Investigation of the effect of perineural invasion on survival rates in rectal tumors

Year 2023, , 304 - 316, 05.04.2023

Utku Ozgen , Uğur Sungurtekin , Neşe Demirkan

https://doi.org/10.31362/patd.1250890

Abstract

Purpose: Colorectal cancers compose the third most common cancer group leading to death, with increasing rates in developed countries after lung and breast cancers. Rectal cancers make up about 30% of all colorectal cancers. Although many factors affecting recurrence and survival in rectal cancer have been identified, the stage of the tumor is the most important prognostic factor. However, many additional parameters that can be associated with survival and affect the adjuvant treatment plan have been identified besides the stage. Perineural invasion (PNI) is one of the parameters that can be associated with survival and affect the adjuvant treatment plan in colorectal cancers. The aim of this study is to investigate the effects of various histopathological prognostic factors, including PNI on disease-free survival, overall survival, and recurrence rates in the study group.
Materials and methods: The clinical records of patients diagnosed with rectal cancer and operated on at the Department of General Surgery, Faculty of Medicine, Pamukkale University between 2008-2014 were reviewed. To investigate the factors affecting disease-free survival, recurrence rates, and overall survival, the presence of PNI, serum CEA levels, cTNM stage, pT stage, pN stage, number of metastatic LNs, tumor budding status, histopathological grades, lymphocyte infiltration, and presence of desmoplasia were evaluated in patients.
Results: A total of 124 patients were included in the study. 42 patients (33.9%) had PNI while 82 patients (66.1%) did not. Of the 45 patients with recurrence, 26 had PNI while 19 did not have PNI. Of the 79 patients without recurrence, 16 had PNI while 63 did not exhibit any evidence of PNI. Similarly, PNI was seen more frequently in deaths related to the disease. The 3-year average survival of patients with and without PNI was 55% and 89%, respectively (p<0.05). The 5-year survival was 38% and 83% respectively (p<0.05). Similarly, there was a significant relationship between the presence of PNI and 3-year disease-free survival (46.8% and 84.1% respectively, p<0.05) and 5-year disease-free survival (22.3% and 80.4% respectively, p<0.05). In the multivariate analysis in which other prognostic factors were also evaluated, the presence of PNI was found to be significantly associated with both overall survival (HR:3.4, 95% CI:1.7-7.2) and disease-free survival (HR:3.0, 95% CI:1.6-5.6).
Conclusion: PNI presence is a strong and independent prognostic indicator for survival. Large-scale, randomized, prospective studies are needed to determine whether PNI presence should be taken into account in the staging of colorectal cancer or play a role in choosing adjuvant therapy.

Keywords

Rectal cancer, perineural invasion, survival

Rektum tümörlerinde perinöral invazyonun sağkalım oranlarına etkisinin araştırılması

Abstract

Amaç: Kolorektal kanserler insidansı gelişmiş ülkelerde giderek artan oranlarda akciğer ve meme kanserlerinden sonra en sık ölüme yol açan üçüncü kanser grubunu oluşturmaktadır. Tüm kolorektal kanserlerin %30 kadarını ise rektum kanserleri oluşturmaktadır. Rektum kanserlerinde nüks gelişimi ve sağkalım üzerine etkisi olabilecek birçok faktör tanımlanmış olmakla birlikte en önemli prognostik faktör tümörün evresidir. Ancak evre ile birlikte sağkalımla ilişkili olabilecek ve adjuvan tedavi planını etkileyebilecek birçok ek parametre tanımlanmıştır. Perinöral invazyon (PNİ) da kolorektal kanserlerde sağkalımla ilişkili olabilecek ve adjuvan tedavi planını etkileyebilecek parametrelerden birisidir. Bu çalışmanın amacı rektum kanseri nedeniyle opere edilen hastaların başta PNİ olmak üzere çeşitli histopatolojik prognostik faktörlerin hastalıksız sağkalıma, genel sağkalıma, rekürrens oranlarına etkilerinin araştırılmasıdır.
Gereç ve yöntem: Pamukkale Üniversitesi Tıp Fakültesi Hastanesi’nde 2008-2014 yılları arasında rektum kanseri tanısı koyularak Genel Cerrahi Anabilim Dalı tarafından opere edilen hastaların klinik kayıtları incelendi. Olgularda hastalıksız sağkalıma, nüks oranlarına ve genel sağkalıma etki eden faktörleri araştırmak amacıyla başta PNİ olmak üzere serum CEA düzeyleri, tümör evresi (cTNM, pT, ve pN evresi), metastatik LN sayıları, tümör budding durumu, tümör gradeleri, lenfosit infiltrasyonu ve desmoplazi varlığı değerlendirilmiştir.
Bulgular: Bu çalışma toplam 124 hasta analiz edilmiştir. Hastaların 42 tanesinde (%33,9) PNİ saptanırken kalan 82 hastada (%66,1) PNİ saptanmadı. Nüks saptanan 45 hastanın 26 tanesinde PNİ saptanırken 19 tanesinde saptanmamıştır. Nüks saptanmayan 79 hastanın 16 tanesinde PNİ varken 63 tanesinde PNİ saptanmamıştır. Benzer şekilde hastalığa bağlı ölümlerde PNİ anlamlı olarak daha sık görülmektedir. PNİ olan ve olmayan hastaların 3 yıllık ortalama sağkalımları sırası ile %55 ve %89 olarak saptandı (p<0,05). 5 yıllık sağkalımları ise sırası ile %38 ve %83 olarak saptandı (p<0,05). Benzer şekilde PNİ varlığı ile 3 yıllık hastalıksız sağkalım (sırası ile %46,8 ve %84,1, p<0,05) ve 5 yıllık hastalıksız sağkalımları (sırası ile %22,3 ve %80,4, p<0,05) arasında anlamlı ilişki bulundu. Diğer prognostik faktörlerin de incelendiği multivariate analizde PNİ varlığı hem genel sağkalım için (HR:3,4; 1,7-6,7; %95CI, p<0,001) hem de hastalıksız sağkalım için (HR:2,5; 1,2-4,9; %95 CI, p<0,001) bağımsız prognostik faktör olarak saptanmıştır.
Sonuç: PNİ varlığının sağkalım için güçlü ve bağımsız bir prognostik belirteç olduğu saptanmıştır. PNİ varlığının kolorektal kanser evrelemesinde dikkate alınması ya da adjuvan tedavi seçiminde rol oynayabilmesi için geniş kapsamlı randomize prospektif olarak dizayn edilmiş çalışmalara ihtiyaç vardır.

Keywords

Rectal cancer, perinöral invazyon, sağkalım

Supporting Institution

yok

References

• 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. https://doi.org/10.3322/caac.21492
• 2. Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, Jemal A. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst 2017;109:322. https://doi.org/10.1093/jnci/djw322
• 3. Haggstrom L, Kang S, Winn R, et al. Factors influencing recurrence of stage I-III rectal cancer in regional Australia. ANZ J Surg 2020;90:2490-2495. https://doi.org/10.1111/ans.16187
• 4. Kim YI, Kim CW, Kim JH, et al. Clinical implication of perineural and lymphovascular invasion in rectal cancer patients who underwent surgery after preoperative chemoradiotherapy. Dis Colon Rectum 2022;65:1325-1334. https://doi.org/10.1097/DCR.0000000000002219
• 5. Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer 2009;115:3379-3391. https://doi.org/10.1002/cncr.24396
• 6. Gong P, Chen C, Wang Z, et al. Prognostic significance for colorectal carcinoid tumors based on the 8th edition TNM staging system. Cancer Med 2020;9:7979-7987. https://doi.org/10.1002/cam4.3431
• 7. Ghazi S, Lindforss U, Lindberg G, Berg E, Lindblom A, Papadogiannakis N. Low-Risk Colorectal Cancer Study Group. Analysis of colorectal cancer morphology in relation to sex, age, location, and family history. J Gastroenterol 2012;47:619-634. https://doi.org/10.1007/s00535-011-0520-9
• 8. Panizza B, Warren T. Perineural invasion of head and neck skin cancer: diagnostic and therapeutic implications. Curr Oncol Rep 2013;15:128-133. https://doi.org/10.1007/s11912-012-0288-y
• 9. Harnden P, Shelley MD, Clements H, Coles B, Tyndale Biscoe RS, Naylor B, Mason MD. The prognostic significance of perineural invasion in prostatic cancer biopsies: a systematic review. Cancer 2007;109:13-24. https://doi.org/10.1002/cncr.22388
• 10. Li J, Kang R, Tang D. Cellular and molecular mechanisms of perineural invasion of pancreatic ductal adenocarcinoma. Cancer Commun (Lond). 2021;41:642-660. https://doi.org/10.1002/cac2.12188
• 11. Yang Y, Huang X, Sun J, et al. Prognostic value of perineural invasion in colorectal cancer: a meta-analysis. J Gastrointest Surg 2015;19:1113-1122. https://doi.org/10.1007/s11605-015-2761-z
• 12. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-1474. https://doi.org/10.1245/s10434-010-0985-4
• 13. Huh JW, Lee JH, Kim HR, Kim YJ. Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer. Am J Surg 2013;206:758-763. https://doi.org/10.1016/j.amjsurg.2013.02.010
• 14. Batsakis JG. Nerves and neurotropic carcinomas. Ann Otol Rhinol Laryngol 1985;94:426-427.
• 15. Seefeld PH, Bargen JA. The spread of carcinoma of the rectum: invasion of lymphatics, veins and nerves. Ann Surg 1943;118:76-90. https://doi.org/10.1097/00000658-194311810-00005
• 16. Tsai HL, Cheng KI, Lu CY, et al. Prognostic significance of depth of invasion, vascular invasion and numbers of lymph node retrievals in combination for patients with stage II colorectal cancer undergoing radical resection. J Surg Oncol 2008;97:383-387. https://doi.org/10.1002/jso.20942
• 17. Fujita S, Shimoda T, Yoshimura K, Yamamoto S, Akasu T, Moriya Y. Prospective evaluation of prognostic factors in patients with colorectal cancer undergoing curative resection. J Surg Oncol 2003;84:127-131. https://doi.org/10.1002/jso.10308
• 18. Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T. Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors. Mod Pathol 2003;16:293-298. https://doi.org/10.1097/01.MP.0000062654.83617.B7
• 19. Ueno H, Shirouzu K, Eishi Y, et al. Study Group for Perineural Invasion projected by the Japanese Society for Cancer of the Colon and Rectum (JSCCR). Characterization of perineural invasion as a component of colorectal cancer staging. Am J Surg Pathol 2013;37:1542-1549. https://doi.org/10.1097/PAS.0b013e318297ef6e
• 20. Chen K, Collins G, Wang H, Toh JWT. Pathological features and prognostication in colorectal cancer. Curr Oncol 2021;28:5356-5383. https://doi.org/10.3390/curroncol28060447
• 21. Knijn N, Mogk SC, Teerenstra S, Simmer F, Nagtegaal ID. Perineural invasion is a strong prognostic factor in colorectal cancer: a systematic review. Am J Surg Pathol 2016;40:103-112. https://doi.org/10.1097/PAS.0000000000000518
• 22. Cao Y, Deng S, Yan L, et al. Perineural invasion is associated with poor prognosis of colorectal cancer: a retrospective cohort study. Int J Colorectal Dis 2020;35:1067-1075. https://doi.org/10.1007/s00384-020-03566-2
• 23. Şermet M, Celayir F, Baykan A. Küratif rezeksiyon yapılan rektum kanseri olgularında ameliyat sonrası sağkalıma etki eden prognostik faktörlerin analizi. The Medical Bulletin of Şişli Etfal Hospital 2013;47:138-146.
• 24. Ueno H, Shirouzu K, Shimazaki H, et al. Study Group for Perineural Invasion projected by the Japanese Society for Cancer of the Colon and Rectum (JSCCR). Histogenesis and prognostic value of myenteric spread in colorectal cancer: a Japanese multi-institutional study. J Gastroenterol 2014;49:400-407. https://doi.org/10.1007/s00535-013-0822-1
• 25. Huh JW, Kim HR, Kim YJ. Lymphovascular or perineural invasion may predict lymph node metastasis in patients with T1 and T2 colorectal cancer. J Gastrointest Surg 2010;14:1074-1080. https://doi.org/10.1007/s11605-010-1206-y