ÖZET

Amaç:

Çalışmanın amacı, advers prognostik faktörlere sahip prostat kanserli hastalarda postoperatif adjuvan radyoterapi (ART) ve salvage radyoterapinin (SRT) onkolojik sonuçlara katkısını ve tedaviye bağlı yan etkileri değerlendirmektir.

Yöntem:

Ocak 2000-Ocak 2020 yılları arasında prostat kanseri tanısı alan ve açık veya robotic-assisted radikal prostatektomi sonrası kliniğimizde ART veya SRT uygulanan 105 hasta retrospektif olarak değerlendirilmiş ve takipleri devam eden 93 hasta çalışmaya dahil edilmiştir. Elli iki hastaya ART ve 41 hastaya da SRT tedavisi uygulanmıştır. Eksternal RT prostat yatağı medyan 70 Gy (66-72 Gy) ± pelvik lenfatiklere 50 Gy olacak şekilde uygulandı. Biyokimyasal nükssüz sağkalım (bPFS) ve tedaviye bağlı akut ve geç gastrointestinal (GI) ve genitoüriner (GU) toksisiteler değerlendirildi. bPFS ve tüm sağkalım ile ilişkili klinopatolojik değişkenleri analiz etmek ve yan etkileri değerlendirmek için Mann-Whitney U ve tek değişkenli analiz için ki-kare testi kullanıldı. Toksisite ile ilişkili risk faktörlerini araştırmak amacıyla çok değişkenli analiz için lojistik regresyon modeli kullanıldı.

Bulgular:

Çalışmaya dahil edilen hastaların medyan yaşı 64 (50-82) yıl idi. Tüm hasta popülasyonu için medyan takip süresi 30 ay (3-234 ay) idi. Postoperatif olarak cerrahi sınır pozitif, ekstrakapsüler ve seminal vesikül tutulumu olan advers patolojik özelliklere sahip 52 hastaya adjuvan RT uygulanırken, takip esnasında prostata özgü antijen düzeyi ≥0,2 ng/mL olan ve biyokimyasal nüks kabul edilen 41 hastaya SRT uygulandı. Üç yıllık bPFS ART kolunda %100 ve SRT kolunda %97,4 olarak tespit edildi. Akut ve geç yan etkiler Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer sistemine göre değerlendirildi ve ART ve SRT uygulanan hastalarda akut ve geç GI ve GU yan etkiler benzer bulundu. Akut toksisite gelişmesini predikte eden faktörlerin araştırıldığı çok değişkenli lojistik regresyon analizinde lenf nodu tutulumu olan (p=0,047) ve pelvik RT (WPRT) uygulanan hastalarda akut toksisite gelişme riski sadece prostat yatağı (PB) RT uygulananlara göre daha yüksek bulundu (p=0,002). Volümetrik arc tekniği kullanılarak (VMAT) uygulanan WPRT vs PB RT uygulanan hastalar karşılaştırıldığında, ≥grade 2 akut GI yan etki sırasıyla %4,2 ve %1,4 olarak tespit edilirken, ≥ grade 2 akut GU yan etki ise %12,5 ve %5,7 olarak bulundu (p=0,002). WPRT vs PB karşılaştırıldığında geç toksisite açısından istatistiksel olarak anlamlı bir fark bulunmadı.

Sonuç:

Postoperatif radyoterapi, kötü prognostik faktörü olan hastalarda bPFS’yi artırır. Postoperatif pelvik radyoterapiye bağlı yan etkilerin görülme sıklığı az olsa da, GI toksisite oranı belirgin derecede artmaktadır. VMAT gibi ileri tedavi teknikleri pelvik radyoterapinin yan etkilerini azaltmak için uygulanmalıdır. Hastaların hayat kalitesini artırmak için, zamanında uygulanan erken kurtarma radyoterapisi tedaviye bağlı yan etkileri azaltırken hastalık kontrolünü de artırır.

References

Kupelian PA, Potters L, Khuntia D, Ciezki JP, Reddy CA, Reuther AM, et al. Radical prostatectomy, external beam radiotherapy or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58(1):25-33.

Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT. Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol 2002;167(2 Pt 1):528-534.

Vargas C, Kestin LL, Weed DW, Krauss D, Vicini FA, Martinez AA. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features. Int J Radiat Oncol Biol Phys 2005;61(3):714-724.

Pisansky TM, Thompson IM, Valicenti RK, D’Amico AV, Selvarajah S. Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline Amendment 2018-2019. J Urol 2019;202(3):533-538.

Moghanaki D, Urdaneta AI, Karlin JD, Koontz BF, Anscher MS. Management of postprostatectomy biochemical relapse with salvage radiotherapy: results of an international survey. Am J Clin Oncol 2016;39(1):64-68.

Spiotto MT, Hancock SL, King CR. Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients. Int J Radiat Oncol Biol Phys 2007;69(1):54-61.

Abdollah F, Karnes RJ, Suardi N, Cozzarini C, Gandaglia G, Fossati N, et al. Impact of adjuvant radiotherapy on survival of patients with node-positive prostate cancer. J Clin Oncol 2014;32(35):3939-3947.

Bolla M, van Poppel H, Tombal B, Vekemans K, Pozzo LD, de Reijke TM, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: late results of a randomised controlled trial (EORTC trial 22911) Lancet 2012;380(9858):2018-2027.

Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: late followup of a randomized clinical trial. J Urol 2009;181(3):956-962.

Wiegel T, Bartkowiak D, Bottke D, Bronner C, Steiner U, Siegmann A, et al. Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 Trial. Eur Urol 2014;66(2):243-250.

Daly T, Hickey BE, Lehman M, Francis DP, See AM. Adjuvant radiotherapy following radical prostatectomy for prostate cancer. Cochrane Database Syst Rev 2011;(12):CD007234.

Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007;25(15):2035-2041.

Trock BJ, Han M, Freedland SJ, Humphreys EB, DeWeese TL, Partin AW, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 2008;299(23):2760-2769.

Cozzarini C, Fiorino C, Da Pozzo LF, Alongi F, Berardi G, Bolognesi A, et al. Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients. Int J Radiat Oncol Biol Phys 2012;82(1):191-199.

Sowerby RJ, Gani J, Yim H, Radomski SB, Catton C. Late complications in men who have early or late radiotherapy after radical prostatectomy. Can Urol Assoc J 2014;8(7-8):253-258.

Van Praet C, Ost P, Lumen N, De Meerleer G, Vandecasteele K, Villeirs G, et al. Postoperative high-dose pelvic radiotherapy for N+ prostate cancer: toxicity and matched case comparison with postoperative prostate bed-only radiotherapy. Radiother Oncol 2013;109(2):222-228.

Roach M, Marquez C, Yuo HS, Narayan P, Coleman L, Nseyo UO, et al. Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and gleason score in men with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 1994;28(1):33-37.

Michalski JM, Lawton C, El Naqa I, Ritter M, O’Meara E, Seider MJ, et al. Development of RTOG Consensus Guidelines for the Definition of the Clinical Target Volume for Postoperative Conformal Radiation Therapy for Prostate Cancer. Int J Radiat Oncol Biol Phys 2010;76(2):361-368.

Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31(5):1341-1346.

Thompson IM, Valicenti RK, Albertsen P, Davis BJ, Goldenberg SL, Hahn C, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol 2013;190(2):441-449.

Valicenti RK, Thompson I Jr, Albertsen P, Davis BJ, Goldenberg SL, Wolf JS, et al. Adjuvant and salvage radiation therapy after prostatectomy: American society for radiation oncology/american urological association guidelines. Int J Radiat Oncol Biol Phys 2013;86(5):822-828.

Shaikh MP, Alite F, Wu MJ, Solanki AA, Harkenrider MM. Adjuvant radiotherapy versus wait-and-see strategy for pathologic T3 or margin-positive prostate cancer: a meta-analysis. Am J Clin Oncol 2018;41(8):730-738.

Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol 2016;17(6):747-756.

Pearse M, Fraser-Browne C, Davis ID, Duchesne GM, Fisher R, Frydenberg M, et al. A phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the radiotherapy - adjuvant versus early salvage (RAVES) trial. BJU Int 2014;113 Suppl 2:7-12.

Parker C, Clarke N, Logue J, Payne H, Catton C, Kynaston H, et al. RADICALS Trial Management Group. RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery). Clin Oncol (R Coll Radiol) 2007;19(3):167-171.

Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, et al. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet 2020;396(10260):1422-1431.

Jereczek-Fossa BA, Zerini D, Vavassori A, Fodor C, Santoro L, Minissale A, et al. Sooner or later? Outcome analysis of 431 prostate cancer patients treated with postoperative or salvage radiotherapy. Int J Radiat Oncol Biol Phys 2009;74(1):115-125.

Feng M, Hanlon AL, Pisansky TM, Kuban D, Catton CN, Michalski JM, et al. Predictive factors for late genitourinary and gastrointestinal toxicity in patients with prostate cancer treated with adjuvant or salvage radiotherapy. Int J Radiat Oncol Biol Phys 2007;68(5):1417-1423.

Abugharib A, Jackson WC, Tumati V, Dess RT, Lee JY, Zhao SG, et al. Very early salvage radiotherapy improves distant metastasis-free survival. J Urol 2017;197(3 Pt 1):662-668.

Jackson WC, Schipper MJ, Johnson SB, Foster C, Li D, Sandler HM, et al. Duration of androgen deprivation therapy influences outcomes for patients receiving radiation therapy following radical prostatectomy. Eur Urol 2016;69(1):50–57.

Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 2005;294(10):1233-1239.

Riou O, Laliberte B, Azria D, Menkarios C, Moscardo CL, Dubois JB, et al. Implementing intensity modulated radiotherapy to the prostate bed:dosimetric study and early clinical results. Med Dosim 2013;38(2):117-121.

Ghadjar P, Hayoz S, Bernhard J, Zwahlen DR, Stein J, Hölscher T, et al. Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10. Radiother Oncol 2018;126(2):257-262.

Pollack A, Karrison TG, Balogh AG Jr, Low D, Bruner DW, Wefel JS, et al. Short term androgen deprivation therapy without or with pelvic lymph node treatment added to prostate bed only salvage radiotherapy: the NRG Oncology/RTOG 0534 SPPORT Trial. Int J Radiat Oncol Biol Phys 2018;102(5):1605.

Deville C, Vapiwala N, Hwang WT, Lin H, Bar Ad V, Tochner Z, et al. Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy. Int J Radiat Oncol Biol Phys 2012;82(4):1389-1396.

Radikal Prostatektomi Sonrası Adjuvan ve Kurtarma Radyoterapi Sonuçları

ÖZET

References