Extent Of Extraprostatic Extension Research Articles

Multifocal Extraprostatic Extension of Prostate Cancer.

To investigate the prognostic utility of multifocal extraprostatic extension (EPE) on biochemical recurrence after radical prostatectomy. We conducted retrospective analysis of biochemical recurrence and prognostic pathologic variables in 673 men with stage pT3a/pT3b prostate cancer from 2000 to 2012. Extent of EPE on radical prostatectomy was divided into three groups: focal EPE (tumor dimension <0.8 mm), established (≥ 0.8 mm), and multifocal (more than one focus of EPE <0.8 mm). Type of EPE had significant effect on recurrence with progressively lower progression-free probability and higher recurrence probability from focal to established to multifocal. Multifocal and established tumors exhibited worse prognostic features and higher hazard ratio than focal. In multivariate analysis, established and multifocal were independent prognostic factors with the greatest adverse prognostic significance associated with multifocal. Identification of multifocal EPE provides important prognostic information associated with increased likelihood of recurrence compared to focal and established tumors.

221P - Prognostic impact of pT3a subclassification based on extent of extraprostatic extension after robot-assisted radical prostatectomy

221P - Prognostic impact of pT3a subclassification based on extent of extraprostatic extension after robot-assisted radical prostatectomy

Impact of the extent of extraprostatic extension defined by Epstein's method in patients with negative surgical margins and negative lymph node invasion.

To assess the impact of the degree of extraprostatic extension (EPE) on biochemical recurrence (BCR) and utility of the original Epstein's criteria to define EPE in a cohort of pT3aN0 without positive surgical margin (PSM). A two-center retrospective analysis was performed on data from 490 pT3aN0 patients who underwent radical prostatectomy between 2000 and 2012. Patients with neoadjuvant and/or adjuvant therapy, detectable PSA and PSM were excluded. Our pathologists used Epstein's criteria to report the degree of EPE. When pathology reports did not reflect the terms 'focal' or 'established' (non-focal), slides were analyzed by a single genitourinary pathologist for final evaluation. The end point was defined by BCR. Selection criteria yielded 247 patients. Mean follow-up was 56.3±4.6 months; mean age at surgery was 62.5 years. Sixty-one (24.7%) patients experienced BCR during follow-up. Patients with focal extension had a 5-year recurrence-free survival of 89% versus 80% for those with non-focal extension (P=0.0018). In multivariate analysis, both pathologic Gleason score (hazard ratio 2.5; 95% confidence interval 1.4-4.5; P=0.002) and the extent of EPE (hazard ratio 1.8; 95% confidence interval 1.1-3.5; P=0.029) were significant predictors of BCR. The extent of EPE is an independent predictor of BCR in pT3aN0 prostate cancer without PSM. This study reinforces the utility of the subjective Epstein approach already adopted by most pathologists for quantification of the extent of EPE.

Extraprostatic extension (EPE) of prostatic carcinoma: is its proximity to the surgical margin or Gleason score important?

To examine the association between histopathological factors of extraprostatic prostate cancer and outcome. Patients with extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph node involvement were analysed from a consecutive radical prostatectomy cohort of 1136 (2002-2006) for: (i) distance of EPE from the margin; (ii) Gleason score of the EPE; and (iii) extent of EPE. Log-rank, Kaplan-Meier, and Cox regression analyses were performed. The study included 194 pT3a, pN0, R0 patients with a median follow-up of 5.4 years, with 37 (19%) patients experiencing biochemical relapse (BCR). On univariable analysis, patients with a Gleason score of ≥8 in the extraprostatic portion showed increased incidence of BCR compared with those with Gleason scores of ≤7 (P = 0.03). The proximity of the EPE to the margin (0.01-7.5 mm) did not correlate with BCR. On multivariable analysis, the extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did not correlate with BCR. Data from this study using current International Society of Urological Pathology Gleason scoring and EPE criteria indicate that close proximity of EPE to the margin is not associated with recurrence. Gleason score ≥8 within EPE is associated with an increased BCR risk on univariable analysis, but larger studies are required to confirm whether extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise overall Gleason score 7 cancer.

Extent of extraprostatic extension independently influences biochemical recurrence-free survival: evidence for further pT3 subclassification.

To evaluate the impact of the extent of extraprostatic extension (EPE) on biochemical recurrence-free survival (BCRFS) after radical prostatectomy (RP). We queried our RP database from 2004 to 2013. Extent of EPE on RP was divided into 3 groups: no EPE, focal EPE (F-EPE; a few extraprostatic cancer glands on 1-2 slides), and nonfocal EPE (NF-EPE). Multivariate Cox proportional hazard models determined the influence of EPE on BCRFS. A total of 10,750 men underwent RP during the study period. Of these, 7843 men (73.0%) had no EPE, 1258 (11.7%) men had F-EPE, and 1649 men had (15.3%) NF-EPE. Overall BCRFS was worse in men with NF-EPE than those with F-EPE or no EPE. In a multivariate model, F-EPE and NF-EPE were both independently associated with worse BCRFS compared with no EPE (F-EPE: hazard ratio, 2.41; 95% confidence interval, 1.84-3.10; P <.0001; NF-EPE: hazard ratio, 3.57; 95% confidence interval, 2.89-4.40; P <.0001). When stratified by Gleason score in men without seminal vesicle invasion or lymph node metastases, there was no difference in BCRFS for Gleason score <6, 3 + 4 = 7, 4 + 3 = 7, and 8 for F-EPE vs no EPE; however, patients with Gleason score of 9-10 with F-EPE had worse BCRFS. Patients with NF-EPE had significantly worse BCRFS for Gleason score <6, 7, and 8 and a trend for worse BCRFS for Gleason score 9-10 compared with no EPE. Although all men with EPE have higher BCRFS after RP, men with NF-EPE have worse BCRFS than those with F-EPE, supporting the need to substratify pT3a prostate cancer in the American Joint Committee on Cancer staging system.

MP42-10 GLEASON SCORE 6 PROSTATE CANCER AND PRESENCE OF PATHOLOGICAL STAGE T3 DISEASE

MP42-10 GLEASON SCORE 6 PROSTATE CANCER AND PRESENCE OF PATHOLOGICAL STAGE T3 DISEASE

Endorectal magnetic resonance imaging for predicting pathologic T3 disease in Gleason score 7 prostate cancer: Implications for prostate brachytherapy

To determine the ability of endorectal magnetic resonance imaging (erMRI) and other pretreatment factors to predict the presence and extent of extraprostatic extension (EPE) in men with Gleason score (GS) 7 prostate cancer. We included patients with clinical stage T1c-T2c, GS=7 (3+4 or 4+3), and prostate-specific antigen (PSA) <10ng/mL who underwent pre-prostatectomy erMRI. We compared pathologic EPE findings with pretreatment factors. One hundred seventy-one men were eligible for inclusion. Pretreatment characteristics were: median age=60 years (42-76); median PSA 4.9ng/mL (0.4-9.9); GS 3+4=61%; T1c=51%; T2a=25%; T2b=21%; T2c=3%; ≥50% positive cores=46%; EPE-positive (EPE+) erMRI=28%. Thirty-three percent had pathologic EPE. Increasing T-stage (p<0.0001) and EPE+ erMRI (p<0.0001) were significant predictors of pathologic EPE, whereas GS (4+3 vs. 3+4) (p=0.14), percentage of positive core biopsies (p=0.15), and pretreatment PSA (p=0.41) were not. Median EPE distance was 1.75mm (range, <1-15mm). The rates of EPE >5mm and EPE >3mm were 11% and 15%, respectively. The odds ratios for erMRI detection of any EPE and of EPE >5mm were 3.06 and 3.75, respectively. T-stage and EPE+ erMRI predict pathologic EPE in men with GS 7 prostate cancer. The ability of erMRI to detect EPE increases with increasing EPE distance. These findings may be useful in patient selection for prostate brachytherapy monotherapy.

Definition and Dosimetric Evaluation of a Clinical Target Volume (CTV) in the Post Implant (CT/MR Fusion) Analysis of Low-Dose-Rate Brachytherapy for Prostate Cancer at Princess Margaret Hospital

Purpose: The extent of extra prostatic extension in low and intermediate risk prostate cancer is mostly confined within a radial distance of 3mm which have implications in evaluating the post-implant dosimetry of LDR brachytherapy. There is a scarcity of data in evaluating the dosimetry around the prostate in the post implant setting. In this study, we defined a CTV and evaluated its dosimetry in the post implant CT/MR scans done at 1 month after the LDR brachytherapy procedure. Materials and Methods: The initial consecutive 71 patients who underwent LDR brachytherapy under a single physician at Princess Margaret Hospital from June 2009 to July 2010 were included in this retrospective study. The margins used in the preplan ultrasound were 3mm anterolaterally 5mm inferiorly and 0mm posteriorly. On the post implant MRI, the CTV was created by adding 3mm uniform margins around the prostate as per guidelines of ESTRO and AAPM. We modified this CTV by editing it back from the bladder wall and rectal wall to respect the anatomic barriers of microscopic spread. We evaluated the dosimetry of prostate and CTV using the dosimetric parameters V80, V90, V100, V150, V200, D80, D90 and D100 after performing the CT/MR fusion. Implants were qualified as optimal if their V100 was >85% and D90 was >90% for the prostate in this analysis and the same indicators were applied for the CTV. Univariate analysis using Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical variables was performed to evaluate associations of factors with V100 and D90 for the CTV. Results: The mean (SD) prostate V100 and D90 were 95.5% (4.2) and 117% (10) respectively with only 1 patient having sub optimal implant (V100 <85% and D90 <90%). The mean (SD) V100 and D90 for the CTV were also acceptable at 90.6% (4.9) and 103% (9), respectively. The detailed analysis is given in the table.Tabled 1VariableProstate Mean (SD)CTVMean (SD)V80 (%)99 (1.5)97 (2.5)V90 (%)98 (2.9)94 (2.5)V100 (%)95.5 (4)90.6 (4.9)V150 (%)62 (11)57 (9.3)V200 (%)31 (8)28 (7)D80 (%)131 (11)121 (10)D90 (%)117 (10)103 (9.2)D100 (%)65 (10)55 (8) Open table in a new tab Six patients had V100 <85% and 7 patients had D90 <90% for the CTV. On univariate analysis, the factors which correlated with suboptimal implant for the CTV were edema and seed implantation technique. The mean (SD) edema for patients with V100 <85% was 18% (10) and with D90 <90% was 15% (12). The corresponding values for the optimal implants both in terms of V100 and D90 were 3% (13). Patients implanted with exclusively loose seeds (15 patients only) had higher incidence of implants with V100 <100% and D90 <90% (26%) compared to patients who had strands on the antero-lateral margins (56 patients; 3.5%). The prostate volume (ranging from 18 to 73cc) did not influence the dose coverage of CTV in our study. Conclusions: In this study, we defined the CTV as a 3mm expansion of the prostate to account for extra capsular extension in the post-implant setting for LDR brachytherapy and evaluated its dosimetry. We were able to achieve adequate dose coverage of CTV in most patients with current technique but implants with optimal dosimetry to prostate still may have suboptimal D90 and V100 for the CTV especially in the presence of post-implant edema. A consensus is needed for definition and evaluation of CTV in post-implant setting for LDR prostate brachytherapy.

Radial Distance of Extraprostatic Extension Measured by an Ocular Micrometer is an Independent Predictor of Prostate-specific Antigen Recurrence: A New Proposal for the Substaging of pT3a Prostate Cancer

Extraprostatic extension is an unfavorable prognostic factor for prostate cancer. Consequently, it has been assigned to pT3a in the current 2002 tumor, lymph node, metastasis staging system. The aim of our study is to analyze the extent of extraprostatic extension by 8 quantitative methods and to determine which is best for substaging of pT3a tumors. We studied 83 patients with extraprostatic extension after radical prostatectomy for clinically localized prostatic adenocarcinoma. The extent of extraprostatic extension was evaluated using 8 quantitative methods. Univariate and multivariate analyses were performed to determine which measurement best predicts prostate-specific antigen (PSA) recurrence. In the univariate analysis, the radial distance of extraprostatic tumor measured by ocular micrometer was associated with PSA recurrence (P = 0.02). No significant association was observed between PSA recurrence and other measurements of extraprostatic extension, including focal versus established extraprostatic extension using Epstein's criterion, focal versus established extraprostatic extension using Wheeler's modified criterion, the number of extraprostatic neoplastic glands, unilateral versus bilateral involvement, circumferential length of extraprostatic tumor, unifocal versus multifocal involvement, and volume of extraprostatic tumor. In the multivariate analysis, radial distance remained an independent predictor of PSA recurrence (hazard ratio, 2.4; 95% confidence interval, 1.12-5.01; P=0.02). The radial distance of the extraprostatic extension measured by ocular micrometer is an independent prognostic factor for pT3 prostate cancer. Two-year and 4-year PSA recurrence-free survival was 62% and 35%, respectively, for those patients with radial distance or =0.75 mm. We recommend reporting this parameter routinely for radical prostatectomy specimens. The strength of its prognostic value for PSA recurrence makes it a potential criterion for incorporation into a future tumor, lymph node, metastasis staging system.

PROGNOSTIC FACTORS FOR SURVIVAL OF PATIENTS WITH PATHOLOGICAL GLEASON SCORE 7 PROSTATE CANCER: DIFFERENCES IN OUTCOME BETWEEN PRIMARY GLEASON GRADES 3 AND 4

We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.

Adenocarcinoma of the prostate invading the seminal vesicle: prognostic stratification based on pathologic parameters

Objectives. To stratify the prognosis of lymph node-negative, seminal vesicle-positive tumors in men with prostate cancer after radical retropubic prostatectomy. Methods. Sixty cases were analyzed for multiple parameters and correlated with postoperative biochemical (prostate-specific antigen) progression. Variables included Gleason score, primary Gleason pattern, percentage of Gleason pattern 4, any presence of Gleason pattern 5, method of seminal vesicle invasion (SVI), margin positivity, SVI extent, SVI bilaterality, vascular invasion, extent of extraprostatic extension, length of tumor extending along the seminal vesicles, presence of intraductal carcinoma within the prostate, bladder neck margin positivity, and tumor volume. Results. We were able to stratify the prognosis based on the combination of a variation of the Gleason score and margin status and vascular invasion status. Using this stratification, a few patients had an excellent long-term prognosis, with most patients split into two groups, one experiencing rapid and the other slower progression. Conclusions. SVI is not associated with a uniformly poor prognosis. Rather, tumors can be substratified by pathologic parameters into groups with differing prognoses based on routine histologic examination.