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

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

Öz

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.

Anahtar Kelimeler

• Rectal cancer
• perinöral invazyon
• sağkalım

Kaynakça

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