Oncologic Outcomes After Radical Surgery Following Preoperative Chemoradiotherapy for Locally Advanced Lower Rectal Cancer: Abdominoperineal Resection Versus Sphincter-Preserving Procedure

Purpose After preoperative chemoradiotherapy followed by total mesorectal excision for locally advanced rectal cancer, patients who experience local or systemic relapse of disease may be eligible for curative salvage surgery, but the benefit of this surgery has not been fully investigated. The purpose of this study was to characterize recurrence patterns and investigate the impact of salvage surgery on survival in patients with rectal cancer after receiving multidisciplinary treatment. Patients and Methods Patients with locally advanced (cT3-4 or cN+) rectal cancer who were treated with preoperative chemoradiotherapy followed by total mesorectal excision at our institution during 1993 to 2008 were identified. We examined patterns of recurrence location, time to recurrence, treatment factors, and survival. Results A total of 735 patients were included. Tumors were mostly midrectal to lower rectal cancer, with a median distance from the anal verge of 5.0 cm. The most common recurrence site was the lung followed by the liver. Median time to recurrence was shorter in liver-only recurrence (11.2 months) than in lung-only recurrence (18.2 months) or locoregional-only recurrence (24.7 months; P = .001). Salvage surgery was performed in 57% of patients with single-site recurrence and was associated with longer survival after recurrence in patients with lung-only and liver-only recurrence ( P < .001) but not in those with locoregional-only recurrence ( P = .353). Conclusion We found a predilection for lung recurrence in patients with rectal cancer after multidisciplinary treatment. Salvage surgery was associated with prolonged survival in patients with lung-only and liver-only recurrence, but not in those with locoregional recurrence, which demonstrates a need for careful consideration of the indications for resection.

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Comparison of efficacy and safety of preoperative Chemoradiotherapy in locally advanced upper and middle/lower rectal cancer

Radiation Oncology ◽

10.1186/s13014-018-0987-0 ◽

2018 ◽

Vol 13 (1) ◽

Cited By ~ 7

Author(s):

Ming-Yii Huang ◽

Hsin-Hua Lee ◽

Hsiang-Lin Tsai ◽

Ching-Wen Huang ◽

Yung-Sung Yeh ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Preoperative Chemoradiotherapy ◽

Lower Rectal Cancer ◽

Efficacy And Safety

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Randomized clinical trial of conventional versus cylindrical abdominoperineal resection for locally advanced lower rectal cancer

The American Journal of Surgery ◽

10.1016/j.amjsurg.2012.05.001 ◽

2012 ◽

Vol 204 (3) ◽

pp. 274-282 ◽

Cited By ~ 93

Author(s):

Jia Gang. Han ◽

Zhen Jun. Wang ◽

Guang Hui. Wei ◽

Zhi Gang. Gao ◽

Yong Yang ◽

...

Keyword(s):

Clinical Trial ◽

Rectal Cancer ◽

Randomized Clinical Trial ◽

Abdominoperineal Resection ◽

Locally Advanced ◽

Lower Rectal Cancer

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Oncologic outcomes of intersphincteric versus abdominoperineal resection for lower rectal cancer: A protocol for systematic review and meta-analysis

10.37766/inplasy2020.8.0111 ◽

2020 ◽

Author(s):

Wenming Yang ◽

Jianhao Zhang ◽

Zida Ma ◽

Xueting Liu ◽

Yongyang Yu ◽

...

Keyword(s):

Systematic Review ◽

Rectal Cancer ◽

Abdominoperineal Resection ◽

Meta Analysis ◽

Oncologic Outcomes ◽

Lower Rectal Cancer

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A multicenter phase I study on preoperative chemoradiotherapy with S-1 and CPT-11 for locally advanced lower rectal cancer (SAMRAI-1).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.503 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 503-503

Author(s):

Masafumi Noda ◽

Takeo Sato ◽

Kazushige Hayakawa ◽

Naohiro Tomita ◽

Norihiko Kamikonya ◽

...

Keyword(s):

Rectal Cancer ◽

Lymph Nodes ◽

Phase I ◽

Phase I Study ◽

Locally Advanced ◽

Preoperative Chemoradiotherapy ◽

Lower Rectal Cancer ◽

Level 3 ◽

Level 1 ◽

Level 2

503 Background: Preoperative chemoradiotherapy with 5-FU is a standard therapy for locally advanced lower rectal cancer. This therapy is useful for increasing local control rates and maintaining anal functions, but there is no evidence indicating that this therapy can extend survival. We performed a phase I study with the objective of developing a new chemoradiotherapy with irinotecan (CPT-11) and S-1, containing gimeracil, a dihydropyrimidine dehydrogenase inhibitor with radiosensitizing effect. Methods: Patients with locally advanced lower rectal cancer (T3-4, N0-2) of which the inferior border was located closer to the anal verge than to the peritoneal reflection were used for analysis. The radiation dose was 45 Gy in 25 fractions. The radiation field included the internal iliac, pararectal, and obturator lymph nodes in addition to the primary tumor and enlarged lymph nodes. S-1 was administered for five consecutive days and withdrawn for two consecutive days (administration: Days 1-5, 8-12, 22-26, and 29-33). The dose of S-1 (80, 100, 120 mg/day) was controlled in accordance with the body surface area. CPT-11 was administered on days 1, 8, 22, and 29. The initial dose of CPT-11 was 60 mg/m2 (Level 1), and the dose was increased gradually. Total mesorectal excision was performed 6-10 weeks after completion of the chemoradiotherapy. Results: 20 patients were enrolled. Excluding 2 patients who discontinued the study, 18 patients were subject to analysis. Dose-limiting toxicity (DLT) was not seen in 3 patients treated with CPT-11 at 80 mg/m2 (Level 2), but was seen in 3 of the 6 patients treated with CPT-11 at 90 mg/m2 (Level 3). DLT was seen in 3 other patients administered a Level 2 dose. At Level 2 or Level 3, DLTs, namely neutropenia, thrombocytopenia and diarrhea were seen. Level 2 was regarded as a maximum tolerated dose, and Level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the downstaging rate 56%. Conclusions: The results of the study suggest that the RD of CPT-11 is 60 mg/m2. We plan to perform a phase II study to evaluate the efficacy and safety of chemoradiotherapy with S-1 and CPT-11. Clinical trial information: UMIN000001639.

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A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer

Cancers ◽

10.3390/cancers12040800 ◽

2020 ◽

Vol 12 (4) ◽

pp. 800

Author(s):

In Ja Park ◽

Yun Suk Yu ◽

Bilal Mustafa ◽

Jin Young Park ◽

Yong Bae Seo ◽

...

Keyword(s):

Rectal Cancer ◽

Validation Cohort ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Gene Signature ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Oncologic Outcomes ◽

Tumor Biopsy ◽

Training Cohort

Preoperative chemoradiotherapy (PCRT) and subsequent surgery is the standard multimodal treatment for locally advanced rectal cancer (LARC), albeit PCRT response varies among the individuals. This creates a dire necessity to identify a predictive model to forecast treatment response outcomes and identify patients who would benefit from PCRT. In this study, we performed a gene expression study using formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 156 LARC patients (training cohort n = 60; validation cohort n = 96); we identified the nine-gene signature (FGFR3, GNA11, H3F3A, IL12A, IL1R1, IL2RB, NKD1, SGK2, and SPRY2) that distinctively differentiated responders from non-responders in the training cohort (accuracy = 86.9%, specificity = 84.8%, sensitivity = 81.5%) as well as in an independent validation cohort (accuracy = 81.0%, specificity = 79.4%, sensitivity = 82.3%). The signature was independent of all pathological and clinical features and was robust in predicting PCRT response. It is readily applicable to the clinical setting using FFPE samples and Food and Drug Administration (FDA) approved hardware and reagents. Predicting the response to PCRT may aid in tailored therapies for respective responders to PCRT and improve the oncologic outcomes for LARC patients.

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