Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols.
ABSTRACT Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs.
To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy.
The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤ 6 on transrectal biopsy with ≥ 10 cores.
Radical prostatectomy without neoadjuvant treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤ 6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared.
A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols.
Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer.
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ABSTRACT: Background: Many low risk prostate cancer (PC) patients diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade cancer (Gleason≥7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools available preoperatively are needed to improve our ability to recognize upgrading in low risk patients. Methods: Over 30 clinicopathologic parameters were assessed in consecutive Gleason 6 biopsy patients who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason≥7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in two separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using ROC curves, calibration, and decision analysis. Results: On multivariable analysis variables predicting upgrading were PSA density using ultrasound (OR=229, p=0.003), obesity (OR=1.90, p=0.05), number of positive cores (OR=1.23, p=0.01), and maximum core involvement (OR=0.02, p=0.01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all three cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated AUCs of 0.597-0.672 for predicting upgrading in subsets of very low risk men who meet AS criteria(all p<0.001) allowing further risk stratification of these individuals. Conclusion: We have developed and externally validated a nomogram that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform lower risk PC patients considering treatment or AS.Cancer 05/2013; · 5.20 Impact Factor
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ABSTRACT: OBJECTIVE. The purpose of this study was to compare findings at nongaussian diffusional kurtosis imaging and conventional diffusion-weighted MRI as markers of adverse pathologic outcomes among prostate cancer patients who are active surveillance candidates and choose to undergo prostatectomy. MATERIALS AND METHODS. Fifty-eight active surveillance candidates (prostate-specific antigen concentration, < 10 ng/mL; clinical tumor category less than T2a; Gleason score, 3 + 3; ≤ 25% of biopsy cores positive for tumor; ≤ 50% tumor involvement of any individual core; ≤ 20% tumor involvement across all cores) who underwent prostatectomy and preoperative 3-T MRI including diffusional kurtosis imaging (b values, 0, 500, 1000, 1500, and 2000 s/mm(2)) were included. Adverse pathologic features at prostatectomy were defined using two schemes of varying stringency. One scheme (less stringent) was presence of a Gleason score greater than 6 or extracapsular extension (n = 19). The other scheme (more stringent) was presence of a Gleason score greater than 6, extracapsular extension, or an index tumor 10 mm or larger (n = 35). Parametric maps displaying standard apparent diffusion coefficient (ADC), kurtosis (K) representing nongaussian diffusion behavior, and diffusion (D) representing a diffusion coefficient adjusted for nongaussian (kurtosis) behavior were reviewed, and the most abnormal region was recorded for each metric. Associations between these metrics and the presence of adverse final pathologic findings were assessed with unpaired Student t tests and receiver operating characteristic analyses. RESULTS. For both schemes, only D was significantly lower in patients with adverse final pathologic findings (p = 0.006, p = 0.025). K tended to be greater in patients with adverse final pathologic findings for the more stringent scheme (p = 0.072). ADC was not significantly different in the presence of adverse final pathologic findings for either scheme (p = 0.357, p = 0.383). With either scheme, D had a larger area under the receiver operating characteristics curve (AUC) for predicting adverse final pathologic results (AUC, 0.691 and 0.743) than did ADC (AUC, 0.569 and 0.655) or K (AUC, 0.617 and 0.714), but the difference was not significant (p = 0.183, p = 0.734). CONCLUSION. Preliminary results suggest that diffusional kurtosis imaging findings may have more value than findings at conventional diffusion-weighted MRI as a marker of adverse final pathologic outcome among active surveillance candidates.American Journal of Roentgenology 10/2013; 201(4):840-6. · 2.90 Impact Factor
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ABSTRACT: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 1.72 per 0.1 unit increase PSAD, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 1.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals. A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance. Cancer 2013. © 2013 American Cancer Society.Cancer 09/2013; · 5.20 Impact Factor