Higher Cancer Volume Research Articles

Thyroid Imaging Reporting and Data System Risk Stratification of Thyroid Nodules: Categorization Based on Solidity and Echogenicity.

Although ultrasonography (US) has an essential role in assessing the malignancy risk of thyroid nodules, a malignancy risk-stratification system has not been established. The purpose of this study was to develop a clinically feasible US risk-stratification system--the Thyroid Imaging Reporting and Data System (TIRADS)--primarily based on the solidity and echogenicity of thyroid nodules. From January 2010 to May 2011, a total of consecutive 2000 thyroid nodules (≥ 1 cm) with final diagnoses were enrolled from the database of low and high cancer volume institutions (1000 nodules from each institution). For the development of TIRADS, the type and predictive value of US predictors in the groups categorized by solidity and echogenicity were analyzed, and the US predictors were integrated and categorized according to the malignancy risk. The suspicious US features of microcalcification, taller than wide shape, and spiculated/microlobulated margin were independently predictive of malignancy in the solid or hypoechoic nodule group (p < 0.001, respectively). Meanwhile, only microcalcification was independently predictive of malignancy in the partially cystic nodule group (p = 0.006), and microcalcification and spiculated/microlobulated margin were independently predictive of malignancy in the iso- and hyperechoic nodule group (p = 0.002 and p = 0.015, respectively). Although the presence of any suspicious US features had a high malignancy risk in the group of solid hypoechoic nodules, it had an intermediate malignancy risk in the group of partially cystic or iso- and hyperechoic nodules. The malignancy risk of thyroid nodules was stratified into five TIRADS categories by integrating the type and predictive values of US predictors based on solidity and echogenicity. The malignancy risk of thyroid nodules can be stratified by TIRADS according to US patterns by combining solidity, echogenicity, and suspicious US features. The proposed risk-stratification system based on solidity and echogenicity will be useful for risk stratification and management decision of thyroid nodules.

Understanding the Performance of Active Surveillance Selection Criteria in Diverse Urology Practices

We used data from MUSIC (Michigan Urological Surgery Improvement Collaborative) to evaluate the performance of published selection criteria for active surveillance in diverse urology practice settings. For several active surveillance guidelines we calculated the proportion of men meeting each set of selection criteria who actually entered active surveillance, defined as the sensitivity of the guideline. After identifying the most sensitive guideline for the entire cohort we compared demographic and tumor characteristics between patients who met this guideline and entered active surveillance, and those who received initial definitive therapy. Of 4,882 men with newly diagnosed prostate cancer 18% underwent active surveillance. When applied to the entire cohort, the sensitivity of published guidelines ranged from 49% in Toronto to 62% at Johns Hopkins. At apractice level the sensitivity of Johns Hopkins criteria varied widely from 27% to 84% (p <0.001). Compared with men undergoing active surveillance, those meeting Johns Hopkins criteria who received definitive therapy were younger (p<0.001) and more likely to have a positive family history (p = 0.003), lower prostate specific antigen (p <0.001), a greater number of positive cores (2 vs 1) on biopsy (p <0.001) and a higher cancer volume in positive core(s) (p = 0.002). The sensitivity of published active surveillance selection criteria varies widely across diverse urology practices. Among patients meeting the most stringent criteria those who received initial definitive therapy had characteristics suggesting greater cancer risk, underscoring the nuanced clinical factors that influence treatment decisions.

Urinary TMPRSS2:ERG and PCA3 in an Active Surveillance Cohort: Results from a Baseline Analysis in the Canary Prostate Active Surveillance Study

Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2:ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort. Urine was collected after digital rectal examination prospectively as part of the multi-institutional Canary Prostate Active Surveillance Study (PASS). PCA3 and TMPRSS2:ERG levels were analyzed in urine collected at study entry. Biomarker scores were correlated to clinical and pathologic variables. In 387 men, both PCA3 and TMPRSS2:ERG scores were significantly associated with higher volume disease. For a negative repeat biopsy, and 1% to 10%, 11% to 33%, 34% or more positive cores, median PCA3, and TMPRSS2:ERG scores increased incrementally (P < 0.005). Both PCA3 and TMPRSS2:ERG scores were also significantly associated with the presence of high-grade disease. For a negative repeat biopsy, Gleason 6 and Gleason ≥7 cancers, the median PCA3, and TMPRSS2:ERG scores also increased incrementally (P = 0.02 and P = 0.001, respectively). Using the marker scores as continuous variables, the ORs for a biopsy in which cancer was detected versus a negative repeat biopsy (ref) on modeling was 1.41 (95% CI: 1.07-1.85), P = 0.01 for PCA3 and 1.28 (95% CI: 1.10-1.49), P = 0.001 for TMPRSS2:ERG. For men on active surveillance, both PCA3 and TMPRSS2:ERG seem to stratify the risk of having aggressive cancer as defined by tumor volume or Gleason score.

Transitional Zone and Anterior Peripheral Zone of the Prostate

Introduction: Prognostically significant prostatic adenocarcinomas (PAC) may pose diagnostic problems if they were localized in the anterior peripheral zone (APZ) or transitional zone (TZ). Materials and Methods: 108 cases of PAC were reviewed along with serum PSA and TRUS biopsies. The PACs were divided into 22 TZ, 17 APZ and 69 posterior peripheral zone (PPZ) PACs according to the location of the main tumor mass in the TZ and anterior or posterior half of the peripheral zone in the radical prostatectomy (RP) specimens. Results: In comparison with PPZ PAC, TZ PAC had a higher cancer volume in RP specimens (4 ± 2.1 vs. 2.5 ± 1.7 cm³, p < 0.01), a higher serum PSA (16.5 ± 9.8 vs. 8.4 ± 4.5 µg/l, p < 0.001), a biopsy with a small cancer volume (3.8 ± 2.1 vs. 11.8 ± 9.4 mm, p < 0.005), and a lower Gleason’s score (4.8 ± 2.1 vs. 6.5 ± 1.7). APZ PAC was characterized by the cancer volume in RP and biopsy and PSA intermediate between those of TZ and PPZ PAC. Among 24 PACs with a total cancer core length of <3 mm, 19 cases were from the TZ and APZ groups and also had a higher cancer volume and PSA than those from the PPZ group (2.9 ± 1.8 vs. 1.5 ± 1.3 and 13.7 ± 8.3 vs. 9.6 ± 4 µg/l, respectively). Furthermore, there was a better correlation coefficient (r²) of tumor volume in the biopsy and RP for PPZ than for all zones PAC (r² = 0.75 vs. 0.29). TZ and APZ carcinomas were associated with extension or satellite nodules of PAC in the PPZ that may be diagnosed with biopsies. These PACs were associated with positive anterior resection margin due to extracapsular extension of the carcinoma or intracapsular dissection in 6 and 5 cases respectively. Conclusions: TZ and APZ PACs accounted for the poor correlation between the tumor volume in the biopsy and the RP, and were associated with positive anterior resection margins. One core biopsy with a total cancer core length of <3 mm and PSA >10 µg/l are suspicious for TZ and APZ PCA in patients with undetectable tumors with DRE or TRUS. Clinically insignificant PACs tend to be associated with cancer core <3 mm and PSA <10 µg/l.

Telomerase activity in prostate sextant needle cores from radical prostatectomy specimens

Human telomerase acts to maintain functioning telomeres, which are required for cellular immortality and very likely for cancer progression. Telomerase activity is present in about 85% of human cancers tested, but it has not been found in most human somatic cells and tissues. We used the Telomeric Repeat Amplification Protocol to perform telomerase activity assays on sextant needle core samples obtained from 35 freshly excised radical retropubic prostatectomy specimens. Similar assays were done on prostatic tissues obtained by means of other urologic procedures from 8 patients without prostate cancer. Telomerase activity was found in one or more specimens from 32 of 35 prostate cancer patients (91%), but was not detectable in all biopsy specimens from 7 of 8 cancer-free patients (88%). Further analysis showed that cancers more poorly differentiated, with higher Gleason scores, were always associated with a higher rate of telomerase detection and stronger telomerase activity. Moreover, comparison of telomerase activity in needle core samples with the volume of cancer in surrounding tissue as observed on corresponding histologic slides showed that stronger activity was positively correlated with a higher cancer volume. Prognostic indicators of prostate cancer and the expression of telomerase appear to be linked. The presence of telomerase activity in prostate tissue may aid in the detection of prostate cancer and produce additional prognostic information.

RETRACTED: Prostate cancer screening in the Tyrol, Austria: experience and results

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

Prostate Cancer Screening in Tyrol, Austria: Experience and Results

Background: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate-specific antigen (PSA) and percent free PSA as the initial test. Methods: The twelve projects studied included: (1) a mass screening study using PSA as the initial test in 21,079 volunteers; (2) an investigation of the usefulness of normal and age-referenced PSA cut-offs in 1,618 men; (3) a PSA-based screening study of 2,272 asymptomatic blood donors; (4) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative digital rectal examination findings; (5) determination of percent free PSA in one retrospective and two prospective studies to determine the appropriate cutpoints for percent free PSA; (6) evaluation of the diagnostic benefit of PSA transition zone density in 308 screening volunteers; (7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma in 1,543 men undergoing transurethral resection of the prostate; (8) an evaluation of the changes in total PSA and pathologic stages in radical prostatectomy over 5 years in a PSA-based mass screening program; (9) a study evaluating the probability of having prostate cancer given the patient’s age, total PSA and digital rectal examination findings; (10) an evaluation of the correlation between preoperative predictors and pathologic features in radical prostatectomy specimens; (11) an investigation of the correlation of total PSA with pathologic stage and tumor volume in patients undergoing radical prostatectomy with low PSA cut-off level, and (12) a study whether age has an impact on the extension of prostate cancer. Results: (1) of the 21,079 volunteers, 1,618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies were positive for prostate carcinoma and 135 underwent radical prostatectomy. Ninety-five were found to be organ-confined. (2) A PSA cut-off of 2.5 ng/ml in men aged 45–49 years and of 3.5 ng/ml in men aged 50–59 years resulted in an 8% increase in the detection rate of organ-confined disease. (3) Of the 2,272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined tumor in all but 8 men. (4) Ninety-eight of 340 men had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transition zone only. (5) In the retrospective study, receiver-operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated PSA levels <10.0 ng/ml were further evaluated and 37 prostate carcinomas were detected. By using a % free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/ml and a % free PSA <18% were further evaluated and 27 (22.5%) were found to have prostate carcinomas. (6) Receiver-operating characteristic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of >22 ng/ml/cm³ as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. (7) In the prescreening era the incidence of T1a grade 1 and 2 carcinomas was 3.1% and the incidence of T1a grade 3 and T1b carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. (8) The rate of organ-confined tumors increased from 28.7% in 1993 to 65.7% in 1997. (9) In this evaluation a new approach to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cutpoint was developed. (10) High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. (11) In this evaluation all of the 95 patients with PSA levels <3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. (12) The results of this evaluation suggest that older men have larger tumor volumes compared to younger men with the same PSA levels. Conclusions: These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ-confined and potentially curable prostate cancer. Percent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.