The Importance of Being “That” Colorectal pT1: A Combined Clinico-Pathological Predictive Score to Improve Nodal Risk Stratification

Gambella, Alessandro; Falco, Enrico Costantino; Benazzo, Giacomo Maria; Osella‐Abate, Simona; Senetta, Rebecca; Castellano, Isabella; Bertero, Luca; Cassoni, Paola

doi:10.3389/fmed.2022.837876

Cited by 6 publications

(6 citation statements)

References 67 publications

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“…Additionally, we reported a worse RFS in stage I EORC patients when compared to the LORC counterpart [ 12 ]. Age > 65 years was identified as an independent factor associated with a lower risk for nodal metastases in T1 CRC in two recently published studies [ 15 , 16 ]. Although the cut-off age does not correspond to EOCRC, this result indicates that in early-stage CRC there is an oncological risk related to a younger age, which should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients

Foppa

Maroli

Lauricella

et al. 2022

Cancers

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The incidence of colorectal cancer (CRC) is increasing in the population aged ≤ 49 (early-onset CRC-EOCRC). Recent studies highlighted the biological and clinical differences between EOCRC and late-onset CRC (LOCRC-age ≥ 50), while comparative results about long-term survival are still debated. This study aimed to investigate whether age of onset may impact on oncologic outcomes in a surgical population of sporadic CRC patients. Patients operated on for sporadic CRC from January 2010 to January 2022 were allocated to the EOCRC and LOCRC groups. The primary endpoint was the recurrence/progression-free survival (R/PFS). A total of 423 EOCRC and 1650 LOCRC was included. EOCRC had a worse R/PFS (p < 0.0001) and cancer specific survival (p < 0.0001) compared with LOCRC. At Cox regression analysis, age of onset, tumoral stage, signet ring cells, extramural/lymphovascular/perineural veins invasion, and neoadjuvant therapy were independent risk factors for R/P. The analysis by tumoral stage showed an increased incidence of recurrence in stage I EOCRC (p = 0.014), and early age of onset was an independent predictor for recurrence (p = 0.035). Early age of onset was an independent predictor for worse prognosis, this effect was stronger in stage I patients suggesting a potentially—and still unknown—more aggressive tumoral phenotype in EOCRC.

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Section: Discussionmentioning

confidence: 99%

Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients

Foppa

Maroli

Lauricella

et al. 2022

Cancers

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“…To date, surgical indication after endoscopic removal of a pT1 CRC is based on several histopathological criteria, 6,31 but nodal metastases are ultimately present in 4.9–15.7% of pT1 CRC only 9–14,32 . Similarly, in our series of surgically resected specimens only a minority of patients (19 of 81; 23.4%) had nodal metastasis, suggesting a large degree of overtreatment.…”

Section: Discussionmentioning

confidence: 58%

“…By adopting the proposed PD‐L1 CPS and ICS cut‐offs, all patients with nodal metastases within our series would have received surgical indication, and more than 40% of unnecessary surgeries (pN0 patients) would have been avoided. If we compare these results with the high rate (even more than 85%) of merely stadiative surgeries observed using the current criteria, 9–14,32 it is evident how evaluation of this marker could help to achieve a significant improvement.…”

Section: Discussionmentioning

confidence: 94%

“…9 Refining the current risk stratification schemes is critical to avoid the current high rate of unnecessary surgeries, as nodal metastases are ultimately detected in a limited subset (4.9-15.7%) of pT1 CRC only. [9][10][11][12][13][14] In this context, some recent studies have suggested a possible relationship between programmed death ligand 1/CD274 (PD-L1) expression and prognosis in CRCs. [15][16][17][18] Specifically, it has been demonstrated that higher expression of PD-L1 in tumour infiltrating immune cells imparts a better prognosis in different CRC stages, 19 but this association has not been specifically tested in the subset of early invasive lesions.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, the potential benefits of surgery ought to be carefully weighed against its morbidity, mortality and overall socioeconomic costs 9 . Refining the current risk stratification schemes is critical to avoid the current high rate of unnecessary surgeries, as nodal metastases are ultimately detected in a limited subset (4.9–15.7%) of pT1 CRC only 9–14 …”

Section: Introductionmentioning

confidence: 99%

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Low PD‐L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment

et al. 2023

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Low PD-L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment Aims: The current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD-L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal. Methods and results: Histopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non-metastatic cases were assessed. PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and impact upon patients' surgical management were determined. PD-L1 expression in terms of CPS and ICS independently correlated with lymph node metastasis (PD-L1 CPS : OR = -2.5, 95% CI = À4.11 to À0.97, P = 0.008 and PD-L1 ICS : OR = À1.85, 95% CI = À2.90 to À0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non-metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1 CPS = 43.2; PD-L1 ICS = 51.9%). Ultimately, PD-L1 evaluation showed good interpathologist concordance in absolute terms [PD-L1 CPS interclass correlation coefficient (ICC) = 0.91; PD-L1 ICS ICC = 0.793] and using the identified cut-off values (PD-L1 CPS ICC = 0.848; PD-L1 ICS ICC = 0.756). Conclusions: Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.

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Prediction of disease recurrence or residual disease after primary endoscopic resection of pT1 colorectal cancer—results from a large nationwide Danish study

Ose,

Levic,

Thygesen

et al. 2023

Int J Colorectal Dis

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Purpose Risk assessment of disease recurrence in pT1 colorectal cancer is crucial in order to select the appropriate treatment strategy. The study aimed to develop a prediction model, based on histopathological data, for the probability of disease recurrence and residual disease in patients with pT1 colorectal cancer. Methods The model dataset consisted of 558 patients with pT1 CRC who had undergone endoscopic resection only (n = 339) or endoscopic resection followed by subsequent bowel resection (n = 219). Tissue blocks and slides were retrieved from Pathology Departments from all regions in Denmark. All original slides were evaluated by one experienced gastrointestinal pathologist (TPK). New sections were cut and stained for haematoxylin and eosin (HE) and immunohistochemical markers. Missing values were multiple imputed. A logistic regression model with backward elimination was used to construct the prediction model. Results The final prediction model for disease recurrence demonstrated good performance with AUC of 0.75 [95% CI 0.72–0.78], HL chi-squared test of 0.59 and scaled Brier score of 10%. The final prediction model for residual disease demonstrated medium performance with an AUC of 0.68 [0.63–0.72]. Conclusion We developed a prediction model for the probability of disease recurrence in pT1 CRC with good performance and calibration based on histopathological data. Together with lymphatic and venous invasion, an involved resection margin (0 mm) as opposed to a margin of ≤ 1 mm was an independent risk factor for both disease recurrence and residual disease.

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The Importance of Being “That” Colorectal pT1: A Combined Clinico-Pathological Predictive Score to Improve Nodal Risk Stratification

Cited by 6 publications

References 67 publications

Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients

Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients

Low PD‐L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment

Prediction of disease recurrence or residual disease after primary endoscopic resection of pT1 colorectal cancer—results from a large nationwide Danish study

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