Подходы к лечению олигометастатической меланомы в эпоху иммунотаргетной терапии

Олигометастатическое заболевание – термин, который описывает состояние опухоли между локализованным образованием и диссеминированным процессом, когда все обнаруженные опухолевые очаги доступны локальному воздействию. Концепция олигометастатической болезни при распространенной меланоме кожи существует с 1970–1980-х гг., и роль метастазэктомии солитарных очагов прочно заняла свою нишу в стратегии лечения данного заболевания. Однако роль локальных методов до внедрения современной системной терапии была довольно скромной в силу агрессивного и часто первично диссеминированного течения заболевания. Внедрение иммунотерапии и современной таргетной терапии в лечение метастатической меланомы позволило существенно увеличить количество пациентов, подходящих под критерии олигометастатического заболевания с возможностью выполнения метастазэктомии. В настоящее время не разработано четкого алгоритма и определенной последовательности комбинации системных методов лечения с хирургическими и другими локальными методами. Сейчас активно обсуждается проведение условно-неоадъювантной иммунотерапии даже при первично операбельных метастазах меланомы. Данная концепция основывается на более высокой эффективности иммунотерапии при наличии опухолевой ткани в организме и уже имеет практическое подтверждение в виде позитивных данных последних исследований. В определении тактики при олигометастатической меланоме крайне важен мультидисципланарный подход, включающий взвешенную оценку возможных локальных хирургических возможностей, применение радиотерапии и обязательный системный контроль заболевания. Успешно применяя и комбинируя данные подходы, у значимой части пациентов возможно добиться выдающихся успехов в контроле заболевания. В данном обзоре проведен анализ основных и наиболее важных работ в мировой литературе по системному и хирургическому лечению олигометастатической меланомы.

1. Dickson PV, Gershenwald JE. Staging and prognosis of cutaneous melanoma. Surg Oncol Clin N Am. 2011;20(1):1–17. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221385/.

2. Hersh EM, Del Vecchio M, Brown MP, Kefford R, Loquai C, Testori A et al. A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. Ann Oncol. 2015;26(11):2267–2274. https://doi.org/10.1093/annonc/mdv324.

3. Fateeva A, Eddy K, Chen S. Current State of Melanoma Therapy and Next Steps: Battling Therapeutic Resistance. Cancers (Basel). 2024;16(8):1571. https://doi.org/10.3390/cancers16081571.

4. Boutros A, Croce E, Ferrari M, Gili R, Massaro G, Marconcini R et al. The treatment of advanced melanoma: Current approaches and new challenges. Crit Rev Oncol Hematol. 2024;196:104276. https://doi.org/10.1016/j.critrevonc.2024.104276.

5. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol. 2022;40(2):127–137. https://doi.org/10.1200/JCO.21.02229.

6. Urbanski A, Minnemann J, Mauch C, Schmidt T, Kreuzberg N, Schlaak M et al. Oligometastatic disease and visceral resections in advanced malignant melanoma: a propensity-matched analysis. Langenbecks Arch Surg. 2023;408(1):53. https://doi.org/10.1007/s00423-023-02804-9.

7. McLoughlin JM, Zager JS, Sondak VK. Cytoreductive surgery for melanoma. Surg Oncol Clin N Am. 2007;16(3):683–693. https://doi.org/10.1016/j.soc.2007.04.007.

8. Enomoto LM, Levine EA, Shen P, Votanopoulos KI. Role of Surgery for Metastatic Melanoma. Surg Clin North Am. 2020;100(1):127–139. https://doi.org/10.1016/j.suc.2019.09.011.

9. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13(1):8–10. https://doi.org/10.1200/JCO.1995.13.1.8.

10. Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I et al. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother Oncol. 2020;148:157–166. https://doi.org/10.1016/j.radonc.2020.04.003.

11. Guckenberger M, Lievens Y, Bouma AB, Collette L, Dekker A, deSouza NM et al. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020;21(1):e18–e28. https://doi.org/10.1016/S1470-2045(19)30718-1.

12. Miller ED, Hitchcock KE, Romesser PB. Oligometastatic Colorectal Cancer: A Review of Definitions and Patient Selection for Local Therapies. J Gastrointest Cancer. 2023;54(4):1116–1127. https://doi.org/10.1007/s12029-022-00900-5.

13. Kroese TE, van Laarhoven HWM, Nilsson M, Lordick F, Guckenberger M, Ruurda JP et al. Definition of oligometastatic esophagogastric cancer and impact of local oligometastasis-directed treatment: A systematic review and meta-analysis. Eur J Cancer. 2022;166:254–269. https://doi.org/10.1016/j.ejca.2022.02.018.

14. Jasper K, Stiles B, McDonald F, Palma DA. Practical Management of Oligometastatic Non-Small-Cell Lung Cancer. J Clin Oncol. 2022;40(6):635–641. https://doi.org/10.1200/JCO.21.01719.

15. Rogowski P, Roach M 3rd, Schmidt-Hegemann NS, Trapp C, von Bestenbostel R, Shi R et al. Radiotherapy of oligometastatic prostate cancer: a systematic review. Radiat Oncol. 2021;16(1):50. https://doi.org/10.1186/s13014-021-01776-8.

16. Michielin O, van Akkooi ACJ, Ascierto PA, Dummer R, Keilholz U. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1884–1901. https://doi.org/10.1093/annonc/mdz411.

17. Seth R, Agarwala SS, Messersmith H, Alluri KC, Ascierto PA, Atkins MB et al. Systemic Therapy for Melanoma: ASCO Guideline Update. J Clin Oncol. 2023;41(30):4794–4820. https://doi.org/10.1200/JCO.23.01136.

18. Versluis JM, Hendriks AM, Weppler AM, Brown LJ, de Joode K, Suijkerbuijk KPM et al. The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis. Eur J Cancer. 2021;151:72–83. https://doi.org/10.1016/j.ejca.2021.04.003.

19. Petersen RP, Hanish SI, Haney JC, Miller CC 3rd, Burfeind WR Jr, Tyler DS et al. Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma. J Thorac Cardiovasc Surg. 2007;133(1):104–110. https://doi.org/10.1016/j.jtcvs.2006.08.065.

20. Sosman JA, Moon J, Tuthill RJ, Warneke JA, Vetto JT, Redman BG et al. A phase 2 trial of complete resection for stage IV melanoma: results of Southwest Oncology Group Clinical Trial S9430. Cancer. 2011;117(20):4740–4706. https://doi.org/10.1002/cncr.26111.

21. Howard JH, Thompson JF, Mozzillo N, Nieweg OE, Hoekstra HJ, Roses DF et al. Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I). Ann Surg Oncol. 2012;19(8):2547–2555. https://doi.org/10.1245/s10434-012-2398-z.

22. O’Neill CH, McMasters KM, Egger ME. Role of Surgery in Stage IV Melanoma. Surg Oncol Clin N Am. 2020;29(3):485–495. https://doi.org/10.1016/j.soc.2020.02.010.

23. Bello DM. Indications for the surgical resection of stage IV disease. J Surg Oncol. 2019;119(2):249–261. https://doi.org/10.1002/jso.25326.

24. Wollina U, Brzezinski P. The value of metastasectomy in stage IV cutaneous melanoma. Wien Med Wochenschr. 2019;169(13-14):331–338. https://doi.org/10.1007/s10354-018-0630-6.

25. Bello DM, Panageas KS, Hollmann T, Shoushtari AN, Momtaz P, Chapman PB et al. Survival Outcomes After Metastasectomy in Melanoma Patients Categorized by Response to Checkpoint Blockade. Ann Surg Oncol. 2020;27(4):1180–1188. https://doi.org/10.1245/s10434-019-08099-9.

26. Orlova KV, Ledin E, Zhukova NV, Orlova R, Protsenko S, Novik A et al. The role of surgery (metastasectomy) in advanced BRAF positive melanoma during modern therapy. J Clin Oncol. 2022;40(Suppl. 16):e21512. https://doi.org/10.1200/JCO.2022.40.16_suppl.e21512.

27. Meacci E, Nachira D, Congedo MT, Ibrahim M, Pariscenti G, Petrella F et al. Surgical Resection of Pulmonary Metastases from Melanoma in Oligometastatic Patients: Results from a Multicentric Study in the Era of Immunoncology and Targeted Therapy. Cancers (Basel). 2023;15(9):2462. https://doi.org/10.3390/cancers15092462.

28. Ch’ng S, Uyulmaz S, Carlino MS, Pennington TE, Shannon KF, Rtshiladze M et al. Re-defining the role of surgery in the management of patients with oligometastatic stage IV melanoma in the era of effective systemic therapies. Eur J Cancer. 2021;153:8–15. https://doi.org/10.1016/j.ejca.2021.04.037.

29. Patel SP, Othus M, Chen Y, Wright GP Jr, Yost KJ, Hyngstrom JR et al. Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma. N Engl J Med. 2023;388(9):813–823. https://doi.org/10.1056/NEJMoa2211437.

30. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–571. https://doi.org/10.1038/nature13954.

31. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887–3895. https://doi.org/10.1002/j.1460-2075.1992.tb05481.x.

32. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19(7):813–824. https://doi.org/10.1093/intimm/dxm057.

33. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99(19):12293–12297. https://doi.org/10.1073/pnas.192461099.

34. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56–61. https://doi.org/10.1126/science.aaa8172.

35. Liu J, Blake SJ, Yong MC, Harjunpää H, Ngiow SF, Takeda K et al. Improved Efficacy of Neoadjuvant Compared to Adjuvant Immunotherapy to Eradicate Metastatic Disease. Cancer Discov. 2016;6(12):1382–1399. https://doi.org/10.1158/2159-8290.CD-16-0577.

36. Blank CU, Rozeman EA, Fanchi LF, Sikorska K, van de Wiel B, Kvistborg P et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24(11):1655–1661. https://doi.org/10.1038/s41591-018-0198-0.

37. Mangla A, Lee C, Mirsky MM, Wang M, Rothermel LD, Hoehn R et al. Neoadjuvant Dual Checkpoint Inhibitors vs Anti-PD1 Therapy in High-Risk Resectable Melanoma: A Pooled Analysis. JAMA Oncol. 2024;10(5):612–620. https://doi.org/10.1001/jamaoncol.2023.7333.

38. Atkins MB, Lee SJ, Chmielowski B, Tarhini AA, Cohen GI, Truong TG et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186–197. https://doi.org/10.1200/JCO.22.01763.

39. Ascierto PA, Mandalà M, Ferrucci PF, Guidoboni M, Rutkowski P, Ferraresi V et al. Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial. J Clin Oncol. 2023;41(2):212–221. https://doi.org/10.1200/JCO.21.02961.

40. Amaria RN, Prieto PA, Tetzlaff MT, Reuben A, Andrews MC, Ross MI et al. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 2018;19(2):181–193. https://doi.org/10.1016/S1470-2045(18)30015-9.

41. Menzies AM, Saw RPM, Lo SN, Gonzalez M, Ch’ng S, Nieweg OE et al. Neoadjuvant dabrafenib and trametinib (D+T) for stage III melanoma: Longterm results from the NeoCombi trial. J Clin Oncol. 2022;40(Suppl. 16):9580. https://doi.org/10.1200/JCO.2022.40.16_suppl.9580.