Extent of extracapsular extension in localized prostate cancer

doi:10.1016/S0090-4295(99)00458-6

Urology

Volume 55, Issue 3, March 2000, Pages 382-386

This study was presented at ASTRO 98, Phoenix, Arizona, October 1998.

https://doi.org/10.1016/S0090-4295(99)00458-6 Get rights and content

Abstract

Objectives. To measure the radial extent of extracapsular penetration by tumor cells, thereby providing estimates of the margins needed around target volumes. New radiotherapeutic techniques, like brachytherapy and conformal radiotherapy, irradiate small volumes and reduce the dose to periprostatic tissues. Even in the early stages of localized prostate cancer, extracapsular extension (ECE) is commonly seen.

Methods. Two hundred sixty-five consecutive radical prostatectomy specimens were analyzed for the presence of ECE. ECE was found in 92 of all cases (35%); measurements were performed in 79 of the 92 cases. A total of 98 ECE sites were evaluated in the 79 cases. The distance of tumor outside the capsule was measured in millimeters. Extension less than 0.1 mm was considered as “focal.”

Results. The site of ECE was posterolateral in 53% of cases, lateral in 24%, posterior in 13%, and at the base in 10%. The median amount of ECE at all sites was 1.1 mm (mean 1.7). However, the range was wide; the minimum measurable extent was 0.1 mm and the maximum 10.0 mm. The extent was within 3.8 mm for 90% of all cases. By stratifying cases with favorable and unfavorable tumors, the 90th percentiles of ECE were as follows: 3.3 mm for favorable tumors (clinical Stage T1-2, initial prostate-specific antigen 10 ng/mL or less, and biopsy Gleason score 6 or less) and 3.9 mm for unfavorable tumors (clinical Stage T3, initial prostate-specific antigen greater than 10 ng/mL, or biopsy Gleason score 7 or greater).

Conclusions. Most of the ECE was at posterolateral sites. The extent of disease outside the prostate was within 4 mm in 90% of cases. Since ECE was observed in 30% to 60% of all patients with clinical Stage T1-2 prostate cancer, only 3% to 7% of all such cases would have disease extent exceeding 4 mm. The present study provides useful estimates of the amount of ECE. These estimates could be potentially used in planning the target volumes for treatment of prostate cancer with either conformal radiotherapy or brachytherapy.

Section snippets

Material and methods

Two hundred sixty-five radical prostatectomy specimens were reviewed by the same pathologist for the presence of ECE. Prostate glands from the radical prostatectomy specimens were received fresh in the surgical pathology laboratory. The glands were weighed, measured, inked, and fixed in formalin for at least 24 hours. We did not check whether fixation would affect the measurement owing to shrinkage of the gland. There is no reliable way of internally checking the geometry of the gland before

Patient characteristics

Most patients had early-stage disease (Table I). Five patients with T3 disease made up 6% of the cases. The median pretreatment prostate-specific antigen (iPSA) level was 7.4 ng/mL, with two thirds of the patients having an iPSA of 10 ng/mL or more. More than one half of the patients had a biopsy Gleason score (bGS) of 6 or less.

Cases and sites of ECE

Of the 265 patients, 92 (35%) had ECE. Measurements were performed in 79 of the 92 cases. A total of 98 sites of ECE were found in the 79 patients. More than one half

Comment

With the advent of current radiation techniques such radioactive seed implants and conformal radiotherapy, the volume of tissues irradiated has decreased significantly. The margins needed around prostate tissue necessary to encompass cancer extension have not been clearly defined. Since the prostate gland rather than a tumor mass is visualized, the definitions of gross target volume and clinical target volume are somewhat inadequate. Prostate cancer arises preferentially in certain areas within

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Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens
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Assessing the impact of brachytherapy boost and androgen deprivation therapy on survival outcomes for patients with unfavorable intermediate-risk prostate cancer patients treated with external beam radiotherapy
2022, Brachytherapy
Current recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa.
The National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios.
Median follow-up was 60 months (range: 3–168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87–0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69–0.85], p = 3 × 10⁻⁷) and EBRT+BT+ADT (HR: 0.75 [0.67–0.83], p = 6 × 10⁻⁸) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87–1.11], p = 0.82).
In a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.
MRI-defined treatment margins, urinary toxicity, and PSA response in LDR prostate brachytherapy
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Implant quality metrics as measured by D90 and V100 do not address the adequacy of periprostatic margins. Relative margin deficiencies may relate to efficacy and margin excesses to post-implant toxicity. Our purpose is to determine MRI-defined treatment margins on prostate achieved with LDR brachytherapy.
Post implant CT and MR images from 487 consecutive patients who received LDR brachytherapy from 2010 to 14 were co-registered. Four prostate quadrants were defined; anterior-superior (AS), posterior-superior (PS), anterior-inferior (AI), posterior-inferior (PI). Dosimetric variables were measured for prostate, and for each quadrant with a 0-, 2-, 3-, and 5-mm margin, as well as for the membranous urethra defined on MRI.
Prostate D90 (no margin) was associated with D90 to the volume enclosed by 2 mm, 3 mm and 5 mm margins (R2 = 0.9 – 1.0) with an average 7.1% decrease in dose per mm of margin. Mean D90 for PS, AI and PI quadrants were > 110% of prescription dose for margins of 2-, 3-, and 5-mm. AS quadrant mean D90s were generally lower (83.2% for 2 mm, 76.4% for 3 mm and 62.2% for 5 mm). Urethral strictures (n = 9) were associated with higher doses in the AI quadrant, and higher membranous urethral V125 (51 vs. 32%, p 0.013) and V150 (34.5 vs. 17.6%, p 0.01).
Using MR-CT post implant dosimetry, margin coverage up to 5 mm was excellent with less margin coverage in the AS quadrant. Late ≥ grade 2 toxicity and urinary strictures are more likely to occur with relative margin excess in the anterior-inferior quadrant and higher doses caudal to the prostate apex. Within this analysis, there was no relationship between treatment margins, and PSA outcome.
Optimizing Surgical Techniques in Robot-Assisted Radical Prostatectomy
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Lack of Benefit From the Addition of External Beam Radiation Therapy to Brachytherapy for Intermediate- and High-risk Prostate Cancer
2017, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
The seminal vesicles or surrounding organs likely have difficulty receiving a sufficient dosage from conventional brachytherapy (17). However, because the radial extent of extraprostatic disease for cT1-T2 tumors is almost always ≤5 mm (18, 19), extraprostatic extension should generally be well covered. Given the increasing availability of endorectal coil magnetic resonance imaging and its ability to detect extensive extraprostatic extension and seminal vesicle invasion, patients appropriate for brachytherapy monotherapy can be more readily identified than was the case in the past (20-22).
A recent randomized controlled trial demonstrated that the addition of external beam radiation therapy (EBRT) to brachytherapy did not improve progression-free survival in select patients with intermediate-risk prostate cancer. We evaluated whether the addition of EBRT to brachytherapy improves prostate cancer–specific mortality (PCSM) for intermediate- and high-risk disease using a large national database.
We identified 5836 patients in the Surveillance, Epidemiology, and End Results–Medicare linked database with a diagnosis of National Comprehensive Cancer Network intermediate-risk (Gleason score 7, prostate-specific antigen 10-20 ng/mL, or stage cT2b-T2c) or high-risk (Gleason score 8-10 or prostate-specific antigen >20 ng/mL and stage ≤cT3a) prostate cancer who had undergone brachytherapy, with or without EBRT and androgen deprivation therapy (ADT). Patients were diagnosed from 2004 through 2009. Intermediate-risk patients with Gleason score ≤3+4 and 1 intermediate-risk factor were considered favorable and all others unfavorable. We used multivariable Fine-Gray competing risks regression to study PCSM while adjusting for sociodemographic and clinical factors and ADT use.
Overall, 50.3% of intermediate- and high-risk patients who received brachytherapy and EBRT did not have significantly improved PCSM compared with that of the patients who received brachytherapy alone (adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 0.69-3.11; P=.322; 5-year PCSM 2.4% vs 1.0%). This lack of benefit was seen among favorable intermediate-risk (AHR 2.66, 95% CI 0.93-7.62, P=.069; 5-year PCSM 1.3% vs 0.6%), unfavorable intermediate-risk (AHR 0.68, 95% CI 0.16-2.96, P=.612; 5-year PCSM 1.0% vs 1.2%), and high-risk (AHR 1.82, 95% CI 0.67-4.98, P=.242; 5-year PCSM 5.3% vs 2.1%) subgroups.
These results suggest that certain patients with intermediate- or high-risk prostate cancer treated with brachytherapy might not benefit from the addition of EBRT. A randomized controlled trial of brachytherapy plus ADT with or without EBRT for unfavorable intermediate- and favorable high-risk organ-confined prostate cancer should be undertaken.
A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer
2017, International Journal of Radiation Oncology Biology Physics
We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP).
From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer–specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM.
The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001).
HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR.
ACR appropriateness criteria: Permanent source brachytherapy for prostate cancer
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To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy.
The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography–based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity.
Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians.

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Adult UrologyExtent of extracapsular extension in localized prostate cancer

Abstract

Section snippets

Material and methods

Patient characteristics

Cases and sites of ECE

Comment

Stage T1-2 prostate cancera multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy

Int J Radiat Oncol Biol Phys

Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens

J Urol

Adult Urology
Extent of extracapsular extension in localized prostate cancer