Biopsy Criteria for Determining Appropriateness for Active Surveillance in the Modern Era

doi:10.1016/j.urology.2013.12.054

Urology

Volume 83, Issue 4, April 2014, Pages 869-874

https://doi.org/10.1016/j.urology.2013.12.054 Get rights and content

Objective

To evaluate algorithms to predict insignificant prostate cancer at radical prostatectomy (RP).

Methods

Five hundred and fifty men (410 Caucasian, 100 African American [AA], and 40 others) with prostate-specific antigen (PSA) level <10 ng/dL, T1c, 12-core biopsy, and biopsy Gleason score 3 + 3 = 6 were categorized into training and validation sets. Six biopsy algorithms were tested for predicting insignificant (0.5 cm³, organ confined, and Gleason score ≤6) cancer at RP. Cancers incorrectly predicted to be insignificant were ranked into 4 groups of increasing aggressiveness.

Results

Original (Gleason score ≤6, PSA density ≤0.15, ≤2 positive cores, and maximum core involvement ≤50%) and modified Epstein criteria (Gleason score ≤6, PSA density ≤0.15, ≤2 positive cores, and unilateral cancer) had the highest negative predictive values—correct classification of insignificant cancer. Among cancers predicted to be insignificant in Caucasians, 29.9% cases using the original and 27% cases using the modified Epstein criteria had significant cancer at RP. However, more adverse findings at RP were misclassified as insignificant in only 3.5% and 2.2% of cases using the original and modified Epstein criteria, respectively. Of cancers predicted insignificant in AA men, 54.1% cases using the original and 51.6% cases using the modified Epstein criteria were misclassified as insignificant. Dominant anterior tumors were seen in 117 Caucasian (28.5%) and 44 AA men (44%).

Conclusion

The Epstein criteria maintain their accuracy in the modern era with extended biopsy sampling. The negative predictive values are lower in AA men, in part due to higher frequency of anterior tumors, where multiparametric magnetic resonance imaging should be recommended in AAs considering surveillance.

Section snippets

Materials and Methods

Consecutive African American (AA) men (n = 100) with preoperative serum PSA level <10 ng/mL, biopsy Gleason score ≤6, stage T1c, and 12-core sampling who underwent radical prostatectomy (RP) from 2004 to 2012 were selected. Four hundred and fifty consecutive men (410 Caucasian and 40 others) with identical criteria were selected from 2010 to 2012. Although a slightly different period from when AAs were selected to obtain a large number of AA men for analysis, clinical and pathologic assessment

Results

Preoperative data are summarized in Table 2 and largely showed no difference between training and validation cohorts. We first tested in a multivariate regression analysis the negative predictive value (NPV) of PSA (P = .02) and PSAD (P <.001) because they are highly related, by comparing which measure had the fewest and least advanced cases misclassified as insignificant. Because PSAD was superior to PSA, PSAD was included in all algorithms, a similar finding to our original study.¹ Caucasian

Comment

The crux of AS programs is to identify cancers, which, if left untreated, would likely not cause harm to patients. A complicating factor in developing algorithms to predict insignificant cancer is that there is a spectrum of severity in cases defined as “significant cancer.” What is universally accepted as insignificant prostate cancer is organ-confined, Gleason score 3 + 3 = 6 disease with dominant tumor nodule volume ≤0.5 cm³.¹ The problem with this as the sole classification, is that, for

Conclusions

The Epstein algorithm, either the original or modified criteria that we have now adopted, maintains its accuracy in the modern era of prostate cancer with extended biopsy sampling. Approximately one-half of the tumors incorrectly predicted to be insignificant were anteriorly located, which may not be sampled by a standard 12-core prostate biopsy. Because AAs have more anterior tumors that are hard to sample, multiparamteric MRI should be recommended in AAs considering surveillance. In assessing

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Cited by (92)

Diagnostic pathway of the biopsy-naïve patient suspected for prostate cancer: Real-life scenario when multiparametric Magnetic Resonance Imaging is not centralized
2021, Progres en Urologie
We aimed to compare the pathway including multi-parametric Magnetic Resonance Imaging (mpMRI) versus the one without mpMRI in detection of prostate cancer (PCa) when mpMRI is not centralized.
January 2019-March 2020: prospective data collection of trans-perineal prostate biopsies. Group A: biopsy-naïve patients who underwent mpMRI (at any institution) versus Group B: patients who did not. Within Group A, patients were stratified into those with negative mpMRI (mpMRI-, PIRADS v2.1 = 1-3, with PSA density < 0.15 if PIRADS 3) who underwent standard biopsy (SB), versus those with positive mpMRI (mpMRI+, when PIRADS 3–5, with PSA density > 0.15 if PIRADS 3) who underwent cognitive fusion biopsy.
Two hundred and eighty one biopsies were analyzed. 153 patients underwent mpMRI (Group A). 98 mpMRI+ underwent fusion biopsy; 55 mpMRI- underwent SB. 128 Group B patients underwent SB. Overall PCa detection rate was 52.3% vs. 48.4% (Group A vs. B, P = 0.5). Non-clinically-significant PCa was detected in 7.8 vs. 13.3% (Group A vs. B, P = 0.1). Among the 98 mpMRI+ Group A patients only 2 had non clinically-significant disease. In 55 mpMRI- patients who underwent SB, 10 (18.2%) had clinically-significant PCa. Prostate volume predicted detection of PCa. In Group B, age and PSA predicted PCa. Sensitivity of mpMRI was 75.0% for all PCa, 85.3% for clinically-significant PCa.
Higher detection of PCa and lower detection of non-clinically-significant PCa favored mpMRI pathway. A consistent number of clinically-significant PCa was diagnosed after a mpMRI-. Thus, in real-life scenario, mpMRI- does not obviate indication to biopsy when mpMRI is not centralized.
3.
Nous avons comparu la voie comprenant l’imagerie par résonance magnétique multiparamétrique (IRM-mp) et celle sans IRM-mp pour la détection du cancer de la prostate (CP).
Janvier 2019–mars 2020 : récolte prospective de données de biopsies prostatiques transpérineales. Groupe A : patients sans biopsie ayant subi une IRM-mp ; Groupe B : patients qui ne l’ont pas subi. Dans le Groupe A, les patients ont été divisés entre ceux avec IRM-mp négatif (IRM-mp-), candidats pour biopsie standard (BS) et ceux avec IRM-mp positif (IRM-mp + ) candidats pour biopsie de fusion cognitive (BF).
Cent cinquante trois patients ont subi une IRM-mp (Groupe A). 98 avaient une IRM-mp+ et ont subi une BF ; 55 avaient une IRM-mp- et ont subi une BS. 128 patients du Groupe B ont subi une BS. Le taux global de détection du CP était de 52,3 % vs 48,4 % (Groupe A vs B, p = 0,5). Un CP non cliniquement significatif a été détecté dans 7,8 vs 13,3 % (Groupe A vs B, p = 0,1). Parmi les 98 patients du Groupe A IRM-mp+, seulement 2 avaient un CP non cliniquement significatif. Chez 55 patients avec IRM-mp-, qui ont subi une BS, 10 (18,2 %) avaient un CP cliniquement significatif. Dans le Groupe B, l’âge et le PSA prédisaient le CP. La sensibilité de l’IRM-mp était 75,0 % pour tous les CP et 85,3 % pour les CP cliniquement significatifs.
Un nombre important de CP cliniquement significatifs a été diagnostiqué après une IRM-mp négative. Dans un contexte de vie-réelle, une IRM-mp négative ne doit pas empêcher la réalisation d’une biopsie de la prostate.
3.
A Systematic Review for Health Disparities and Inequities in Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis
2021, Academic Radiology
Multi-parametric Magnetic Resonance Imaging (mpMRI) is a novel procedure recommended by the American Urological Association for Prostate Cancer (PCa) diagnosis. In radiology, differences in utilization of expensive screening techniques are described but never reviewed for mpMRI. Thus, our article aims at summarizing disparities relating to the expensive yet revolutionary mpMRI in United States men with PCa while highlighting needed research areas.
Eligible articles were gathered via PubMed query, referred publications known to the authors or from the reference lists of the identified publications. We excluded studies that didn't specifically evaluate mpMRI technique, weren't conducted in the United States, or didn't directly assess the relationship between disparities and mpMRI. No date restrictions were applied, resulting articles were published through 2020.
Out of 80 publications, 17 were selected. Two unique themes were identified: 1) disparities in mpMRI utilization, and 2) performance. While demographic factors such as race, age and socioeconomic status played a significant role in utilization, mpMRI demonstrated equal and sometimes superior performance in AAs.
Our findings illustrate the importance of disparity awareness in PCa mpMRI and highlight the need to examine additional mpMRI disparities across other races and social determinants. A new area of inequity in PCa was theoretically illustrated, as lower utilization of mpMRI was detected in a group that could potentially benefit from it the most. Major limitation was the selected search terms. Our review is unique as disparities related to mpMRI were found to be multilayered, affecting utilization and performance. Continued research is needed to discover additional areas in efforts to reduce disparity gaps related to mpMRI and PCa.
Prediction of Organ-confined Disease in High- and Very-high-risk Prostate Cancer Patients Staged with Magnetic Resonance Imaging: Implications for Clinical Trial Design
2021, European Urology Focus
Citation Excerpt :
Many models of preoperative clinical characteristics to predict adverse pathology at radical prostatectomy (RP) or increased risk of poor long-term oncologic outcomes have been described (CAPRA, Epstein criteria, Kattan nomograms, Partin tables, etc.) [1–5].
High-risk (HR) prostate cancer (PCa) is a heterogeneous disease leading to difficulties in designing appropriate inclusion criteria for clinical trials.
To describe clinical predictors of organ-confined disease in HR or very-high-risk (VHR) PCa patients staged with multiparametric magnetic resonance imaging with endorectal coil (mp-MRI-ER).
We reviewed 366 HR/VHR PCa patients who had preoperative mp-MRI-ER, and underwent radical prostatectomy and extended pelvic lymph node dissection between 2006 and 2015.
Radical prostatectomy with preoperative mp-MRI-ER.
We used multivariable logistic regression modeling to assess for associations with ≤ pT2N0 stage and multivariable cox modeling to assess for associations with biochemical failure.
Of 366 patients, 132 had ≤ pT2N0 disease. For the entire cohort, negative staging mp-MRI-ER (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06–2.83, p = 0.03), lower prostate-specific antigen (PSA; OR 0.98, 95% CI 0.97–1.00, p = 0.02), and fewer cores of Gleason ≥8 cancer (OR 0.86, 95% CI 0.79–0.93, p = 0.0002) were associated with ≤pT2N0 disease. In HR patients only, negative mp-MRI-ER (OR 3.41, 95% CI 1.73–6.72, p = 0.0004) and fewer than four cores of Gleason ≥8 disease (OR 3.38, 95% CI 1.20–9.56, p = 0.02) were still associated with ≤pT2N0 disease. Lack of non–organ-confined disease on MRI was associated with superior biochemical recurrence-free survival (p = 0.02). Limitations of this study include lack of a central review or quality control of the MRI reporting.
In HR PCa, negative staging mp-MRI-ER, fewer positive cores of Gleason >8, and lower PSA were significant predictors of pathologic organ-confined disease. Improved prediction of organ-confined disease in HR patients may allow for their inclusion into studies evaluating treatments from which they would otherwise be excluded based solely on their HR status.
In patients with high-risk prostate cancer, prostate magnetic resonance imaging along with other clinical parameters may help determine which patients are likely to have disease confined to the prostate and thus be eligible for clinical trials that they otherwise might be excluded from based on their high-risk status alone.
Gleason score 5 + 3 = 8 (grade group 4) prostate cancer—a rare occurrence with contemporary grading
2020, Human Pathology
Grade Group (GG) 4 prostate cancer includes Gleason scores (GS) 3 + 5 = 8, 4 + 4 = 8, and 5 + 3 = 8. Some studies without pathology re-review of historical cohorts proposed that the presence of pattern 5 worsens prognosis compared to GS 4 + 4 = 8 cancer. We assessed how often historically graded GS 5 + 3 = 8 cancers retain this grade with contemporary grading recommendations. Sixteen prostate biopsies and 24 radical prostatectomies (RP) reported from 2005 to 2019 as GS 5 + 3 = 8 were re-reviewed and graded according to contemporary recommendations. In discrepant cases, an attempt was made to explain the different grading. One (6%) biopsy and 3 (12%) RPs remained GS 5 + 3 = 8 (GG4) after re-review. Two (12%) biopsies remained GG4 but were re-graded as GS 3 + 5 = 8 and 1 (4%) RP was reclassified as GS 4 + 4 = 8 (GG4). Eight (50%) biopsies and 15 (64%) RPs were upgraded to Gleason scores 9–10 (GG5). Five (32%) biopsies and 1 (4%) RPs were downgraded to Gleason score 7 (GG2 and 3). One (4%) RP showed GS 3 + 3 = 6 (GG1) cancer. Data from 2013-current from the 3 institutions were available to assess the incidence of GS 5 + 3 = 8 following re-review of the cases. Out of 14 359 biopsies with cancer and 6727 radical prostatectomy specimens, only 1 case (0.007%) and no cases (0%) were graded as GS 5 + 3 = 8, respectively. Reasons for grading discrepancies included: 1) assigning an overall common grade to separate needle cores or tumor nodules; 2) inclusion of <5% lower grade pattern into grading; and 3) misinterpretation of variant histology and patterns. Challenging patterns were poorly-formed glands, signet ring cell-like features, atrophic carcinoma, ductal carcinoma, and mucinous fibroplasia. GS 5 + 3 = 8 (GG4) cancer is very rare with contemporary grading. The reliability of conclusions from retrospective databases regarding the clinical significance of this grade combination without slide re-review is questionable.
Prostatic Ductal Adenocarcinoma Controlled for Cancer Grade and Tumor Volume Does Not Have an Independent Effect on Adverse Radical Prostatectomy Outcomes Compared to Usual Acinar Prostatic Adenocarcinoma
2020, Urology
To study if prostatic ductal adenocarcinoma (PDA) controlled by Grade Group (GG), PSA, and tumor volume (TV) is an independent predictor of adverse radical prostatectomy (RP) outcomes.
One-hundred and twenty-eight PDA and 1141 acinar continuous RPs were studied. Each tumor nodule (TN) was individually graded, staged, and its TV measured. Univariate analysis (UVA) identified features associated with lymph node metastasis (LN+), extraprostatic extension (EPE), positive surgical margins (SM+), and seminal vesicle invasion (SV+). We then assessed PDA effect on RP outcomes in a multivariate analysis (MVA).
In 127 cases PDA was present in 1 TN and no TN was pure PDA. One-hundred and twenty-three cases had PDA in TNs with highest grade, stage, and TV. Patients with PDA were older (65 vs 63 years, P < 0.001), had higher GG (P < 0.001), and LN+ (6.3% vs 2.7%, P = 0.049). Controlling these variables by GG eliminated statistical significance. Overall, there were 3249 separate TNs (129 PDA and 3120 acinar). In UVA, PDA predicted EPE (92/124 vs 517/3045), SV+ (28/1129 vs 116/3,120), and SM+ (51/129 vs 296/3120), all P < 0.001. In MVA, PDA lost its effect on EPE (OR = 0.88, P = 0.64), SM+ (OR = 0.86, P = 0.5), and SV+ (OR = 0.99, P = 0.98).
Controlled for grade and TV, PDA was not an independent predictor of adverse RP outcomes, but former 2 were. Hence, higher GG and TV associated with PDA TNs may be predictive of adverse RP outcomes rather than PDA by itself. These conclusions may be used in preoperative risk stratification and definitive therapy planning when PDA is identified on needle biopsy.
Comparison of PSA-density of the transition zone and whole gland for risk stratification of men with suspected prostate cancer: A retrospective MRI-cohort study
2019, European Journal of Radiology
To compare the correlation of transition zone prostate-specific antigen density (TZPSAD) versus whole gland (WG) density (PSAD) with Gleason score.
In this single-center, retrospective cohort study, men undergoing MRI of the prostate in 2015 and 2016 who had a transperineal template saturation biopsy within 6 months of MRI were included (n = 178; median age 64 y, interquartile range [IQR] 58–68 y; PSA 6.6 ng/ml, 4.6–9.7 ng/ml). The WG and TZ were segmented voxel-wise on T2-weighted transverse planes. The volumes and corresponding PSA-densities were calculated. Correlations with the Gleason score were assessed with Spearman’s rho. Optimal thresholds of the PSA densities were computed using the Youden Index of the receiver-operating-characteristics curve. A p-value of ≤ 0.05 was considered statistically significant.
Median WG volume was 45 ml (IQR: 33.9–58.7 ml, range: 17.2–165.3 ml), median volume of the TZ was 27.3 ml (IQR: 19.2–39.3 ml, range: 9.0–141.1 ml). Both PSA density values, PSAD and TZPSAD, correlated significantly with the Gleason score: The PSAD (rho = 0.39) showed significantly weaker correlation than the TZPSAD (rho = 0.44, p = 0.05). ROC analysis revealed an ideal cut-off of 0.15 ng/ml² for PSAD (95%-CI: 0.09–0.16 ng/ml²) and 0.22 ng/ml² for the TZPSAD (0.15-0.32 ng/ml²) for discrimination between Gleason 3 + 4 and 4 + 3.
The TZPSAD exhibited a stronger correlation with cancer dedifferentiation than PSAD and may thus be a better surrogate marker for cancer aggressiveness than PSAD. Moreover, the TZPSAD threshold of 0.22 ng/ml² may help in risk stratification of men with suspected PCa.

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: Financial Disclosure: The authors declare that they have no relevant financial interests.

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OncologyBiopsy Criteria for Determining Appropriateness for Active Surveillance in the Modern Era

Objective

Methods

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

Conclusions

Urology

Urology

J Urol

J Urol

J Urol

J Urol

Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer

JAMA

Pathological outcomes in men with low risk and very low risk prostate cancer: implications on the practice of active surveillance

J Urol

Active surveillance program for prostate cancer: an update of the Johns Hopkins experience

J Clin Oncol

The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma

Am J Surg Pathol

Should intervening benign tissue be included in the measurement of discontinuous foci of cancer on prostate needle biopsy? Correlation with radical prostatectomy findings

Am J Surg Pathol

Initial high-grade prostatic intraepithelial neoplasia with carcinoma on subsequent prostate needle biopsy: findings at radical prostatectomy

Am J Surg Pathol

Prostate cancer and the Will Rogers phenomenon

J Natl Cancer Inst

Do adenocarcinomas of the prostate with Gleason score (GS) </=6 have the potential to metastasize to lymph nodes?

Am J Surg Pathol

Oncology
Biopsy Criteria for Determining Appropriateness for Active Surveillance in the Modern Era