of surgical margin status in a cohort of 339 untreated patients who underwent radical prostatectomy for prostate cancer. We found that preoperative serum PSA level and percentage of cancer in the biopsy specimens are independently associated with surgical margin status. The combination of these two factors provides information about risk of positive margins in patients who have undergone prostatectomy for prostate cancer.

The presence of positive surgical margins is considered a poor prognostic factor for patients who were treated by radical prostatectomy for prostate cancer.4,5,7 Epstein et al9 studied 617 patients with prostate cancer without lymph node metastasis or seminal vesical invasion and found that involvement of surgical margins by cancer had independent prognostic significance relative to the impact of extracapsular extension. We found that margin status and DNA ploidy were independent predictors of cancer progression regardless of the presence or absence of extracapsular extension in patients with prostate cancer treated by radical prostatectomy and bilateral pelvic lymphadenectomy.7 In a multivariate analysis of 347 patients, D’Amico et al48 found that extraprostatic extension was not a significant independent predictor of PSA failure, whereas positive surgical margins and Gleason grade were significant independent predictors. Paulson et al12,13 reported that patients with positive margins were associated with decreased cancer-specific and overall survival. The accumulative data suggest that surgical margin status is an important predictor of patient outcome and that the ability for preoperative prediction of surgical margin status may have important clinical implications.

In a previous study, we demonstrated that the best preoperative prediction of extraprostatic extension and seminal vesical invasion was obtained by serum PSA, Gleason score, and percentage of cancer in the biopsy specimens.39 Models based on the combination of these factors will allow for more accurate stratification of patients for therapeutic interventions.39,49 Few studies have directly assessed preoperative variables for prediction of surgical margins, and only limited biopsy information was available for analysis in these studies.15,26-34 Tigrani et al26 studied 108 patients who underwent prostatectomy for prostate cancer and found that the number of positive biopsies was the best predictor of margin status. Preoperative serum PSA level, biopsy Gleason score, and primary grade were not significant in predicting margin status.26 In contrast, Watson et al15 found that patients with positive margins tend to have greater biopsy Gleason scores than do those with negative margins (P = .05). Preoperative serum PSA level and clinical stage were not associated with margin status.15 Ravery et al29 found that the percentage of cancer in biopsy specimens differed significantly between patients with positive margins and those with negative margins, but none of other preoperative variables was analyzed. Ackerman et al28 showed that the number of positive biopsies, preoperative serum PSA level, and PSA density were all significant predictors of margin status in univariate analysis; biopsy Gleason scores, however, were not associated with margin status. Multivariate analysis identified the number of positive biopsies as the most significant predictor of margin status.28 Rabbani et al27 found that PSA density was the only significant predictor of margin status among patients without preoperative adjuvant therapy. Shelfo et al32 showed that patients with PSA levels >= 10 ng/mL had a greater incidence of positive margins. However, Gomez et al31 did not find a correlation between preoperative serum PSA level and margin status in a cohort of 50 patients.

We found that preoperative serum PSA level, biopsy Gleason score, primary grade, secondary grade, perineural invasion, percentage of cancer in the biopsy specimens, and number of positive biopsies involved by cancer were all predictive of margin status in the univariate analysis. Clinical stage was marginally associated with surgical margin status (P = .057). Age, biopsy nuclear grade, high-grade PIN, and the greatest percentage of cancer involvement in positive cores were not significant predictors of margin status. Multivariate analysis identified preoperative serum PSA level and percentage of cancer in the biopsy as independent predictors of margin status. With the use of these two variables as predictors of surgical margin status, the overall accuracy as measured by the area under the ROC curve was 0.74. For example, a patient with a preoperative serum PSA level of less than 4 ng/mL and less than 10% cancer in the biopsy has an estimated (based on logistic model) 11% chance of positive margins, whereas a patient with a preoperative serum PSA level of 10 to 20 ng/mL and greater than 40% cancer in the biopsy has an estimated 59% chance of positive margins (Table 3). An alternative model that uses preoperative PSA level and percentage of positive biopsy cores demonstrated similar prognostic ability and may be useful in cases in which the exact percentage of cancer in the biopsies is unavailable. Our data suggest that the likelihood of a positive surgical margin is directly linked to tumor volume. The combination of preoperative serum PSA level and percentage of cancer in the biopsy (alternatively, percentage of positive biopsy cores) may provide information on tumor extent at the time of diagnosis.

We have previously demonstrated that the percentage of cancer in the biopsy specimens is the most accurate predictor of cancer volume in the radical prostatectomy specimens among three routinely used methods for measuring the cancer volume in the needle biopsy specimens, including percentage of cancer in the biopsy, percentage of biopsy cores involved, and millimeters of cancer per biopsy cores.41 Although ideal markers for final tumor volume are yet to be identified, the use of percentage of cancer in biopsy specimens as a surrogate for tumor volume has certain advantages, including being easy to use, convenient, practical, and readily available. The number or percentage of positive cores may be used when the percentage of cancer in the biopsy is not available if the following are recognized: (1) prostate cancer is multifocal and irregular in shape, and thus, the involvement of multiple biopsy cores may not necessarily indicate a large volume cancer; and (2) there is a significant variation in biopsy techniques, and the length of biopsy cores is not always the same. We recommend that the percentage of cancer in the biopsy specimens be reported in the examination of needle biopsies.40

Accurate preoperative prediction of margin status could be of value in the selection of therapeutic strategies for individual patients. The utility of current analysis seems to be limited. Although the extremes define low- and high-risk groups for positive margins, there remains a large group of men who are at significant but intermediate risk (20% to 35%). The predictive accuracy for surgical margins may be improved with the use of the multiple prognostic index and novel imaging techniques. Current radiographic imaging methods, such as transrectal ultrasound, pelvic computerized tomography, and pelvic magnetic resonance imaging (MRI), are of limited use, with low accuracy for determining the tumor extent. Endorectal MRI seems to be promising for preoperative identification of patients at risk of positive margins,50 although Cornud et al51 refuted the use of endorectal MRI for predicting margin status. Future studies should evaluate the independent predictive values of other preoperative factors, including DNA ploidy analysis by digital image analysis, microvessel density assay, reverse transcriptase polymerase chain reaction detection of circulating PSA-positive cells, fluorescence in situ hybridization for chromosomal anomalies, and endorectal MRI. The development of neural network and multiple prognostic index by combining these novel diagnostic modalities and routinely available preoperative variables may provide a high level of accuracy for predicting margin status.

In summary, preoperative serum PSA level and percentage of cancer in the biopsy specimens were independent predictors of surgical margin status in patients who underwent radical prostatectomy for prostate cancer. The combination of these two factors provides an estimation of the risk for positive margins; thus, this information may be useful for the stratification of patients for treatments, such as selection of candidates for preoperative adjuvant therapy and/or nerve-sparing prostatectomy and modified surgical techniques.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
1. Mettlin C: The American Cancer Society National Prostate Cancer Detection Project and national patterns of prostate cancer detection and treatment. CA Cancer J Clin 47:265-272, 1997[Abstract]

2. Gerber GS, Thisted RA, Scardino PT, et al: Results of radical prostatectomy in men with clinically localized prostate cancer. JAMA 276:615-619, 1996[Abstract]

3. Zincke H, Oesterling JE, Blute ML, et al: Long-term (15 years) results after radical prostatectomy for clinically localized (stage T2c or lower) prostate cancer. J Urol 152:1850-1857, 1994[Medline]

4. Wieder JA, Soloway MS: Incidence, etiology, location, prevention, and treatment of positive surgical margins after radical prostatectomy for prostate cancer. J Urol 160:299-315, 1998[Medline]

5. Blute ML, Bostwick DG, Seay TM, et al: Pathologic classification of prostate carcinoma: The impact of margin status. Cancer 82:902-908, 1998[Medline]

6. Blute ML, Bostwick DG, Bergstralh EJ, et al: Anatomic site-specific positive margins in organ-confined prostate cancer and its impact on outcome after radical prostatectomy. Urology 50:733-739, 1997[Medline]

7. Cheng L, Darson MF, Bergstralh EJ, et al: Correlation of margin status and extraprostatic extension with progression of prostate carcinoma. Cancer 86:1775-1782, 1999[Medline]

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9. Epstein JI, Partin AW, Sauvageot J, et al: Prediction of progression following radical prostatectomy: A multivariate analysis of 721 men with long-term follow-up. Am J Surg Pathol 20:286-292, 1996[Medline]

10. Catalona WJ, Smith DS: 5-year tumor recurrence rates after anatomic radical retropubic prostatectomy for prostate cancer. J Urol 152:1837-1842, 1994[Medline]

11. Paulson DF, Stone AR, Walther PJ, et al: Radical prostatectomy: Anatomical predictors of success or failure. J Urol 136:1041-1043, 1986[Medline]

12. Paulson DF, Moul JW, Walther PJ: Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: Long-term results. J Urol 144:1180-1184, 1990[Medline]

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14. Smith RC, Partin AW, Epstein JI, et al: Extended follow-up of the influence of wide excision of the neurovascular bundle(s) on prognosis in men with clinically localized prostate cancer and extensive capsular perforation. J Urol 156:454-458, 1996[Medline]

15. Watson RB, Civantos F, Soloway MS: Positive surgical margins with radical prostatectomy: Detailed pathological analysis and prognosis. Urology 48:80-90, 1996[Medline]

16. Weldon VE, Tavel FR, Neuwirth H, et al: Patterns of positive specimen margins and detectable prostate specific antigen after radical perineal prostatectomy. J Urol 153:1565-1569, 1995[Medline]

17. Soloway MS, Watson R: The role of induction androgen deprivation prior to radical prostatectomy. Eur Urol 29:114-118, 1996

18. Soloway MS, Sharifi R, Wajsman Z, et al: Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer: The Lupron Depot Neoadjuvant Prostate Cancer Study Group. J Urol 154:424-428, 1995[Medline]

19. Goldenberg SL, Klotz LH, Srigley J, et al: Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer. J Urol 156:873-877, 1996[Medline]

20. Van Poppel H, De Ridder D, Elgamal AA, et al: Neoadjuvant hormonal therapy before radical prostatectomy decreases the number of positive surgical margins in stage T2 prostate cancer: Interim results of a prospective randomized trial. J Urol 154:429-434, 1995[Medline]

21. Fradet Y: The role of neoadjuvant androgen deprivation prior to radical prostatectomy. Urol Clin North Am 23:575-585, 1996[Medline]

22. Lee F, Siders DB, McHug TA, et al: Long-term follow-up of stages T2–T3 prostate cancer pretreated with androgen ablation therapy prior to radical prostatectomy. Anticancer Res 17:1507-1510, 1997[Medline]

23. Rabbani F, Sullivan LD, Goldenberg SL, et al: Neoadjuvant androgen deprivation therapy before radical prostatectomy: Who is unlikely to benefit? Br J Urol 79:221-225, 1997[Medline]

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25. Stephenson RA, Middleton RG, Abbott TM: Wide excision (nonnerve sparing) radical retropubic prostatectomy using an initial perirectal dissection. J Urol 157:251-255, 1997[Medline]

26. Tigrani VS, Bhargava V, Shinohara K, et al: Number of positive systematic sextant biopsies predicts surgical margin status at radical prostatectomy. Urology 54:689-693, 1999[Medline]

27. Rabbani F, Goldenberg SL, Klotz LH: Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy: The Canadian Urologic Oncology Group. J Urol 159:925-928, 1998[Medline]

28. Ackerman DA, Barry JM, Wicklund RA, et al: Analysis of risk factors associated with prostate cancer extension to the surgical margin and pelvic node metastasis at radical prostatectomy. J Urol 150:1845-1850, 1993[Medline]

29. Ravery V, Schmid HP, Toublanc M, et al: Is the percentage of cancer in biopsy cores predictive of extracapsular disease in T1–T2 prostate carcinoma? Cancer 78:1079-1084, 1996[Medline]

30. Ravery V, Szabo J, Toublanc M, et al: A single positive prostate biopsy in six does not predict a low-volume prostate tumour. Br J Urol 77:724-728, 1996[Medline]

31. Gomez CA, Soloway MS, Civantos F, et al: Bladder neck preservation and its impact on positive surgical margins during radical prostatectomy. Urology 42:689-694, 1993[Medline]

32. Shelfo SW, Obek C, Soloway MS: Update on bladder neck preservation during radical retropubic prostatectomy: Impact on pathologic outcome, anastomotic strictures, and continence. Urology 51:73-78, 1998

33. Wahle S, Reznicek M, Fallon B, et al: Incidence of surgical margin involvement in various forms of radical prostatectomy. Urology 36:23-26, 1990[Medline]

34. Sanwick JM, Dalkin BL, Nagle RB: Accuracy of prostate needle biopsy in predicting extracapsular tumor extension at radical retropubic prostatectomy: Application in selecting patients for nerve-sparing surgery. Urology 52:814-819, 1998[Medline]

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36. Zincke H, Bergstralh EJ, Blute ML, et al: Radical prostatectomy for clinically localized prostate cancer: Long-term results of 1,143 patients from a single institution. J Clin Oncol 12:2254-2263, 1994[Abstract/Free Full Text]

37. Lerner SE, Blute ML, Bergstralh EJ, et al: Analysis of risk factors for progression in patients with pathologically confined prostate cancers after radical retropubic prostatectomy. J Urol 156:137-143, 1996[Medline]

38. Fleming ID, Cooper JS, Henson DE, et al: AJCC Cancer Staging Manual. Philadelphia, PA,Raven and Lippincott, 1997

39. Bostwick DG, Qian J, Bergstralh E, et al: Prediction of capsular perforation and seminal vesicle invasion in prostate cancer. J Urol 155:1361-1367, 1996[Medline]

40. Bostwick DG: Evaluating prostate needle biopsy: Therapeutic and prognostic importance. CA Cancer J Clin 47:297-319, 1997[Abstract]

41. Cupp MR, Bostwick DG, Myers RP, et al: The volume of prostate cancer in the biopsy specimen cannot reliably predict the quantity of cancer in the radical prostatectomy specimen on an individual basis. J Urol 153:1543-1548, 1995[Medline]

42. Egan AJ, Bostwick DG: Prediction of extraprostatic extension of prostate cancer based on needle biopsy findings: Perineural invasion lacks significance on multivariate analysis. Am J Surg Pathol 21:1496-1500, 1997[Medline]

43. Dugan JA, Bostwick DG, Myers RP, et al: The definition and preoperative prediction of clinically insignificant prostate cancer. JAMA 275:288-294, 1996[Abstract]

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48. D’Amico AV, Whittington R, Malkowicz SB, et al: A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer. J Urol 154:131-138, 1995[Medline]

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51. Cornud F, Belin X, Flam T, et al: Local staging of prostate cancer by endorectal MRI using fast spin-echo sequences: Prospective correlation with pathological findings after radical prostatectomy. Br J Urol 77:843-850, 1996[Medline]

Submitted November 22, 1999; accepted March 21, 2000.




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