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Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms.

ABSTRACT: Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy (CRT) followed by total mesorectal excision (TME) reaches a plateau, the need for alternative strategies in locally advanced rectal cancer (LARC) has grown in relevance. Several novel strategies have been conceptualized to address this issue, including: 1) neoadjuvant induction and consolidation chemotherapy before CRT; 2) neoadjuvant chemotherapy alone to avoid the sequelae of radiation; and 3) nonoperative management for patients who achieved pathological or clinical complete response after CRT. This article explores the issues, recent advances and paradigm shifts in the management of LARC and emphasizes the need for a personalized treatment plan for each patient based on tumor stage, location, gene expression and quality of life.

SUBMITTER: Nacion AJD

PROVIDER: S-EPMC5842228 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms.

Nacion Aeris Jane D AJD Park Youn Young YY Kim Nam Kyu NK

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20180201 1

Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy (CRT) followed by total mesorectal excision (TME) reaches a plateau, the need for alternative strategies in locally advanced rectal cancer (LARC) has grown in relevance. Several novel strategies have been conceptualized to address this iss ...[more]

PMID: 29545727

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Project description:The presence of lateral pelvic lymph nodes (LPLN) in advanced rectal cancer entails challenges with ongoing debate regarding the role of prophylactic dissection vs. neoadjuvant radiation treatment. This article highlights the most recent data of both approaches: bilateral LPLN dissection in every patient with low rectal cancer (Rb) as per the Japanese guidelines, vs. the developing approach of neoadjuvant radiotherapy as per Eastern countries. In addition, we also accentuate the importance of a combined approach published by Sammour et al. where a simple "one-size-fits-all" strategy should be abandoned. Rectal cancer treatment is well-established in Western countries. Patients with advanced rectal cancer will undergo radiation ± chemo neoadjuvant therapy followed by TME. In the Dutch TME trial, TME plus radiotherapy showed that the presacral area was the most frequent site of recurrence and not the lateral pelvic wall. Supporting this data, the Swedish study also concluded that LPLN metastasis is not an important cause of local recurrence in patients with low rectal cancer. Therefore, Western approach is CRM-orientated and prophylactic LPLN dissection is not performed routinely as the NCCN guideline does not recommend its surgical removal unless metastases are clinically suspicious. The paradigm in Eastern countries differs somewhat. The Korean study demonstrated that adjuvant radiotherapy without lateral lymph node dissection was not enough to control local recurrence and LPLN metastases. The Japanese Trial JCOG 0212 demonstrated the effects of LPLN dissection in reducing local recurrence in the lateral pelvic compartment. We agree with Sammour and Chang on the fact that rather than a mutual exclusivity approach, we should claim for an approach where all available modalities are considered and used to optimize treatment outcomes, classifying patients into 3 categories of LPLN: low risk cT1/T2/earlyT3 (and Ra) with clinically negative LPLN on MRI; Moderate risk (cT3+/T4 with negative LPLN on MRI) and high risk (clinically abnormal LPLN on MRI). Treatment modality should be based on detailed pretreatment workup and an individualized approach that considers all options to optimize the treatment of patients with rectal cancer in the West or the East.

Project description:BackgroundPelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.MethodsWe conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects.ResultsFrom June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy.ConclusionsIn patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

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Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms.

Publications

Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms.

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