Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer.

OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale. MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed. RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001). CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.

Prediction of percent Gleason grade 4/5 by multiple core biopsies.

OBJECTIVE: To evaluate whether percent Gleason grade 4/5 (i.e. the proportion of a tumor occupied by high-grade cancer) can be predicted by multiple needle biopsies. MATERIAL AND METHODS: In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed and cancer lengths measured. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and tumor volume measured planimetrically. Gleason scores and percent Gleason grade 4/5 were assessed for both biopsy and prostatectomy specimens. RESULTS: Percent Gleason grade 4/5 in prostatectomy specimens was predicted correctly in 34% of cases and within 10%, 20% and 30% in 55%, 64% and 73% of cases, respectively. Biopsies had a sensitivity, specificity and accuracy for Gleason grade 4/5 of 62%, 87% and 69%, respectively. Positive and negative predictive values were 93% and 45%, respectively. The weighted kappa value for agreement was slightly higher for Gleason score (0.685) than for percent Gleason grade 4/5 (0.573). The univariate correlation for percent Gleason grade 4/5 in biopsies and the main tumor was r=0.62, r(2)=0.39 (p<0.001). In univariate logistic regression, percent Gleason grade 4/5 on biopsies predicted the presence of any Gleason grade 4/5 cancer in the main tumor (p=0.009). CONCLUSIONS: Gleason grade 4/5 in prostatectomy specimens correlates with findings in preoperative biopsies. Whether this measure will be used in routine practice remains to be seen.

Prediction of the volume of large prostate cancers by multiple core biopsies.

OBJECTIVE: To evaluate whether large-volume prostate cancers can be predicted by means of multiple needle biopsies. MATERIAL AND METHODS: In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed, the length of the cancer measured and the percentage cancer length calculated. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and the tumor volume was measured planimetrically. The predictive values of the number and percentage of cores positive for cancer, cancer length and percentage cancer length were calculated for tumor volumes of >4, >6 and >8 ml. RESULTS: Using univariate logistic regression, cancer length and percentage cancer length predicted tumor volumes of >4 (p<0.001), >6 (p<0.001) and >8 ml (p<0.05). These measures were better predictors of tumor volume than the number and percentage of cores positive for cancer. A biopsy cancer length of > or =30 mm and a percentage cancer length of > or =25% predicted a tumor volume of >4 ml in 95% and 93% of cases, respectively. For tumor volumes of >6 or >8 ml, predictive values were lower. Tumor volumes of <2 and <4 ml were found in 13% and 35%, respectively of men with as many as six positive cores, indicating that the number of positive cores was less useful as a predictor of tumor volume than the cancer length. CONCLUSIONS: Cancer length and percentage cancer length are significant predictors of large tumor volumes. It is recommended that the linear extent of cancer in prostate biopsies should be reported by the pathologist.

The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer.

OBJECTIVE: In a previous study, we mapped the ploidy heterogeneity of prostate cancer using flow cytometry in 676 tumor samples from 50 radical prostatectomy specimens. Ploidy heterogeneity was common (42% of tumors) and was found in all non-diploid tumors. The volume of non-diploid tumor was estimated and found to predict extra-prostatic extension and seminal vesicle invasion. The aim of this study was to evaluate the impact of tumor heterogeneity on preoperative ploidy assessment. MATERIAL AND METHODS: In 50 men at least six core biopsies were taken before prostatectomy. Sections from biopsies with cancer were Feulgen-stained for image cytometry. After exclusion of biopsies with insufficient material, 123 histograms from 48 men (mean 2.6; range 1-7) remained for analysis. RESULTS: In 32 men, biopsies were diploid. In 16 men, at least one biopsy was non-diploid (14 tetraploid, two aneuploid) and 10 of them also had diploid biopsies. In 34 men (71%), the prostatectomy specimens were correctly predicted as being either diploid (48%) or non-diploid (23%). The sensitivity and specificity of biopsies for predicting non-diploid cancer were 55% and 82%, respectively, and the positive and negative predictive values were 69% and 72%, respectively. The ploidy status of tumors with and without ploidy heterogeneity was correctly predicted in 55% and 82% of cases, respectively (p=0.04). Biopsies underestimated ploidy in 9/20 tumors (45%) with heterogeneous ploidy status. Underestimation mainly occurred when one or two cores were analyzed. CONCLUSIONS: Preoperative prediction of the ploidy status of prostate cancer is hampered by tumor heterogeneity. Analysis of multiple biopsies is important for correct preoperative ploidy estimation.

No increased prostate cancer incidence after negative transrectal ultrasound guided multiple biopsies in men with increased prostate specific antigen and/or abnormal digital rectal examination.

PURPOSE: We investigated the incidence of prostate cancer after negative transrectal ultrasound (TRUS) guided multiple biopsies. Our secondary aim was to calculate the sensitivity of the extended protocol used. MATERIALS AND METHODS: A cohort of 547 men with elevated prostate specific antigen and/or abnormal digital rectal examination but with results negative for prostate cancer on a mean of 9 TRUS guided biopsies was followed through record linkage to the national cancer Registry. The observed number of prostate cancers was compared with the expected number during the same calendar period in an age matched male population to determine the standardized incidence ratio. The sensitivity of TRUS with multiple biopsies after 5 years of followup was calculated. Relative survival was estimated if there was an excess death rate due to undiagnosed prostate cancer. RESULTS: We found 11 men diagnosed with prostate cancer. The expected number in the age standardized male population was 15, resulting in a standardized incidence ratio of 0.8 (95% CI 0.4 to 1.2). Five-year sensitivity of the extended protocol of TRUS guided biopsies was 95.2% (95% CI 93.5 to 96.4) and relative survival was more than 100%, indicating a selection of men deemed candidates for curative treatment. CONCLUSIONS: Men with clinical suspicion of prostate cancer who are examined by an extended protocol of TRUS guided biopsies negative for cancer do not have an increased incidence of prostate cancer within 6 years compared with an age matched male population. Five-year sensitivity of this protocol was high.