Aktif izlem ile takip edilen lokalize prostat kanserli hastalarda 5 alfa redüktaz inhibitörlerinin prognoza etkisi
Impact of the 5-alpha reductase inhibitors on patients with localized prostate cancer followed with active surveillance
- Tez No: 293478
- Danışmanlar: PROF. DR. ÖZDAL DİLLİOĞLUGİL
- Tez Türü: Tıpta Uzmanlık
- Konular: Onkoloji, Üroloji, Oncology, Urology
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2011
- Dil: Türkçe
- Üniversite: Kocaeli Üniversitesi
- Enstitü: Tıp Fakültesi
- Ana Bilim Dalı: Üroloji Ana Bilim Dalı
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 82
Özet
Giriş:Prostat spesifik antijenin 90'larda kullanıma girmesi ile prostat adenocarcinoma (PCa) tanısı alan hasta sıklığı büyük oranda artmıştır. Lokalize PCa'lı hastalarda radyoterapi ve radikal prostatektomi dışında ayrıca aktif izlem (AS)'de kılavuzlarda tedavi alternatifleri arasında yerini almıştır. 5-? redüktaz inhibitörleri (5-ARI)'nin hem benign hem de kanserli prostat hücrelerinde apoptosise (programlı hücre ölümü) yol açtıkları bilinmektedir. Bu çalışmada AS hastalarda, 5-ARI'nın patolojik ilerleme üzerine etkilerini araştırmayı amaçladık.Gereç ve Yöntem:Şubat 2002 ?Nisan 2011 tarihleri arasında Kocaeli Üniversitesi Tıp Fakültesi Hastanesi Üroloji Kliniğinde, lokalize PCa tanısı ile AS (PSA?15 ng/ml, PSAD?0,20, ?cT2c, Gleason toplamı?3+3, kanserli örnek sayısı ?3, PCa için tedavi almamış) yapılan 69 hastanın dosyası geriye dönük kayıtlara dayalı olarak değerlendirmeye alındı. Tüm hastalara ilk iki yıl 3 ayda bir PSA kontrolü, 6 ayda bir parmakla rektal muayene (PRM), ikinci yıldan sonra 6 ay aralarla PSA kontrolü yapılmıştır. PSA yüksekliği veya anormal PRM varlığında hemen, aksi takdirde birinci yıl ve üçüncü ve yedinci yıl biyopsi tekrarı yapıldı. Tekrar biyopsilerinin histopatolojik incelemesinde kanser saptanan hastalarda Gleason toplamında, kanser saptanan örnek sayısında veya kanserli örnek kanser yüzdesinde artış olması patolojik ilerleme kabul edildi.İstatistiksel analizde sürekli değişkenler için t testi ve Wilcoxon rank-sum testi kullanıldı. Kategorik değişkenler için x2 testi kullanıldı. Patolojik ilerleme olması veya definitif tedavi uygulanmasına kadar geçen sürenin değerlendirilmesin Kaplan-Meier yöntemi, gruplar arası karşılaştırmalar ise Log-rank testi ile yapıldı.Patolojik ilerlemeyi öngörüde kullanılabilecek bağımsız faktörler, Cox proportional hazard metodu kullanılarak tek değişkenli ve çok değişkenli analiz yöntemleri ile değerlendirildi. Yapılan diğer tüm testlerde p değeri
Özet (Çeviri)
OBJECTIVESProstate adenocarcinoma (PCa) incidence is increased with the use of prostate specific antigen (PSA) which came into use in 90s. Active surveillance (AS) has become an alternative to radiotherapy (RT) and radical prostatectomy (RP) for the management of PCa. It is known that 5-? reductase inhibitors (5-ARI) cause apoptosis on both benign and cancerous prostate tissue. In this study, we aimed to investigate the impact of 5-ARI on pathological progression.PATIENTS AND METHODS:Records of 69 patients with PCa, who were included in AS (PSA?15ng/ml, PSAD?0.20, ?cT2c, Gleason sum?3+3, the number of cancer positive samples? 3, not treated for PCa) protocol between February 2002 and April 2011 were evaluated retrospectively. The follow up protocol included PSA testing quarterly and a digital rectal examination (DRE) biannually for the first 2 years, with a PSA control and DRE biannually after the 2nd year. Repeat biopsies were done for cause (increasing PSA, abnormal DRE) or periodically at the 1st, 3rd and 7th years. Pathological progression was defined as increasing Gleason grade and/or number of cores involved with carcinoma and/or percentage of cancer involvement on a single core.Wilcoxon rank-sum or t test was used for continuous variables, and categorical variables were evaluated with x2 test. Kaplan-Meier method and Log-rank test was used for survival analyses and to compare the differences between groups, respectively. End points used for survival analyses were the time of occurrence of pathological progression or the time at which definitive treatment was instituted. Univariable and multivariable cox proportional regression analysis was performed to assess the association of variables. p value less than 0.05 was considered statistically significant.RESULTSThe mean age of study cohort was 67±7.8, the mean and the median follow up was 31.7±18.2 and 26 (IQR:18-42), respectively. Forty-two percent of patients (29/69) were using 5-ARI for mean 34.4±16.7 and median 39 (IQR:23-45) months. Follow up for 58% (40/69) of patients without 5-ARI was mean 27.8±18.2 and median 23.5 (IQR:17-37.5) months. Pathological progression observed in 32% (22/69) of the patients, in mean 28.4±11.2 and median 25 (IQR:18-39) months. Pathological progression was observed at first repeat biopsy and at consequent repeat biopsies in 86.4% (19/22) and 13.6% (3/22), respectively. Mean and median follow up for patients without pathological progression (68%) was 33.2±20.6 and 27 (IQR:18-45) months, respectively.Twenty-eight patients were treated with one of the definitive treatment options (RT or RP) after mean 22.7±12.5, median 19.5 (IQR:14.5-35.5) months later. After a median follow up of 39 (IQR:23-46) months, 59.4% (41/69) of the patients were still on AS. Overall survival was 94.2% and none of the patients died because of PCa.Pathological progression was observed in 34.5% (10/29) of the patients using 5-ARI and 30% (12/40) of patients who did not use 5-ARI (p=0,693). Mean follow up for patients who used or did not use 5-ARI were 30.4±11 and 26.8±11.5 (Log-rank p=0.4151) months.Thirtyone % (9/29) of the patients who used 5-ARI versus 47.5% (19/40) of the patients who did not use have had definitive treatment. At the Kaplan-Meier analysis, patients who did not use 5-ARI treated significantly earlier (Log-rank p=0,0342). Regarding the median time to definitive treatment, a statistically significant difference was observed between the patients who used [24 months (IQR:20-39)] and did not use [17 months (IQR:9-32)] 5-ARI (p=0,0386). When the patients who had definitive treatment with their own decision were excluded (none of them were not on 5-ARI) no statistical significance was observed with respect to the 5-ARI usage for the time to definitive treatment (Log-rank p=0,276).On univariable analysis age, co-morbidities, clinical stage, lack of 5-ARI usage, PSAD, initial prostate volume, initial PSA, number of cancer positive biopsy cores were not associated with pathological progression. On multivariable analysis number of cancer positive biopsy cores was the strongest covariate associated with pathological progression (p=0.029). Age was associated with pathological progression (p=0,017), however, lack of 5-ARI usage was not (p=0,148). At repeat biopsies, Gleason sum 8-10 PCa was observed in 10.3% (3/29) of the patients who used and in 2.5% (1/40) of the patients who did not use 5-ARI (p=0,169).CONCLUSIONSIn this study pathological progression occurred mostly at first repeat biopsy. More than 2 cores of cancer positive at the initial biopsy was the strongest covariate associated with pathological progression. Therefore, regarding patient selection criteria, AS shouldn?t be offered to patients with more than 2 cores involved with cancer. There was no benefit of using 5-ARI for median 24 months to reduce pathological progression. A longer follow up period and prospective, randomized trials are needed to confirm these results.
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