Sarkomatoid RHK tanılı hastaların uzun dönemli takip sonuçları: Tek merkez deneyiminin retrospektif değerlendirmesi

Öz

Amaç: Sarkomatoid renal hücreli kanser (sRHK) oldukça nadir bir durum olup, hastalık yönetimi ile ilgili literatür verisi kısıtlıdır. Yüksek kalitede veriye dayanan tedavi önerileri yoktur. Bu çalışmadaki amacımız, sRHK tanılı hastalarımızdaki uzun süreli tecrübemizi ortaya koymaktır. Yöntemler: sRHK tanısıyla Ocak 2010-Aralık 2019 arasında takip edilen hastalar, genel hastalık özellikleri, verilen tedaviler, tedavi yanıtları ve sağ kalım süreleri açısından retrospektif olarak değerlendirildi. Bulgular: Üç yüz on bir RCC hastasının 25'inde (%8,0) sarkomatoid farklılaşma gözlendi. Çalışmaya dahil edilen 25 hastanın ortanca yaşları 58,1 (26,3-78,0)’di ve büyük çoğunluğu erkekti (n=18, 72%). Tanı anında 11 (%44,0) hastada uzak organ metastazı vardı. Küratif cerrahi yapılan 14 hastanın 10’unda (%71,4) uzak organ metastazı ile nüks izlendi. Metastatik 21 hastanın 13 (%61,9)’ü ikinci basamak tedavide tirozin kinaz inhibitörü (pazopanib veya sunitinib) aldı. Bu 13 hastanın ikinci basamak tedavisi için progresyonsuz sağ kalım süresi 6,1 aydı (%95 CI: 3,8-8,4). Nivolumab tedavisi alan 2 hastadan birinde uzun süreli hastalık kontrolü sağlandı. Tanı anında metastatik evrede olan 11 hastanın 7 (%63,6)’sinde sitoredüktif cerrahi uygulandı. Pulmoner metastazektomi yapılan 2 hastadan biri metastazektomi sonrası 112.ayda hala nükssüz izlenmekteydi. Metastatik evredeki toplam 21 hasta için genel sağ kalım süresi 10,8 aydı (%85 CI: 8,9-12,6). Sonuç: Sarkomatoid RCC oldukça nadir görülen ve kötü prognoza sahip bir hastalıktır. Hastaların çoğunda uzak organ metastazı gözlenmekle birlikte sistemik tedavi etkinliği düşüktür. Güncel tedavi yöntemleri içinde tirozin kinaz inhibitörleri ön plandadır. Yeni nesil tedavi seçeneklerinden olan immun kontol noktası inhibitörleri tedavi başarısı açısından ümit vaat etmektedir. Sitoredüktif nefrektomi ve metastazektominin tedaviye eklenmesi ek faydalar sağlayabilir.

Anahtar Kelimeler

• RHK
• sarkomatoid diferansiyasyon
• sRHK
• TKİ
• nivolumab
• sitoredüktif nefrektomi

Long-term follow-up results of patients with sarcomatoid RCC: A retrospective evaluation of a single center experience

Abstract

Aim: Sarcomatoid renal cell cancer (sRCC) is an extremely rare condition, and literature on disease management is limited. There are no treatment recommendations based on high-quality data. Our aim in this study is to reveal our long-term experience with patients diagnosed with sRCC. Methods: Patients who were followed up with a diagnosis of sRCC between January 2010 and December 2019 were retrospectively evaluated in terms of main disease characteristics, treatments, treatment responses and survival times. Results: Twenty-five (8.0%) of 311 RCC patients had sarcomatoid differentiation. The median age of the 25 patients included in the study was 58.1 (26.3-78.0) years, and the vast majority were male (n=18, 72%). Distant organ metastasis was present in 11 (44.0%) patients at the time of diagnosis. In 10 (71.4%) out of 14 patients who underwent curative surgery, recurrence was observed with distant organ metastasis. Thirteen (61.9%) of 21 metastatic patients received tyrosine kinase inhibitor (pazopanib or sunitinib) in second-line treatment. The progression-free survival for the second line treatment of these 13 patients was 6.1 months (95% CI: 3.8-8.4). Long-term disease control was achieved in one of the two patients who received nivolumab treatment. Cytoreductive nephrectomy was performed in seven (63.6%) of the 11 patients who were in metastatic stage at the time of diagnosis. Pulmonary metastasectomy was performed in two patients with lung metastasis. One of these two patients was still followed up without recurrence at the 112th month after metastasectomy. Overall survival was 10.8 months (85% CI: 8.9-12.6) for 21 patients in the metastatic stage. Conclusion: sRCC is a rare disease with a poor prognosis. Systemic treatment efficacy is low with frequent distant metastases. Tyrosine kinase inhibitors are prominent among current treatment methods. Immune checkpoint inhibitors, one of the new generation treatment options, is promising in terms of treatment success. The addition of cytoreductive nephrectomy and metastasectomy to the treatment process may provide additional benefits.

Keywords

• RCC
• sarcomatoid differentiation
• sRCC
• TKI
• nivolumab
• cytoreductive nephrectomy

References

1. 1. Farrow GM, Harrison Jr EG, Utz DC. Sarcomas and sarcomatoid and mixed malignant tumors of the kidney in adults—part III. Cancer. 1968;22(3):556-63.
2. 2. Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, et al. The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. The American journal of surgical pathology. 2013;37(10):1490-504.
3. 3. de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, et al. Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases. The American journal of surgical pathology. 2001;25(3):275-84.
4. 4. Cheville JC, Lohse CM, Zincke H, Weaver AL, Leibovich BC, Frank I, et al. Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome. The American journal of surgical pathology. 2004;28(4):435-41.
5. 5. Shuch B, Said J, LaRochelle JC, Zhou Y, Li G, Klatte T, et al. Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2010;116(3):616-24.
6. 6. Kwak C, Park YH, Jeong CW, Jeong H, Lee SE, Moon KC, et al. Sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma. Journal of surgical oncology. 2007;95(4):317-23.
7. 7. Keskin SK, Msaouel P, Hess KR, Yu K-J, Matin SF, Sircar K, et al. Outcomes of patients with renal cell carcinoma and sarcomatoid dedifferentiation treated with nephrectomy and systemic therapies: comparison between the cytokine and targeted therapy eras. The Journal of urology. 2017;198(3):530-7.
8. 8. Haas NB, Lin X, Manola J, Pins M, Liu G, McDermott D, et al. A phase II trial of doxorubicin and gemcitabine in renal cell carcinoma with sarcomatoid features: ECOG 8802. Medical Oncology. 2012;29(2):761-7.

9. 9. Lebacle C, Pooli A, Bessede T, Irani J, Pantuck AJ, Drakaki A. Epidemiology, biology and treatment of sarcomatoid RCC: current state of the art. World journal of urology. 2019;37(1):115-23.
10. 10. National Comprehensive Cancer Network: NCCN Practice Guidelines in Oncology.Kidney Cancer. Version 1.2021.
11. 11. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2016;27(suppl_5):v58-v68.
12. 12. Mian BM, Bhadkamkar N, Slaton JW, Pisters PW, Daliani D, Swanson DA, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. The Journal of urology. 2002;167(1):65-70.
13. 13. Kyriakopoulos CE, Chittoria N, Choueiri TK, Kroeger N, Lee J-L, Srinivas S, et al. Outcome of patients with metastatic sarcomatoid renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Clinical genitourinary cancer. 2015;13(2):e79-e85.
14. 14. Merrill MM, Wood CG, Tannir NM, Slack RS, Babaian KN, Jonasch E, et al., editors. Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: Natural history and outcomes after surgical resection with curative intent. Urologic Oncology: Seminars and Original Investigations; 2015: Elsevier.
15. 15. Nanus DM, Garino A, Milowsky MI, Larkin M, Dutcher JP. Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer. 2004;101(7):1545-51.
16. 16. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Wagstaff J, Salman P, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. Journal of clinical oncology. 2010.
17. 17. Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. European journal of cancer. 2013;49(6):1287-96.
18. 18. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. New England Journal of Medicine. 2007;356(2):115-24.
19. 19. Méjean A, Ravaud A, Thezenas S, Colas S, Beauval J-B, Bensalah K, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. New England Journal of Medicine. 2018;379(5):417-27.
20. 20. Silagy AW, Mano R, Blum KA, DiNatale RG, Marcon J, Tickoo SK, et al. The Role of Cytoreductive Nephrectomy for Sarcomatoid Renal Cell Carcinoma: A 29-Year Institutional Experience. Urology. 2020;136:169-75.
21. 21. Hofmann H-S, Neef H, Krohe K, Andreev P, Silber R-E. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. European urology. 2005;48(1):77-82.
22. 22. Ueno T, Yamashita M, Sawada S, Sugimoto R, Nishijima N, Sugawara Y, et al. Pulmonary metastasectomy from renal cell carcinoma including 3 cases with sarcomatoid component. General thoracic and cardiovascular surgery. 2016;64(3):149-52.
23. 23. Joseph RW, Millis SZ, Carballido EM, Bryant D, Gatalica Z, Reddy S, et al. PD-1 and PD-L1 expression in renal cell carcinoma with sarcomatoid differentiation. Cancer immunology research. 2015;3(12):1303-7.
24. 24. Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer research. 2006;66(7):3381-5.
25. 25. McKay RR, McGregor BA, Gray K, Steinharter JA, Walsh MK, Braun DA, et al. Results of a phase II study of atezolizumab and bevacizumab in non-clear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (sccRCC). Journal of Clinical Oncology. 2019;37(7_suppl):548-8.
26. 26. McDermott DF, Choueiri TK, Motzer RJ, Aren OR, George S, Powles T, et al. CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features. Journal of Clinical Oncology. 2019;37(15_suppl):4513.