Lokal Hastalıkta Küratif Tedavi Sonrası Hangi Hastalar Adjuvan Tedaviye Adaydır? Dr.Feyyaz ÖZDEMİR K.T.Ü Tıbbi Onkoloji B.D. EHOK-2015
Kanser Olguları: 2013
Kanserden Ölüm Olguları: 2013
Hayat Boyu Görülme Riski: 2009 Bölge Erkek Bayan Tüm bölgeler 44% 38% Meme 12.4% Kolorektal 5.17% 4.78% AC 7.8% 6.4% Melanoma 2.9% 1.9% Prostat 16.2%
Ölüm Riski: 2009 Bölge Erkek Bayan Tüm Bölge 23.5% 19.9% Meme 2.9% Kolorektal 2.3% 2.2% AC 7.8% 4.9% Melanoma 0.35% 0.20% Prostat 2.97%
Erkeklerde Kanser Mortalite Oranları: 1930 to 2009 lung stomach colorectal prostate
Tanı ve Ölümde Medyan Yaş 80 78 76 74 72 70 68 66 64 62 60 Diagnosis Death Lung Colon All Breast Prostate 13 yıllık fark
Adjuvant Tedavi Seçenekleri
Adjuvant Tedavi Seçenekleri 1.RT
1-PostOp Radiation (Adjuvant Tedavi) patolojik olarak kanser komplet şekilde çıkarılmışsa 2-Salvage Radiation patolojik olarak kanser komplet şekilde çıkarılmışsa
Adverse Özellikler 1.Positif Cerrahi Marjin-ler 2.Seminal Vesiküllere İnvazyon 3.Extrakapsüler Yayılım 4.Detectable PSA (Cerrahi sonrası birkaç hafta içinde PSA undetectable seviyeye inmelidir)
PROSTATE CAPSULE Seminal Vesicles
Patolojik Positive Cerrahi Marjin PSA Relapsı Risk Group + Margins - Margins Low risk 5.1% 0.4% Intermediate 17% 6.5% High 43% 21.5% J Urol. 2010;183(1):145.
Positive Cerrahi Marjinin Etkileri 3 Yıl İçindeki PSA Relapsı Soliter Apical Margin 13.0% Soliter Non-apical margin 18.6% Multipl positive marginler 27.0%
Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. Stamey TA After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. N Engl J Med. 1987 Oct 8;317(15):909-16. Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy. Oesterling JE the half-life of prostate specific antigen was calculated to be 3.15 days. J Urol. 1988 Apr;139(4):766-72
PSA Yarı Ömrü: 3 gün Surgery 6 12 Percentage 3 days 3 6 50% 6 days 1.5 3 25% 9 days.75 1.5 12.5% 12 days.375.75 6.25% 15 days.1875.375 3.125% 18 days.0937.1875 1.5625% 21 days.0468.0937.0078% 24 days.0234.0468.0039% 27 days.0117.0234.0019% 30 days.0059 (<0.01).0017.00098% 33 days.0029 (<0.01).0059 (<0.01).00049% Undetectable (<0.01) seviyeye ulaşmak 4,5 hafta alabilir. Kontrol PSA ya 6-8 haftalarda genellikle bakılır.
PostOp Radyasyon işe yarıyor mu? SWOG 8794 (n:425) EORTC (n:1005) 10 Yıllık PSA Cure Oranı (seminal vesicle) Cerrahi 12% Cerrahi+ Adj.RT 36% 5 Yıllık Cure Oranı (Positive Marjin) Cerrahi 49% Cerrahi+Adj.RT 78% German Study (Wiegel, n:268) 5 Yıllık Cure Oranı ( T3 tm) Cerrahi 54% Cerrahi+Adj.RT 72%
Yüksek Riskli Hastalarda PostOp Radyoterapinin Avantajı RT RT RT No RT No RT No RT
T3 undetectable PSA lı Hastalarda PostOp RT ile Cure Oranları
Yüksek Risk Özellikleri Olanlarda PostOp RT mi yoksa Bekle ve Daha Sonra RT (PSA yükselmeye başlayınca-salvage)? 415 hasta Cozzarini. IJROBP 2004;59:674 8 Yıllık Sağkalım Erken RT Salvage Positive Marjin 91% 67% Extra-kapsular Yayılım 92% 75% Gleason 7 88% 72% Node Metastazı 88% 68%
Adjuvant Tedavi Seçenekleri 1.RT
Adjuvant Tedavi Seçenekleri 1.RT 2.Observasyon
Advers Özellik Taşıyan Radikal Prostatektomili Hastalara Adjuvant Radiotherapy: A Randomized Clinical Trial. 425 Hasta Randomize RT 60-64 Gy prostatic fossaya (n = 214) Observation (n = 211). Endpoint Cerrahi+Observasyon Cerrahi+ RT Metastatic free Survival 13.2 years 14.7 years Overall Survival 13.8 years 14.7 years Yan Etkiler 11.9% 23.8% rektal komplikasyonlar 0% 3.3% striktürler 9.5% 17.8% inkontinans 2.8% 6.5% Ian M. Thompson, Jr, MD; JAMA. 2006;296:2329-2335
PostOp Radyoterapi NCCN Önerisi RP (radical prostatectomy) PLND (pelvic lymph node dissection) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
NCCN Önerisi: PostOp RT RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
NCCN Önerisi: Advice on PostOp Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
Salvage Radiation: Cerrahi sonrası eğer aylar veya yıllar sonra PSA tekrar yükselmeye başlarsa uygulanır.
Salvage Radyasyon...işe yarıyormu? Patoloji Gleason? Cerrahi marjin temiz mi? Seminal vesikül veya lymph nodes? Extra-capsular yayılım? Cerrahi yapılalı ne kadar oldu? PSA yükselme hızı(doubling time)? RT uygulanacak zaman sırasındaki PSA seviyesi? Uygulanacak Radyasyon Dozuna? Bağlı
Salvage RT nin Gleason Skoruna göre PSA Cure Oranları Gleason 2-6 Gleason 7 Gleason 8-10 Time in Months
RT Uygulandığı Zamanki PSA Seviyesine Göre Cure Oranları prostate-specific antigen 0.50 veya daha az (mavi), 0.51-1.00 (sarı), 1.01-1.50 (gri), ve 1.50 ng/ml dan yüksekse (kırmızı) J Clin Oncol. 2007 May 20;25(15):2035-41.
PSA yükseliş hızı düşükse Salvage (postop) RT daha başarılı
RT dozu yüksekse Salvage (postop) RT daha başarılı
Salvage Radiation Sağkalımı Uzatır mı? Mayo (2657) 10 yıllık mortalite de azalma yok (70% vs 69%) Hopkins (635) 10 yıllık mortalite azalmış 86% vs 62% Duke (519) Tüm sebeplere bağlı mortalitede azalma var. (11 yılda %47 azalma var) J Urol. 2009;182(6):2708 JAMA. 2008;299(23):2760.
NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
NCCN Önerisi: Salvage Radyasyon RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron) PSADT (PSA doubling time)
NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
RT Tekniklerinde İlerlemeler
After IMRT was established then IGRT (image guided) was introduced
Lower Risk of Side Effects with Image Guided IMRT compared to IMRT
Better Cure Rates with Image Guided IMRT compared to IMRT for Prostate Intermediate Risk High Risk
Post-Prostatektomi RT (NCCN) Positive marginli ve yavaş PSA doubling time (>9 months) lı hastalar en çok PostOp RT den faydalanan hastalardır. Salvage RT den en çok, undetectable PSA yı takip eden 2 ölçümde detectable hale gelirse, yavaş PSA doubling time lı ve hala 1 den az PSA varsa faydalanır. Önerilen dozu: 64-70Gy Hedef prostate yatağı ve lenf nodlarını içermelidir. (Tüm pelvis değil)
http://www.mskcc.org/cancer-care/adult/prostate/prediction-tools
http://nomograms.mskcc.org/prostate/salvageradiationtherapy.aspx
http://nomograms.mskcc.org/prostate/salvageradiationtherapy.aspx
Adjuvant Tedavi Seçenekleri 1.RT 2.Observasyon
Adjuvant Tedavi Seçenekleri 1.RT 2.Observasyon 3.ADT
NCCN Advice on PostOp Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)
Radikal Prostatektomi ve Pelvik Lenfadenektomi (node-positive prostate cancer) Uygulanmış Hastalarda Erken Vs Ertelenmiş androgen deprivation treatment Lancet Oncology Volume 7, Issue 6, June 2006, Pages 472 479 ABD de 36 merkez 1988 93 yılları arasında ADT (n=47) veya observasyon (n=51) Median follow-up 11.9 yıl, Erken ADT grubunda overall survival (hazard ratio 1.84 p=0.04), prostate-cancer-specific survival (4.09 p=0.0004), ve progression-free survival (3.42, p<0.0001) avantajı tespit edildi.
Adjuvant Tedavi Seçenekleri 1.RT 2.Observasyon 3.ADT
Adjuvant Tedavi Seçenekleri 1.RT 2.Observasyon 3.ADT 4.KT
Pilot çalışma: Yüksek riskli PC li hastalarda adjuvant paclitaxel + estramustine Prostatektomy Paclitaxel haftalık x 3 siklus 17 hasta PSA failure a kadar geçen zaman 19 ay. Historik kontrole göre anlamlı. 2008 Catmar JP Urology
Docetaxel-estramustine in localized high-risk prostate cancer: Results of the French Genitourinary Tumor Group GETUG 12 phase III trial. 2014 ASCO Annual Meeting Karim Fizazi, Agnes Laplanche, Francois Lesaunier, Remy Delva Methods: Eligibility included non-pretreated high-risk localized CaP, defined as 1 of the following criteria: T3-T4, Gleason score (GS) 8, PSA 20 ng/ml, pn+ (stratification factors). All pts had a staging pelvic lymph node dissection. Pts were randomly assigned to either goserelin 10.8 mg every 3 months for 3 years and 4 cycles of docetaxel 70 mg/m 2 q3w + estramustine 10 mg/kg/d d1-5 (ADT+DE arm) or goserelin alone (ADT arm). Local therapy was administered at 3 months. The primary endpoint is progressionfree survival (PFS); events=psa relapse, radiographic relapse, death. The planned number of pts was 400, to detect a 12% difference at 4 years with a power of 80% and a type I error of 0.05 (two-sided Logrank test). Preliminary results indicated a better PSA response rate (PSA 0.2 ng/ml: 34% in the ADT+DE arm vs 15% in the ADT arm [p< 0.0001]), neutropenic fever in 2%, and no negative impact on QoL at 1 year in the ADT+DE arm (Fizazi, Eur J Cancer 2012; 48:209-17). Here we report PFS results. Results: 413 pts were accrued. With a median follow-up of 7.6 years, PFS was marginally improved in the ADT+DE arm: 8-year PFS rate: 62% [55 69] in the ADT+DE arm vs 53% [45 60] in the ADT arm (adjusted HR: 0.75 [0.55-1.01], p=0.06). In pts with a GS<8, the 8-year PFS rate was 69% [60-78] (ADT+DE) and 51% [41-61] (ADT) (HR: 0.55 [0.36-0.84], interaction test =0.06 for GS). A non-significant trend favoring ADT+DE was found for clinical PFS (HR: 0.79 [0.55-1.13]). No long-term toxicity signal was detected, with no toxic death. The 8-year cumulative incidence of second cancers (11% vs 10%) was similar in the two arms. The 8-year OS rate is 83% [77 89] with no difference between treatment arms (HR: 0.94 [0.60-1.49]). In pts with a GS<8, the 8-year OS rate was 94% [89-98] (ADT+DE) and 85% [78-92] (ADT) (HR: 0.40 [0.17-0.91], interaction test: p=0.02). Conclusions: Docetaxel-estramustine is associated with a
Teşekkürler