Influence of Pretreatment and Treatment Factors on Intermediate to Long-Term Outcome After Prostate Brachytherapy
ABSTRACT We describe how treatment factors influence biochemical freedom from failure, local control, freedom from metastasis and cause specific survival in patients treated with prostate brachytherapy.
We followed 2,111 men who underwent brachytherapy a median of 6 years (range 2 to 17). Median prostate specific antigen was 7 ng/ml. Of the men 1,455 (68.9%) had clinical stage T2a or less and 1,428 (67.6%) had Gleason score less than 7. A total of 1,171 patients (55.5%) received (125)I, 221 (10.4%) received (103)Pd and 719 (34.1%) received supplemental external beam irradiation combined with (103)Pd. Post-implant dosimetry was done 30 days after implantation with doses converted to the biologically effective dose. Prostate biopsy was done 2 years after permanent prostate brachytherapy in 586 men (27.8%). Survival functions were determined by the Kaplan-Meier method and Cox regression with proportions tested by the log rank test.
The 12-year biochemical freedom from failure rate was 78.6%, and stage, Gleason score, prostate specific antigen and biologically effective dose were significant predictors (p = 0.007, <0.001, 0.005 and <0.001, respectively). In 964 patients at low risk the biochemical freedom from failure rate was 88.1% and significant predictors were hormonal therapy (p = 0.030), prostate specific antigen (p = 0.026) and biologically effective dose (p = 0.003). In 499 patients at intermediate risk the biochemical freedom from failure rate was 79.2% with biologically effective dose a significant predictor (p <0.001). In 648 men at high risk the biochemical freedom from failure rate was 67% and significant predictors were hormonal therapy, Gleason score and biologically effective dose (p = 0.036, <0.001 and 0.012, respectively). The local failure rate was 7.3% with biologically effective dose a significant predictor (p <0.001). Prostate biopsy was positive in 21 of 121 cases (21.5%) for a biologically effective dose of 150 Gy2 or less, in 14 of 248 (5.6%) for greater than 150 to 200 Gy2 and in 3 of 193 (1.6%) for greater than 200 Gy2 (p <0.001). The 12-year freedom from metastasis rate was 95.2% with Gleason score a significant predictor (p <0.001). Cause specific survival at 12 years was 94.5% with Gleason score and biologically effective dose significant predictors (p <0.001 and 0.027, respectively).
Permanent prostate brachytherapy yields excellent long-term oncologic outcomes. High biologically effective dose may need to be delivered to achieve successful biochemical freedom from failure, local control and cause specific survival.
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- "The latter is recommended by some experts only in a subset of patients depending on clinical stage, serum PSA, biopsy GS, extent of cancer on biopsy, and the presence or absence of perineural invasion . When brachytherapy is used to treat high-risk category patients, high doses are usually used, and a combination with hormonal therapy and EBRT is typically given . "
ABSTRACT: CONTEXT: The Gleason grading system is one of the most powerful predictors of outcome in prostate cancer and a cornerstone in counseling and treating patients. Since its inception, it has undergone several modifications triggered by a change in clinical practice and a better understanding of the cancer's histologic spectrum and variants and their prognostic significance. OBJECTIVE: To provide an overview of the implementation and the impact of the Gleason system as a predictive and prognostic tool in all available treatment modalities, and to compare the original and modified Gleason systems in major pathologic and clinical outcome data sets. EVIDENCE ACQUISITION: A comprehensive nonsystematic Medline search was performed using multiple Medical Subject Headings such as Gleason, modified, system, outcome, biopsy, prostatectomy, recurrence, prognosis, radiotherapy, and focal therapy, with restriction to the English language and a preference for publications within the last 10 yr. All Gleason grade-related studies in the last 3 yr were reviewed. For studies before this date, we relied on prior culling of the literature for various recent books, chapters, and original articles on this topic. EVIDENCE SYNTHESIS: Using the modified grading system resulted in disease upgrading with more cancers assigned a Gleason score ≥7 than in the past. It also resulted in a more homogeneous Gleason score 6, which has an excellent prognosis when the disease is organ confined. The vast majority of studies using both systems showed that Gleason grading of adenocarcinomas on needle biopsies and radical prostatectomies was strongly associated with pathologic stage, status of surgical margins, metastatic disease, biochemical recurrence, and cancer-specific survival, with the modified system outperforming the original one in some large series. A description of the continuous incorporation of this parameter in the clinical decision making for treating prostate cancer using all currently used treatment modalities is presented, and the findings of studies before and after the inception of the modified grading system, if available, are compared. The proposed contemporary grading prognostic categories are 3+3, 3+4, 4+3, 8, and 9-10. CONCLUSIONS: The Gleason score is one of the most critical predictive factors of prostate cancer regardless of the therapy used. Modernization of the Gleason grading system has resulted in a more accurate grading system for radical prostatectomy (RP) but has complicated the comparison of data before and after the updating. A better prognostication with the updated Gleason grading system for patients treated with modalities other than surgery can only be postulated at this time because there are limited conflicting data on radiation and no studies on other treatment modalities. Its greatest impact is the uniformly excellent prognosis associated with Gleason score 6 in RPs.European Urology 10/2012; 63(5). DOI:10.1016/j.eururo.2012.10.015 · 12.48 Impact Factor
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ABSTRACT: Low dose rate permanent prostate brachytherapy is an excellent choice for men with localized prostate cancer. We review the contemporary understanding of genitourinary toxicity after prostate brachytherapy with particular attention directed toward urinary retention and incontinence. Urinary retention, though typically transient, has been reported in 1.5-34 % of patients, and significantly impacts health-related quality of life. Pre-treatment predictors include prostate size and high pre-treatment urinary symptom score. Validated nomograms have recently been developed to prospectively identify those at risk for urinary retention. In patients with refractory bladder outlet obstruction, a minimal transurethral resection of the prostate (TURP) is employed following a time interval sufficient for delivery of the full prescribed radiation dose. Urinary incontinence is uncommon following brachytherapy but is strongly associated with prior or subsequent TURP, where published incidence reports range from 0-19 %. Ongoing research seeks to identify genetic polymorphisms that may select individuals at greater risk of developing radiation related toxicities.Current Bladder Dysfunction Reports 09/2013; DOI:10.1007/s11884-013-0188-5
Conference Paper: Dynamic selection of dispatching rules by fuzzy inference[Show abstract] [Hide abstract]
ABSTRACT: Proposes a fuzzy inference-based selection of dispatching rules, adapting the scheduling decision to the dynamic changes in the manufacturing environment. In the proposed method, the performance of different dispatching rules is studied while varying production conditions. Environmental variables are then used to detect those changes, as input to the fuzzy inference system. The fuzzy inference will thereupon attribute preference levels to the dispatching rules, according to their adequacy to the current environment. The scheduling is made using partitioned combination of dispatching rules. In order to verify the validity of the proposed method, an application to FMS scheduling is presentedFuzzy Systems Proceedings, 1998. IEEE World Congress on Computational Intelligence., The 1998 IEEE International Conference on; 06/1998