Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation

Bensignor, Thierry; Brouquet, Antoine; Dariane, C.; Lazure, Thierry; Julié, Catherine; Nordlinger, Bernard; Penna, Christophe; Benoist, Stéphane

doi:10.1111/codi.12879

Cited by 19 publications

(12 citation statements)

References 30 publications

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“…'Systemic therapy alone' can also induce significant response of the tumour. A case series of 22 patients with rectal cancer demonstrated an objective pathological response in 12 patients, including one patient with a complete response [68]. Prior to the start of treatment, symptomatic rectal tumours with clinical signs of obstruction should be decompressed with a colostomy to avoid treatment delays for emergency intervention.…”

Section: Rectal Cancer With Synchronous Liver Metastasesmentioning

confidence: 99%

Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer

Lutz

Zalcberg

Glynne‐Jones

et al. 2016

European Journal of Cancer

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Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.

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Section: Rectal Cancer With Synchronous Liver Metastasesmentioning

confidence: 99%

Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer

Lutz

Zalcberg

Glynne‐Jones

et al. 2016

European Journal of Cancer

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“…Indeed, in these settings, discussions of neoadjuvant treatment in patients contra‐indicated for CRT appear to be mainly focused on the administration of neoadjuvant chemotherapy alone . However, the role of chemotherapy as the sole modality in RC neoadjuvant treatment is not yet well established .…”

Section: Discussionmentioning

confidence: 99%

Previous radiation for prostate neoplasm alters surgical and oncologic outcomes after rectal cancer surgery

Guandalino¹,

Dupré²,

François³

et al. 2015

Journal of Surgical Oncology

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“…Recent phase II and one phase III studies evaluated the feasibility and the safety of preoperative oxaliplatinbased chemotherapy without pelvic irradiation prior to total mesorectal excision in selected patients with cT2-T3Nx rectal cancer [13][14][15]27]. These studies have shown that preoperative chemotherapy alone was associated with a high rate of complete R0 resection (100%), a low risk of postoperative local recurrence (0-2%) and progression free-survival up to 92% at 4-year in selected LARC patients.…”

Section: The Choice Of Modified Folfirinox As Preoperative Treatment For Locally Advanced Rectal Cancermentioning

confidence: 99%

“…Finally, consistent data have shown that preoperative pelvic irradiation is associated with a higher risk of long term digestive and genitourinary dysfunction compared to patients undergoing surgery alone [11,12]. A number of recent studies suggest that preoperative full-dose oxaliplatin-based chemotherapy could be efficient for local control and used as an alternative to RCT in selected LARC patients [13][14][15]. This approach could have the advantage to limit the risk of local recurrence after surgery by analogy to RCT but without the risk of late side effects associated with pelvic irradiation.…”

Section: Introductionmentioning

confidence: 99%

NORAD01-GRECCAR16 multicenter phase III non-inferiority randomized trial comparing preoperative modified FOLFIRINOX without irradiation to radiochemotherapy for resectable locally advanced rectal cancer (intergroup FRENCH-GRECCAR- PRODIGE trial)

et al. 2020

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Background Preoperative radiochemotherapy (RCT) is recommended in France prior to total mesorectal excision in patients with mid or low locally advanced rectal cancer (LARC) (cT3/T4 and/or N+) because it has been shown to improve local control. Preoperative RCT has also disadvantages including the absence of proven impact on metastatic recurrence and the risk of late side effects on bowel and genitourinary function. In patients with primarily resectable LARC, preoperative systemic chemotherapy without pelvic irradiation could be used as an alternative to RCT. Methods This study is a multicenter, open-label randomized, 2-arm phase III non-inferiority trial. Patients with mid or low resectable LARC (cT3N0 or cT1-T3N+ with circumferential resection margin [CRM] > 2 mm on pretreatment MRI) will be randomized to either modified FOLFIRINOX for 3 months or RCT (Cap50 intensified-modulated radiotherapy). All patients have restaging MRI after preoperative treatment. The primary endpoint is 3-year progression-free survival (PFS) from the time to randomization including progression during preoperative treatment. Secondary endpoints are treatment related toxicity, treatment compliance, R0 resection rate, sphincter saving surgery rate, postoperative morbidity and mortality rates, loco-regional recurrence free survival, overall survival, bowel and sexual functions at diagnosis, quality of life, radiologic and pathologic response after preoperative treatment. The number of patients required is 574. Discussion The choice of modified FOLFIRINOX for preoperative chemotherapy is supported by recent and consistent data on safety and efficacy of this regimen on rectal cancer. The use of preoperative chemotherapy instead of RCT could be associated with pronounced advantages in terms of functional results and quality of life in cancer survivors. However and first of all, the non-inferiority of preoperative chemotherapy compared to RCT on oncologic outcome has to be validated. If this study demonstrates the non-inferiority of chemotherapy compared to RCT, this can lead to a crucial change in clinical practice in a large subset of rectal cancer patients. Trial registration ClinicalTrials.gov NCT03875781 (March 15, 2019). Version 1.1.

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Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation

Cited by 19 publications

References 30 publications

Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer

Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer

Previous radiation for prostate neoplasm alters surgical and oncologic outcomes after rectal cancer surgery

NORAD01-GRECCAR16 multicenter phase III non-inferiority randomized trial comparing preoperative modified FOLFIRINOX without irradiation to radiochemotherapy for resectable locally advanced rectal cancer (intergroup FRENCH-GRECCAR- PRODIGE trial)

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