Abstract Context. —Minimal volume prostatic adenocarcinoma (defined as involving less than 5% of biopsy tissue) is diagnosed increasingly today because of successful cancer screening. We previously described the diagnostic category called atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy, present in about 2.5% of routine prostatic needle biopsy specimens. Objective. —To establish the criteria enabling a distinction between ASAP and cancer. Design. —We prospectively evaluated clinical and histologic findings from all 319 patients consecutively diagnosed as having ASAP or minimal cancer by prostatic needle biopsy in a consultation service. Seventeen histopathologic features were assessed. Results. —Fifty-six patients (18%) had ASAP, and 100 (31%) had minimal cancer; the remaining 163 (51%) had benign diagnoses, high-grade prostatic intraepithelial neoplasia, or larger amounts of cancer. The mean age of patients with ASAP did not differ from that of patients with minimal cancer (64.2 years vs 63.3 years; P = .65). In 10 of 17 histopathologic findings, ASAP differed significantly from minimal cancer. Among architectural findings, ASAP foci averaged 0.4 vs 0.8 mm ( P < .0001) and comprised a mean of 11 vs 17 acini ( P < .0001). Infiltrative growth occurred in 75% of ASAP foci and 100% of minimal cancers ( P < .0001). Among cytologic findings, ASAP was significantly less likely than cancer to have mitotic figures (0% vs 10%, respectively; P < .01) or prominent nucleoli in at least 10% of cells (55% vs 100%, respectively; P < .0001) and showed more frequent nuclear hyperchromasia (44% vs 9%, respectively; P < .0001) and less nuclear enlargement ( P = .0002). Luminal blue mucin secretions were less common in ASAP than cancer (6% vs 33%, respectively; P < .0001), but eosinophilic granular secretions and crystalloids were about equally frequent. Concomitant high-grade prostatic intraepithelial neoplasia was present in 23% of ASAP cases and 57% of cancers ( P < .0001). Moderate-to-severe atrophy confounded 59% of cases with ASAP and 35% of cancers ( P = .003); both ASAP foci and cancer were associated with inflammation in about a quarter of cases. In each case with ASAP, we stratified our level of suspicion among 3 categories (favor benign, uncertain, and favor carcinoma). As suspicion increased so did the mean nuclear enlargement and percentage of cases with infiltrative growth and nuclear hyperchromasia (all P < .05). Conclusions. —These criteria, which differ significantly between ASAP and minimal volume cancer, can help to separate patients for whom a second biopsy is recommended from candidates for prostatectomy or other therapy.
Utility of Pathology Imagebase for standardisation of prostate cancer grading
AimsDespite efforts to standardise grading of prostate cancer, even among experts there is still a considerable variation in grading practices. In this study we describe the use of Pathology Imagebase, a novel reference image library, for setting an international standard in prostate cancer grading.Methods and resultsThe International Society of Urological Pathology (ISUP) recently launched a reference image database supervised by experts. A panel of 24 international experts in prostate pathology reviewed independently microphotographs of 90 cases of prostate needle biopsies with cancer. A linear weighted kappa of 0.67 (95% confidence interval = 0.62–0.72) and consensus was reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89. The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed considerable disagreement. Once a two‐thirds majority was reached, images were moved automatically into a public database available for all ISUP members at www.isupweb.org. Non‐members are able to access a limited number of cases.ConclusionsIt is anticipated that the database will assist pathologists to calibrate their grading and, hence, decrease interobserver variability. It will also help to identify instances where definitions of grades need to be clarified.
Combining Prostate Specific Antigen with Cancer and Gland Volume to Predict More Reliably Pathological Stage: The Influence of Prostate Specific Antigen Cancer Density
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.
Predicting Cancer Progression in Patients With Stage T1 Bladder Carcinoma
PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P = .037). The 5-year progression-free survival rate for patients with depth of invasion of ≥ 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P = .009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.
Baseline Prostate Atrophy is Associated with Reduced Risk of Prostate Cancer in Men Undergoing Repeat Prostate Biopsy
High Expression of Somatostatin Receptors and Messenger Ribonucleic Acid for Its Receptor Subtypes in Organ-Confined and Locally Advanced Human Prostate Cancers1
To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (Kd) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8–10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.
The Effect of Dutasteride on the Usefulness of Prostate Specific Antigen for the Diagnosis of High Grade and Clinically Relevant Prostate Cancer in Men With a Previous Negative Biopsy: Results From the REDUCE Study