cT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted

Guillem, José G.; Díaz-González, J.A.; Minsky, Bruce D.; Valentini, Vincenzo; Jeong, Seung Yong; Rodrı́guez-Bigas, Miguel A.; Coco, Claudio; Leon, Rebecca; Hernández-Lizoain, José Luís; Aristu, Javier; Riedel, Elyn; Nitti, Donato; Wong, W. Douglas; Pucciarelli, Salvatore

doi:10.1200/jco.2007.13.5434

Cited by 213 publications

(121 citation statements)

References 39 publications

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“…5,15 However, for pathological-staged T3N0 rectal cancer, the value of adjuvant radiotherapy for all patients remains controversial. Park et al did not find a significant difference in LR rate between patients who did and did not receive adjuvant radiotherapy in 390 pT3N0 patients.…”

Section: Discussionmentioning

confidence: 99%

Perineural invasion in pT3N0 rectal cancer

Peng

Sheng

Huang

et al. 2010

Cancer

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BACKGROUND:The authors' purpose was to explore the incidence and prognostic significance of perineural invasion (PNI) in pT3N0 rectal cancer. METHODS: Pathologic materials from resected specimens of 173 patients with pT3N0 rectal cancer were retrospectively collected. PNI-positivity was categorized into 2 groups: surrounding the nerve sheath (SS-PNI) and invading through the nerve sheath (TS-PNI). The rate of PNI-positivity was compared with PNI as initially recorded in the original reports. Patients' outcome was studied in groups with different PNI status, and multivariate analysis was performed to determine its prognostic value. RESULTS: In this retrospective analysis, PNIpositivity was found in 24.3% of all cases, in which SS-PNI and TS-PNI were 11% and 13.3%, respectively, and was related to lymphovascular invasion. Only 7.5% of patients' specimens were reported as PNI-positive in the original reports. Detection of SS-PNI was likelier to be missed than TS-PNI. The rates of local recurrence, disease-free survival, and overall survival at 5 years were similar between the groups of SS-PNI and TS-PNI. The 5-year local recurrence rate was more than 2.5-fold higher in the PNI-positive group compared with the PNI-negative group (22.7% vs 7.9%, respectively; P ¼ .017). Multivariate analysis proved that PNI-positivity was the only independent risk factor for predicting 5-year local recurrence rate, whereas only sampled lymph nodes was related to 5-year disease-free survival and overall survival. CONCLUSIONS: PNI is a common pathologic feature in rectal cancer. The definition of PNI should include SS-PNI and TS-PNI. Rectal cancer patients who are PNI-positive are at higher risk of local recurrence and should be considered for more intensive treatment.

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Section: Discussionmentioning

confidence: 99%

Perineural invasion in pT3N0 rectal cancer

Peng

Sheng

Huang

et al. 2010

Cancer

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“…Biological markers predictive of poor clinical outcome from the preoperative biopsy would be useful tools to complement clinical staging. To date, such biological markers have had limited impact, including both the molecular analysis of K-ras and p53, as well as immunohistochemical markers (Turner et al, 2007;Guillem et al, 2008). There is currently no tissue-based marker, which is recommended as a prognostic factor by the European Group on Tumour Markers for patients with rectal cancer (Duffy et al, 2007).…”

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confidence: 99%

Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

et al. 2008

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The aim of this study was to establish an immunohistochemical protein profile to complement preoperative staging and identify rectal cancer patients at high-risk of adverse outcome. Immunohistochemistry was performed on a tissue microarray including 482 rectal cancers for APAF-1, EphB2, MST1, Ki67, p53, RHAMM, RKIP and CD8 þ tumour infiltrating lymphocytes (TILs). After resampling of the data and multivariable analysis, the most reproducible markers were combined and prognosis evaluated as stratified by pT and pN status. In multivariable analysis, only positive RHAMM (Po0.001; HR ¼ 1.94 (1.44 -2.61)) and loss of CD8 þ TILs (P ¼ 0.006; HR ¼ 0.63 (0.45 -0.88)) were independent prognostic factors. The 5-year cancer-specific survival rate for RHAMM þ /TILÀ patients was 30% (95% CI 21 -40%) compared to 76% (95% CI: 66 -84%) for RHAMMÀ/TIL þ patients (Po0.001). The 5-year cancerspecific survival of T1/T2/RHAMM þ /TILÀ patients was 48% (20 -72%) and significantly worse compared to T3/T4/RHAMMÀ/ TIL þ patients (71% 95% CI 56 -82%); P ¼ 0.039). Stratifying by nodal status, only N þ /RHAMM þ /TILÀ patients demonstrated a significantly worse prognosis than N0/RHAMM þ /TILÀ patients (P ¼ 0.005). Loss of CD8 þ TILs was predictive of local recurrence in RHAMM þ tumours (P ¼ 0.009) only. RHAMM and CD8 þ TILs may assist in identifying early stage rectal cancer patients facing a particularly poor prognosis and who may derive a benefit from preoperative therapy.

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“…With the current staging methods an overtreatment is performed in probably 18% of the patients, most of them wrongly staged as cT3N0 (2). However, this overtreatment is intentional as 22% of the pT3 tumours had a previously undetected involvement of mesorectal lymph nodes and would have poorer local control with postoperative treatment (46). This means that at present the incidence of side effects in overtreated patients who would require nothing other than surgery unfortunately has to be accepted to include most of the patients to neoadjuvant treatment who really need it.…”

Section: Discussionmentioning

confidence: 99%