Öz
Amaç
Bu retrospektif, tek merkezli çalışma, metastatik renal hücreli karsinom (RCC) tanılı hastalarda immünoterapi (İO) ve İO kombinasyonu veya İO ile tirozin kinaz inhibitörü (TKİ) tedavilerinin (İO+İO veya İO+TKİ) etkinliğini ve prognostik faktörleri değerlendirmeyi amaçlamıştır.
Yöntem
2022-2025 yılları arasında İstanbul Medipol Üniversitesi Tıbbi Onkoloji Kliniği’nde metastatik RCC tanısı ile birinci basamakta İO+İO veya İO+TKİ kombinasyon tedavisi alan 24 hasta incelendi. Hastaların demografik ve klinikopatolojik özellikleri ile tedavi yanıtları değerlendirildi. Progresyonsuz sağkalım (PFS) ve genel sağkalım (OS) analizleri Kaplan-Meier ve Cox regresyon modelleri kullanılarak yapıldı. Sağkalımlar üzerine etkili prognostik faktörler analiz edildi.
Bulgular
Hastaların çoğu erkekti (%79,2) ve ortanca yaş 56 yıldı. En sık metastaz bölgeleri lenf nodu (%63) ve akciğer (%50,3) idi. Hastaların büyük çoğunluğu berrak hücreli karsinom histolojisine sahipti (%83,3). Tedavi yanıtları %16,7 tam yanıt, %62,5 kısmi yanıt, %12,5 stabil hastalık ve %8,3 progresif hastalık (PD) olarak gözlendi. Böylece, objektif yanıt oranı %79,2 olarak bulundu. Medyan genel sağkalım (OS) 41,8 ay, medyan PFS 25,87 ay olarak hesaplandı. Tek değişkenli analizde tanı evresi, histoloji, ve nefrektomi varlığı PFS için anlamlı bulunurken, çok değişkenli analizde sadece tanı evresi bağımsız prognostik faktör olarak belirlendi (p=0,03, tehlike oranı: 5,64). OS için tek değişkenli analizde ise, tanı evresi, histoloji ve nefrektomi varlığı anlamlı iken, çok değişkenli analizde herhangi bir bağımsız prognostik faktör bulunamadı.
Sonuç
Metastatik RCC’de İO+İO veya İO+TKİ kombinasyon tedavileri yüksek yanıt oranları ve uzun sağkalım süreleri ile ilişkilidir. Tanı anındaki evre PFS için bağımsız prognostik faktördür. Bu faktör, hastaların prognozunu değerlendirmede ve tedavi kararlarını kişiselleştirmede kritik öneme sahiptir.
Anahtar Kelimeler:
Birinci basamak tedavi, immünoterapi, metastatik renal hücreli karsinom, sağkalım, tirozin kinaz inhibitörleri, yan etkiler
Kaynaklar
1
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
2
Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. (2024). Global cancer observatory: cancer today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today.
3
Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, et al. Epidemiology of renal cell carcinoma. Eur Urol. 2019;75(1):74-84.
4
Cheung CY, Chan GC, Chan SK, Ng F, Lam MF, Wong SS, et al. Cancer incidence and mortality in chronic dialysis population: a multicenter cohort study. Am J Nephrol. 2016;43(3):153-159.
5
Chow WH, Gridley G, Fraumeni JF, Järvholm B. Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med. 2000;343(18):1305-1311.
6
Pesch B, Haerting J, Ranft U, Klimpel A, Oelschlägel B, Schill W. Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC study group. Multicenter urothelial and renal cancer study. Int J Epidemiol. 2000;29(6):1014-1024.
7
Henschler D, Vamvakas S, Lammert M, Dekant W, Kraus B, Thomas B, et al. Increased incidence of renal cell tumors in a cohort of cardboard workers exposed to trichloroethene. Arch Toxicol. 1995;69(5):291-299.
8
Hakimi AA, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, et al. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst. 2013;105(24):1862-1870.
9
Arnold M, Pandeya N, Byrnes G, Renehan PAG, Stevens GA, Ezzati PM, et al. Global burden of cancer attributable to high bodymass index in 2012: a population-based study. Lancet Oncol. 2015;16(1):36-46.
10
Al-Ahmadie HA, Alden D, Qin LX, Olgac S, Fine SW, Gopalan A, et al. Carbonic anhydrase IX expression in clear cell renal cell carcinoma: an immunohistochemical study comparing 2 antibodies. Am J Surg Pathol. 2008;32(3):377-382.
11
Moch H, Amin MB, Berney DM, Compérat EM, Gill AJ, Hartmann A, et al. The 2022 World Health Organization classification of tumours of the urinary system and male genital organs-part a: renal, penile, and testicular tumours. Eur Urol. 2022;82(5):458-468.
12
Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol. 2004;22(24):4991-5004.
13
Carlo MI, Mukherjee S, Mandelker D, Vijai J, Kemel Y, Zhang L, et al. Prevalence of germline mutations in cancer susceptibility genes in patients with advanced renal cell carcinoma. JAMA Oncol. 2018;4(9):1228-1235.
14
Skinner DG, Colvin RB, Vermillion CD, Pfister RC, Leadbetter WF. Diagnosis and management of renal cell carcinoma: a clinical and pathologic study of 309 cases. Cancer. 1971;28(5):1165-1177.
15
Loughlin KR. The great masquerader’s new wardrobe in the modern era: the paraneoplastic manifestations of renal cancer. Urol Clin North Am. 2023;50(2):305-310.
16
Moldovan T, Boynton D, Kuperus J, Parker J, Noyes SL, Brede CM, et al. Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma. Urol Oncol. 2023;41(9):392.e11-392.e17.
17
Pallagani L, Choudhary GR, Himanshu P, Madduri VKS, Singh M, Gupta P, et al. Epidemiology and clinicopathological profile of renal cell carcinoma: a review from tertiary care referral centre. J Kidney Cancer VHL. 2021;8(1):1-6.
18
Kim HL, Belldegrun AS, Freitas DG, Bui MH, Han KR, Dorey FJ, et al. Paraneoplastic signs and symptoms of renal cell carcinoma: implications for prognosis. J Urol. 2003;170(5):1742-1746.
19
Patel HD, Gupta M, Joice GA, Srivastava A, Alam R, Allaf ME, et al. Clinical stage migration and survival for renal cell carcinoma in the United States. Eur Urol Oncol. 2019;2(4):343-348.
20
Cheaib JG, Patel HD, Johnson MH, Gorin MA, Haut ER, Canner JK, et al. Stage-specific conditional survival in renal cell carcinoma after nephrectomy. Urol Oncol. 2020;38(1):6.e1-6.e7.
21
Ficarra V, Righetti R, Pilloni S, D’amico A, Maffei N, Novella G, et al. Prognostic factors in patients with renal cell carcinoma: retrospective analysis of 675 cases. Eur Urol. 2002;41(2):190-198.
22
Palumbo C, Pecoraro A, Knipper S, Rosiello G, Luzzago S, Deuker M, et al. Contemporary age-adjusted incidence and mortality rates of renal cell carcinoma: analysis according to gender, race, stage, grade, and histology. Eur Urol Focus. 2021;7(3):644-652.
23
Pierorazio PM, Johnson MH, Ball MW, Gorin MA, Trock BJ, Chang P, et al. Five-year analysis of a multi-institutional prospective clinical trial of delayed intervention and surveillance for small renal masses: the DISSRM registry. Eur Urol. 2015;68(3):408-415.
24
Dudani S, de Velasco G, Wells JC, Gan CL, Donskov F, Porta C, et al. Evaluation of clear cell, papillary, and chromophobe renal cell carcinoma metastasis sites and association with survival. JAMA Netw Open. 2021;4(1):e2021869.
25
Duarte C, Hu J, Beuselinck B, Panian J, Weise N, Dizman N, et al. Metastatic renal cell carcinoma to the pancreas and other sites-a multicenter retrospective study. EClinicalMedicine. 2023;60:102018.
26
Ernst MS, Navani V, Wells JC, Donskov F, Basappa N, Labaki C, et al. Outcomes for international metastatic renal cell carcinoma database consortium prognostic groups in contemporary first-line combination therapies for metastatic renal cell carcinoma. Eur Urol. 2023;84(1):109-116. Erratum in: Eur Urol. 2023;83(6):e166-e167.
27
Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794-5799.
28
Rose TL, Kim WY. Renal cell carcinoma: a review. JAMA. 2024;332(12):1001-1010.
29
Appleman LJ, Kim SE, Harris WB, Pal SK, Pins MR, Kolesar J, et al. Randomized, double-blind phase III study of pazopanib versus placebo in patients with metastatic renal cell carcinoma who have no evidence of disease after metastasectomy: ECOG-ACRIN E2810. J Clin Oncol. 2024;42(17):2061-2070.
30
Buchbinder EI, Dutcher JP, Daniels GA, Curti BD, Patel SP, Holtan SG, et al. Therapy with high-dose interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition. J Immunother Cancer. 2019;7(1):49.
31
Fishman M, Dutcher JP, Clark JI, Alva A, Miletello GP, Curti B, et al. Overall survival by clinical risk category for high dose interleukin-2 (HD IL-2) treated patients with metastatic renal cell cancer (mRCC): data from the PROCLAIM SM registry. J Immunother Cancer. 2019;7(1):84.
32
Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthélémy P, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020;5(6):e001079.
33
Tannir NM, Escudier B, McDermott DF, Burotto M, Choueiri TK, Hammers HJ, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): long-term follow-up data from the phase 3 CheckMate 214 trial. J Clin Oncol. 2024;42(4):363.
34
Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300.
35
Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841.
36
Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116-1127.
37
Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, et al. Sunitinib alone or after nephrectomy in metastatic renalcell carcinoma. N Engl J Med. 2018;379(5):417-427.
38
Motzer RJ, Banchereau R, Hamidi H, Powles T, McDermott D, Atkins MB, et al. Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade. Cancer Cell. 2020;38(6):803-817.e4.
