Predictors of Pathologic Response After Total Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: A National Cancer Database Analysis

McDermott, D.; Singh, Sarah A.; Renz, Paul; Hasan, Shaakir; Weir, Josh

doi:10.7759/cureus.17233

Cited by 3 publications

(5 citation statements)

References 18 publications

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“…A systematic review further supported these findings, reporting pooled pCR rates of 32.4% for TNT and 22.3% for CRT, underscoring the benefits of the total neoadjuvant therapy approach (15). Moreover, in our patients the requirement for a permanent stoma was notably lower in the TNT group compared to the CRT group (21.7% vs. 31.7%), although this difference approached but did not reach statistical significance (P = .076).…”

Section: Discussionsupporting

confidence: 67%

Comparing real-world outcomes of total neoadjuvant treatment and CRT at a tertiary medical center

Turfa,

Alawabdeh,

Naser

et al. 2023

Front. Oncol.

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IntroductionFor years, standard treatment for locally advanced rectal cancer (LARC) has included neoadjuvant chemoradiotherapy (CRT), followed by surgery and adjuvant chemotherapy. Although CRT has helped reduce local recurrence rates, it hasn’t consistently improved overall survival. Recent trials have unveiled a different approach called total neoadjuvant treatment (TNT), involving pre-surgery radiotherapy followed by chemotherapy (CAPOX/FOLFOX). TNT shows promise with improved treatment response and lower distant metastasis rates without compromising local control. Consequently, many healthcare institutions have adopted TNT as their preferred neoadjuvant treatment. This study, conducted at a tertiary center, compares the real-world outcomes of both CRT and TNT protocols.MethodsIn this retrospective study of 390 patients treated between 2015 and 2021, aged 18 or older with LARC and tumors within 12 cm of the anal verge, we compared treatment outcomes. We assessed factors like pathological complete remission (pCR), three-year event-free survival (EFS), and overall survival (OS) between the two treatment groups using the Chi-squared test.ResultsOut of the 390 eligible patients, 256 underwent CRT, while 84 received TNT. Surgery was performed on 215 (84%) patients in the CRT group, compared to 55 (65.5%) in the TNT group. Notably, 33 (12.8%) achieved pCR in the CRT group, whereas 23 (27.7%) achieved pCR in the TNT group (P <.001). Regardless of whether surgery was performed or not, the TNT group exhibited lower recurrence rates (12.7% vs. 18.6% with surgery, 28.6% vs. 45% without surgery). The 3-year EFS rate was 80% in the CRT group and 90% in the TNT group (P = .05). Additionally, the 3-year OS rates favored the TNT group, standing at 96.4% compared to 84.4% in the CRT group (P = .005).ConclusionOur findings indicate that patients who underwent TNT demonstrated a higher likelihood of achieving pCR and experienced lower recurrence rates compared to those in the CRT group. Additionally, the TNT group exhibited superior 3-year EFS and OS. It is important to note, however, that a longer follow-up period is required to further validate these results.

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Section: Discussionsupporting

confidence: 67%

Comparing real-world outcomes of total neoadjuvant treatment and CRT at a tertiary medical center

Turfa,

Alawabdeh,

Naser

et al. 2023

Front. Oncol.

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Section: The Benefit Of Tnt Based On Clinical Predictorsmentioning

confidence: 99%

“…A study from the United States analyzed patient and treatment characteristics associated with pCR for 350 patients in the National Cancer Database that underwent TNT [34]. When stratified by clinical stage, patients with cT4 disease were associated with worse pCR rates and those with cT3 or cN1 disease had improved overall survival [34]. Additionally, patients who underwent TNT had statistically significant improvement in nodal response (ypT + N0) compared to those undergoing neoadjuvant CRT, further leading to improved overall survival for patients with advanced stage cancer [34].…”

Section: The Benefit Of Tnt Based On Clinical Predictorsmentioning

confidence: 99%

“…Two studies found advanced cancer staging, specifically cN2 and cT4, to be negatively associated with pCR after TNT. While the McDermott paper is limited by uncertainties in the accuracy of the database as well as a lack of other prognostic information not recorded [34], this sentiment is supported by the positive tumor response after TNT in early rectal cancer as examined by Habr-Gama [47]. While excluded from our analysis due to clinical stage as well as limitations in the implications and generalizability of this study, they examined the effects of extended CRT with consolidation chemotherapy, or tailored TNT, on patients with cT2N0.…”

Section: Clinical Predictorsmentioning

confidence: 99%

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The Predictors of Complete Pathologic Response in Rectal Cancer during the Total Neoadjuvant Therapy Era: A Systematic Review

Flom,

Schultz,

Pantel

et al. 2023

Cancers

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The modern rectal cancer treatment paradigm offers additional opportunities for organ preservation, most notably via total neoadjuvant therapy (TNT) and consideration for a watch-and-wait (WW) surveillance-only approach. A major barrier to widespread implementation of a WW approach to rectal cancer is the potential discordance between a clinical complete response (cCR) and a pathologic complete response (pCR). In the pre-TNT era, the identification of predictors of pCR after neoadjuvant therapy had been previously studied. However, the last meta-analysis to assess the summative evidence on this important treatment decision point predates the acceptance and dissemination of TNT strategies. The purpose of this systematic review was to assess preoperative predictors of pCR after TNT to guide the ideal selection criteria for WW in the current era. An exhaustive literature review was performed and the electronic databases Embase, Ovid, MEDLINE, PubMed, and Cochrane were comprehensively searched up to 27 June 2023. Search terms and their combinations included “rectal neoplasms”, “total neoadjuvant therapy”, and “pathologic complete response”. Only studies in English were included. Randomized clinical trials or prospective/retrospective cohort studies of patients with clinical stage 2 or 3 rectal adenocarcinoma who underwent at least 8 weeks of neoadjuvant chemotherapy in addition to chemoradiotherapy with pCR as a measured study outcome were included. In this systematic review, nine studies were reviewed for characteristics positively or negatively associated with pCR or tumor response after TNT. The results were qualitatively grouped into four categories: (1) biochemical factors; (2) clinical factors; (3) patient demographics; and (4) treatment sequence for TNT. The heterogeneity of studies precluded meta-analysis. The level of evidence was low to very low. There is minimal data to support any clinicopathologic factors that either have a negative or positive relationship to pCR and tumor response after TNT. Additional data from long-term trials using TNT is critical to better inform those considering WW approaches following a cCR.

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“…The achievement of a complete remission provides the possibility for organ-preserving surgery or a non-operative, watch-and-wait (W&W) approach. Research efforts have been directed toward identification of clinical and other parameters that could help predict pCR after preoperative treatment [ 14 , 15 , 16 , 17 , 18 , 19 ]. However, several unclear issues, particularly related to the importance of clinical T-stage (cT-stage), tumour length, presence of extramural vascular invasion (cEMVI+), mesorectal fascia (cMRF+) involvement, and clinical laboratory values need to be clarified [ 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters

Karimi

Österlund

Hammarström

et al. 2022

Cancers

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Complete pathological response (pCR) is achieved in 10–20% of rectal cancers when treated with short-course radiotherapy (scRT) or long-course chemoradiotherapy (CRT) and in 28% with total neoadjuvant therapy (scRT/CRT + CTX). pCR is associated with better outcomes and a “watch-and-wait” strategy (W&W). The aim of this study was to identify baseline clinical or imaging factors predicting pCR. All patients with preoperative treatment and delays to surgery in Uppsala-Dalarna (n = 359) and Stockholm (n = 635) were included. Comparison of pCR versus non-pCR was performed with binary logistic regression models. Receiver operating characteristics (ROC) models for predicting pCR were built using factors with p < 0.10 in multivariate analyses. A pCR was achieved in 12% of the 994 patients (scRT 8% [33/435], CRT 13% [48/358], scRT/CRT + CTX 21% [43/201]). In univariate and multivariate analyses, choice of CRT (OR 2.62; 95%CI 1.34–5.14, scRT reference) or scRT/CRT + CTX (4.70; 2.23–9.93), cT1–2 (3.37; 1.30–8.78; cT4 reference), tumour length ≤ 3.5 cm (2.27; 1.24–4.18), and CEA ≤ 5 µg/L (1.73; 1.04–2.90) demonstrated significant associations with achievement of pCR. Age < 70 years, time from radiotherapy to surgery > 11 weeks, leucocytes ≤ 109/L, and thrombocytes ≤ 4009/L were significant only in univariate analyses. The associations were not fundamentally different between treatments. A model including T-stage, tumour length, CEA, and leucocytes (with scores of 0, 0.5, or 1 for each factor, maximum 4 points) showed an area under the curve (AUC) of 0.66 (95%CI 0.60–0.71) for all patients, and 0.65–0.73 for the three treatments separately. The choice of neoadjuvant treatment in combination with low CEA, short tumour length, low cT-stage, and normal leucocytes provide support in predicting pCR and, thus, could offer guidance for selecting patients for organ preservation.

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Predictors of Pathologic Response After Total Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: A National Cancer Database Analysis

Cited by 3 publications

References 18 publications

Comparing real-world outcomes of total neoadjuvant treatment and CRT at a tertiary medical center

Comparing real-world outcomes of total neoadjuvant treatment and CRT at a tertiary medical center

The Predictors of Complete Pathologic Response in Rectal Cancer during the Total Neoadjuvant Therapy Era: A Systematic Review

Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters

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