Mehmet UZUN, Eda ÇALIŞKAN YILDIRIM, Ferhat EKİNCİ, Bilgin DEMİR, Atike Pınar ERDOĞAN, Aziz KARAOĞLU, Hüseyin Salih SEMİZ

Metastatik Renal Hücreli Kanser Hastalarında Genel Sağkalım Üzerine Etkili Faktörlerin İncelenmesi: Dokuz Eylül Üniversitesi Tıbbi Onkoloji Kliniği Örneği

Amaç: Yeni nesil pek çok tedaviye rağmen oldukça kötü prognoza sahip metastatik renal hücreli karsinom (mRHK) tanılı hastalarda günümüze kadar kullanılan prognostik belirteçlerin her hastada prognozu doğru tayin edemediği bilinmektedir. Bu nedenle prognostik biyobelirteç arayışı sürmektedir. Bu çalışmada mRHK hastalarında tedavi öncesi biyokimyasal parametrelerin onkolojik sonuçlara etkisini araştırmak amaçlandı. Gereç ve Yöntemler: Kliniğimizde 2007-2020 tarihleri arasında tanı anında metastatik (Evre 4) veya lokal evrede (Evre 1-3) olup radikal nefrektomi yapılmış ve takipte nüks gelişen 90 mRHK hastasının klinik, patolojik, sağ kalım özellikleri ve sağ kalım üzerinde etkili olan faktörleri retrospektif olarak değerlendirildi. Hastaların demografik, klinikopatolojik ve tedavi özellikleri ile ilgili tanımlayıcı istatistiksel analizler yapıldı. Bulgular: Hastaların %21,2’i kadın, %78,8’si erkekti. Kadınlarla erkekler arasında medyan GS (genel sağkalım) açısından fark yoktu. Tanı anında metastazı olan hastalarda medyan GS süresi istatistiksel olarak anlamlı farkla daha düşüktü(p=0,001). Tanı anında metastatik hastalarda medyan GS 36,2 ay iken, takipte nüks olan hastalarda medyan GS 90,4 ay idi. Alkalenfosfataz/Albümin (ALP/ALB) oranı arttıkça sağkalım azalmaktaydı (p=0,038). CRP/ALB oranı 0.072 olanlarda bu süre 51 ay ile kısıtlıydı (AUC.630 p=0.046 cut off:0.072). Sonuç: CRP/ALB oranının prognozu belirleyen bir biyobelirteç olduğu saptanmıştır. Birinci sıra hedef tedavi sonrası progrese olan hastalarda immünoterapi önermekteyiz. Günümüzde özellikle mRHK'nin tedavi kararında prognoz önemli hâle gelmiştir ve yeni prognostik belirteçlerin araştırılmasına çalışmamızın ışık tutacağını düşünüyoruz.

Examination of Factors Affecting General Survival in Patients with Metastatic Renal Cell Cancer: A Case of Dokuz Eylül University Medical Oncology Clinic

Aim: Despite many new generation treatments, it is known that the prognostic markers used to date in patients with metastatic renal cell carcinoma (mRCC), who have a very poor prognosis, can not accurately determine the prognosis in every patient. Therefore, the search for prognostic biomarkers continues. In this study, it was aimed to investigate the effect of pre-treatment biochemical parameters on oncological outcomes in mRHC patients. Material and Methods: We retrospectively evaluated the clinical, pathological, survival characteristics and factors affecting survival of 90 mRCC patients who were metastatic (stage 4) or local (stage 1-3) at the time of diagnosis in our clinic, who underwent radical nephrectomy and relapsed during follow-up. Descriptive statistical analyzes of patients' demographic, clinicopathological and treatment characteristics were performed. Results: 21.2% of the patients were female and 78.8 % were male. There was no difference in median OS (overall survival) between women and men. The median OS duration was statistically significantly lower in patients with metastasis at the time of diagnosis (p=0.001). While the median OS was 36.2 months in metastatic patients at the time of diagnosis, the median OS was 90.4 months in patients with recurrence at follow-up. As the ratio of alkaline phosphatase/Albumin (ALP/ALB) increased, survival decreased (p=0.038). While the median OS of those with a CRP/ALB ratio of 0.072 (AUC.630 p=0.046 cut off:0.072). Conclusion: It has been determined that the CRP/ALB ratio is a biomarker that determines the prognosis. We recommend immunotherapy in patients who progress after first-linetargettherapy. Today, prognosis has become important especially in the treatment decision of mRCC, and we think that our study will shedlight on the search for new prognostic markers.

PDF

___

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
2. National Cancer Institute, Surveillance, Epidemiology, and End Results Program, Cancer Stat Facts: KidneyandRenalPelvisCancer.SEER 22 2015-2019:https:// seer.cancer.gov/statfacts/html/kidrp.html (01.02.2022)
3. Decastro GJ, McKiernan JM. Epidemiology, clinicalstaging, andpresentation of renalcellcarcinoma. Urol Clin North Am 2008;35:581-592.
4. Lipworth L, Tarone RE, McLaughlin JK. The epidemiology of renal cell carcinoma. J Urol 2006;176:2353-2358.
5. Bergström A, Hsieh CC, Lindblad P, Lu CM, Cook NR, Wolk A. Obesity and renal cell cancer--a quantitative review. Br J Cancer 2001;85:984-990.
6. Pischon T, Lahmann PH, Boeing H, Tjønneland A, Halkjaer J, Overvad K, Klipstein-Grobusch K, Linseisen J, Becker N, Trichopoulou A, Benetou V, Trichopoulos D, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Monninkhof E, Peeters PH, Bueno-de-Mesquita HB, Büchner FL, Ljungberg B, Hallmans G, Berglund G, Gonzalez CA, Dorronsoro M, Gurrea AB, Navarro C, Martinez C, Quirós JR, Roddam A, Allen N, Bingham S, Khaw KT, Kaaks R, Norat T, Slimani N, Riboli E. Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 2006;118(3):728-738.
7. Weikert S, Boeing H, Pischon T, Weikert C, Olsen A, Tjonneland A, Overvad K, Becker N, Linseisen J, Trichopoulou A, Mountokalakis T, Trichopoulos D, Sieri S, Palli D, Vineis P, Panico S, Peeters PH, Bueno-de-Mesquita HB, Verschuren WM, Ljungberg B, Hallmans G, Berglund G, González CA, Dorronsoro M, Barricarte A, Tormo MJ, Allen N, Roddam A, Bingham S, Khaw KT, Rinaldi S, Ferrari P, Norat T, Riboli E. Blood pressure and risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition. Am J Epidemiol 2008;167(4):438-446.
8. Babaoğlu AB, Tekindal M, Büyükuysal MÇ, Tözün M, Elmalı F, Bayraktaroğlu T, Tekindal MA. Epidemiyolojide Gözlemsel Çalışmaların Raporlanması: STROBE Kriterlerinin Türkçe Uyarlaması. Med J West Black Sea 2021;5:86-93.
9. Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, Mackenzie M, Wood L, Donskov F, Tan MH, Rha SY, Agarwal N, Kollmannsberger C, Rini BI, Choueiri TK. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population-based study. Lancet Oncol 2013;14:141-148.
10. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002;20:289-296.
11. Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P, Bukowski R. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 2005;23:832-841.
12. Kim JK, Kim SH, Song MK, Joo J, Seo SI, Kwak C, Jeong CW, Song C, Hwang EC, Seo IY, Lee H, Hong SH, Park JY, Chung J. Application of the international metastatic renal cell carcinoma database consortium and memorial Sloan Kettering Cancer Center risk models in patients with metastatic non- clear cell renal cell carcinoma: A multi-institutional retrospective study using the Korean Metastatic renal cell carcinoma registry. Cancer Res Treat 2019;51:758-768.
13. Saito K, Tatokoro M, Fujii Y, Iimura Y, Koga F, Kawakami S, Kihara K. Impact of c-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma. Eur Urol 2009;55:1145-1153.
14. Ito H, Shioi K, Murakami T, Takizawa A, Sano F, Kawahara T, Mizuno N, Makiyama K, Nakaigawa N, Kishida T, Miura T, Kubota Y, Yao M. C-reactive protein in patients with advanced metastatic renal cell carcinoma: Usefulness in identifying patients most likely to benefit from initial nephrectomy. BMC Cancer 2012;12:337.
15. Fukuda H, Takagi T, Kondo T, Yoshida K, Shimizu S, Nagashima Y, Tanabe K. Prognostic value of the Glasgow Prognostic Score for patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy. Int J Clin Oncol 2018;23(3):539- 546.
16. Lamb GW, Aitchison M, Ramsey S, Housley SL, McMillan DC. Clinical utility of the Glasgow Prognostic Score in patients undergoing curative nephrectomy for renal clear cell cancer: Basis of new prognostic scoring systems. Br J Cancer 2012;106:279-283.
17. Day D, Kanjanapan Y, Kwan E, Yip D, Lawrentschuk N, Davis ID, Azad AA, Wong S, Rosenthal M, Gibbs P, Tran B. Benefit from cytoreductive nephrectomy and the prognostic role of neutrophil-to-lymphocyte ratio in patients with metastatic renal cell carcinoma. Intern Med J 2016;46:1291-1297.
18. Keizman D, Ish-Shalom M, Huang P, Eisenberger MA, Pili R, Hammers H, Carducci MA. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer 2012;48:202-208.
19. Ishihara H, Kondo T, Yoshida K, Omae K, Takagi T, Iizuka J, Tanabe K. Effect of systemic inflammation on survival in patients with metastatic renal cell carcinoma receiving second- line molecular-targeted therapy. Clin Genitourin Cancer 2017;15(4):495-501.
20. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang YH, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T; KEYNOTE-426 Investigators. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380:1116-1127.
21. Thompson RH, Ordonez MA, Iasonos A, Secin FP, Guillonneau B, Russo P, Touijer K. Renal cell carcinoma in young and old patients--is there a difference? J Urol 2008;180:1262-1266.
22. Aron M, Nguyen MM, Stein RJ, Gill IS. Impact of gender in renal cell carcinoma: An analysis of the SEER database. Eur Urol 2008;54:133-140.
23. Toyoda Y, Shinohara N, Harabayashi T, Abe T, Akino T, Sazawa A, Nonomura K. Survival and prognostic classification of patients with metastatic renal cell carcinoma of bone. Eur Urol 2007;52(1):163-168.
24. Hasbek Z, Gül SS, Turgut B. Kanserli hastalarda alkalen fosfataz düzeyi ile kemik sintigrafisinde tespit edilen lezyon sayısı arasındaki ilişkinin değerlendirilmesi. Çağdaş Tıp Dergisi 2014;4:128-132.