Repeat transrectal ultrasound-guided prostate biopsy: a strategy to improve the reliability of needle biopsy grading in patients with well-differentiated prostate cancer.

OBJECTIVES: Gleason grade from prostate needle biopsy (PNB) specimens is important in guiding therapeutic decision making in patients with localized prostate cancer. Recent data from our institution suggest a significant discordance between Gleason grading from PNB versus the actual pathologic grade at radical prostatectomy (RRP). Of most concern is that a substantial proportion of patients with Gleason score of 6 or less from PNB actually have Gleason score of 7 or more at RRP. Under classic measurement theory, one useful way to improve the reliability of an inherently unreliable test is to repeat it. We investigated this strategy in an effort to reduce undergrading errors. METHODS: The control group of patients (n = 51) from our neoadjuvant androgen deprivation protocol was used as the test (two-biopsy) group in this study. These patients underwent two separate PNBs before RRP. We used the highest Gleason score from the two biopsies in these patients and compared the error rates with a concurrent group of patients treated at our institution (n = 226) who had only one set (single-biopsy group) of prostate biopsies. All pathologic slides were reviewed at our institution. Any PNB grade of 6 or less that was scored as 7 or more on final pathology was considered significant. RESULTS: Mean age, prostate-specific antigen levels, and stage distribution were not significantly different between these two groups. In the single-biopsy group, 165 patients had PNB Gleason score of 6 or less. Of these patients, 63 (38%) had final pathologic grade of 7 or more. In the two-biopsy group, 37 patients had PNB Gleason score of 6 or less. Of these patients, only 7 (19%) had final pathologic grade of 7 or more (P = 0.04). CONCLUSIONS: Prostate rebiopsy minimizes the inherent unreliability of PNB derived grade and should be considered for patients in whom watchful waiting or nomogram-based therapy has been selected.

Prognostic significance of prostate-specific antigen in stage T1c prostate cancer treated by radical prostatectomy.

OBJECTIVES: Increasingly, nonpalpable prostate-specific antigen (PSA)-detected (Stage T1c) tumors are being treated with curative intent. Presently, only limited information is available regarding pathologic findings correlated with preoperative PSA levels. Herein, we report the characteristics of Stage T1c tumors in a contemporary surgical series. METHODS: Clinical and pathologic results in 107 patients with Stage T1c tumors treated with radical prostatectomy were compared with those in 300 patients with palpable (Stage T2) tumors. Multivariate analysis was performed to determine which clinical variables independently predicted pathologic staging. RESULTS: Stage T1c tumors were equivalent to Stage T2 tumors with respect to organ-confined and margin-positive rates. PSA level was the strongest independent predictor of extracapsular and margin-positive rates (P = 0.003). The absence of palpability was not a significant predictor of pathologic outcome. Significantly higher rates of organ- and specimen-confined disease were seen in patients with PSA levels less than 10.0 ng/mL, particularly less than 7.0 ng/mL. Patients with serum PSA levels greater than 20 ng/mL were at high risk for positive margins (relative risk 5.42, P < 0.001). CONCLUSIONS: Stage T1c tumors represent a heterogeneous group of cancers. These tumors are pathologically similar to Stage T2 tumors, and patients should be offered similar treatment options. PSA level was the strongest predictor of pathologic stage, irrespective of tumor palpability. These results suggest that efforts directed toward identifying cancers, including nonpalpable tumors, in patients with early PSA elevations may result in improved rates of organ-confined disease. The impact of treatment on Stage T1c tumors remains to be defined.

The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results.

OBJECTIVES: The use of neoadjuvant chemotherapy prior to definitive surgery has been firmly established in other areas of oncology, most notably in the treatment to testis and Wilm's tumors. The use of neoadjuvant androgen deprivation therapy (ADT) in conjunction with radical prostatectomy remains a source of controversy. We have conducted phase II and phase III studies to assess the effects of 3 months of preoperative ADT (goserelin and flutamide) on the pathologic staging and postsurgery prostate-specific antigen (PSA) relapse rate. We also reviewed the data confirming the understaging of clinically localized prostatic cancer and the experimental data providing the conceptual support for ADT. METHODS: We report the results of 141 patients, Stage T0-T0, in a Phase II study with concurrent, nonrandomized controls (N = 72) versus a treatment arm (N = 69) of men receiving 3 months of ADT with 3.6 mg goserelin for 28 days and 750 mg flutamide daily. We also report the interim results in 114 men participating in a prospective, randomized study of ADT versus surgery alone. RESULTS: The 69 patients who received 3 months of goserelin and flutamide followed by radical prostatectomy had a pathologic organ-confined cancer rate of 74%, versus 48% in the control group who received no ADT prior to surgery. The margin-positive rate was 10% in the ADT group versus 33% in the control group. In an interim analysis of 114 patients (59 ADT, 55 control), the organ-confined and margin-positive rates were 73% and 17% in the ADT group versus 56% and 36% in the control arm, respectively. The PSA disease-free rate at a mean follow-up of 28.6 months (range 6.2 to 49.5 months) was 89% in the ADT-treated patients (N = 98) and 84% in the control patients (N = 96). There was no statistical difference demonstrated between the arms with respect to biochemical failure. CONCLUSIONS: While the pathologic staging of tumors following ADT treatment was improved compared with surgical controls, to date the PSA disease-free survival rates are similar. Patients with residual extracapsular (P3) disease after ADT manifest an increased PSA failure rate compared with those with P3 tumors treated by surgery alone. This suggests that ADT may identify a subset of patients with aggressive tumors that may be candidates for additional therapeutic interventions even before PSA failure occurs.

Correlation between Gleason score of needle biopsy and radical prostatectomy specimen: accuracy and clinical implications.

PURPOSE: Despite the reliability of Gleason grading with respect to the same specimen, the correlation between the biopsy and prostatectomy specimen is less well defined. We compared the accuracy of Gleason grading of biopsies in predicting histological grading of radical retropublic prostatectomy specimens. MATERIAL AND METHODS: Gleason scores of 18 gauge needle biopsies were compared to those of radical retropublic prostatectomy specimens in 226 consecutive patients. In addition to comparing numeric discrepancies, differences between biopsy and specimen Gleason scores of 2 or more and a change in group from Gleason scores 2 to 4, 5 to 7 or 8 to 10 were evaluated by kappa testing, as well as any change in group from Gleason scores 2 to 4, 5 and 6, 7 and 8 to 10. RESULTS: The biopsy score was identical to the specimen score in 31% of cases, while 26% were discrepant by 2 or more Gleason scores. Overall, 54% of biopsies were under graded, while 15% were over graded. If only cases in which discrepancies of 2 or more Gleason scores and a change in group were considered, there was good overall agreement (kappa 0.468, accuracy 80%). Among the cases with any change in group, the accuracy was only 46% with poor agreement (kappa 0.153). CONCLUSIONS: Overall, the reliability of Gleason grading of needle biopsies in predicting final pathology was good. However, the limitations of Gleason grading based on biopsy should be considered when discussing treatment options and comparing results based on biopsy data.

Upper tract tumors in patients with primary bladder cancer followed for 15 years.

PURPOSE: We evaluated the long-term incidence of upper tract tumors in patients with primary superficial bladder cancer. MATERIALS AND METHODS: A total of 86 patients with stages Ta, T1 and Tis bladder tumors, who were entered into a prospective trial of bacillus Calmette-Guerin between 1978 and 1981, was followed for 15 years or longer. RESULTS: Of the 86 patients 18 (21%) had upper tract tumors after a median interval of 7.3 years (range 1 to 15). Tumors occurred within 5 years of followup in 6 cases, between 5 and 10 years in 7, and between 10 and 15 years in 5. The majority of cancers were invasive and 7 patients died of upper tract tumors. CONCLUSIONS: Patients with primary bladder tumors are at risk for upper urinary tract disease for up to 15 years, which suggests the need for lifelong regular upper tract monitoring in these cases.

Endo-rectal coil magnetic resonance imaging in clinically localized prostate cancer: is it accurate?

PURPOSE: We assessed the staging accuracy of endo-rectal coil magnetic resonance imaging (MRI) in patients with clinically localized prostate cancer. MATERIALS AND METHODS: In a prospective study 56 consecutive patients underwent endo-rectal coil MRI before scheduled surgery. The ability of MRI to identify tumor involvement of the periprostatic soft tissue, seminal vesicles and pelvic lymph nodes was assessed by comparison with final pathological stage. RESULTS: Specificity of MRI was relatively high (84% for periprostatic soft tissue, 93% for seminal vesicles and 91% for pelvic lymph nodes) and sensitivity was low (22, 23 and 0%, respectively). Accuracy was 64% for identification of periprostatic soft tissue invasion, 77% for seminal vesicle invasion and 86% for pelvic lymph node metastases. Had we excluded from surgery patients with MRI evidence of extraprostatic disease our organ confined disease rate would have improved by 16.6%. However, this improvement would have been obtained at the expense of incorrectly excluding from surgery 21% of our patients with pathologically organ confined disease because of false-positive MRI predictions. CONCLUSIONS: Endo-rectal coil MRI is not sufficiently accurate to influence the treatment of patients with clinically localized prostate cancer. Therefore, we advise against routine use of this imaging modality in staging such cases.