Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

Mihmanlı, Mehmet; Gürbulak, Esin Kabul; Akgün, İsmail; Celayir, Mustafa Fevzi; Yazici, Pınar; Tunçel, Deniz; Bek, Tuba Tulin; Öz, Ayhan; Ömeroğlu, Sinan

doi:10.4251/wjgo.v8.i9.695

Cited by 20 publications

(20 citation statements)

References 44 publications

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“…Both sphincter preservation (OR 1⋅00, 95 per cent c.i. 0⋅88 to 1⋅14; P = 0⋅95) and stoma formation (OR 1⋅06, 0⋅83 to 1⋅36; P = 0⋅63) rates were similar for the Tran et al 22 Tulchinsky et al 23 De Campos-Lobato et al 24 Wolthuis et al 25 Saglam et al 33 Jeong et al 43 You et al 44 Zeng et al 46 Sirohi et al 45 Mihmanlı et al 49 Akbar et al 26 Garrer et al 50 Tran et al 22 Stein et al 21 Tulchinsky et al 23 De Campos-Lobato et al 24 Wolthuis et al 25 Jeong et al 43 You et al 44 Zeng et al 46 Sirohi et al 45 Akbar et al 26 Garrer et al 50 11 longer versus shorter interval (Figs S8-S10, supporting information).…”

Section: Duration Of Surgery Sphincter Preservation and Covering Stomentioning

confidence: 82%

“…). A total of 26 publications, including four RCTs and 25 445 patients with rectal cancer were eligible for inclusion ( Table ). Twenty‐four of the 26 studies (22 650 patients) reported the primary endpoint of pCR based on the predefined wait interval and were included in the qualitative and quantitative analysis for this outcome variable; 15·9 per cent (1522 of 9551) and 11·3 per cent (1481 of 13 099) had achieved pCR in the extended and classical intervals respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Thirty-day mortality and local recurrence, distant metastasis, RFS and overall survival (OS) rates were also evaluated. Stein et al 21 Tran et al 22 Tulchinsky et al 23 De Campos-Lobato et al 24 Evans et al 32 Garcia-Aguilar et al 31 Wolthuis et al 25 Saglam et al 33 Jeong et al 43 You et al 44 Zeng et al 46 Sirohi et al 45 Probst et al 47 Mihmanlı et al 49 Timudom et al 48 Akbar et al 26 Lefevre et al 35 Kwak et al 51 Foster et al 34 Garrer et al 50 Lee et al 52 Kuan et al 53 Akgun et al 36 Kim et al 54…”

Section: Secondary Outcomesmentioning

confidence: 99%

“…There was no difference in reoperation (OR 1⋅25, 0⋅57 to 2⋅71; P = 0⋅58) or postoperative mortality (OR 1⋅13, 0⋅75 to 1⋅71, P = 0⋅56; risk difference of 0 per cent) rates between the groups ( Table 2) (Figs S11-S21, supporting information). Tran et al 22 Tulchinsky et al 23 De Campos-Lobato et al 24 Wolthuis et al 25 Saglam et al 33 Jeong et al 43 You et al 44 Zeng et al 46 Mihmanli et al 49 Akbar et al 26 Garrer…”

Section: Blood Loss Reoperation and Complication Ratesmentioning

confidence: 99%

“…De Campos-Lobato et al 24 Wolthuis et al 25 Saglam et al 33 Jeong et al 43 You et al 44 Zeng et al 46 Mihmanli et al 49 Akbar et al 26 Kim et al 54 305 of 1905 248 of 1739 1·02 (0·71, 1·45) 100·0 Total Heterogeneity: τ 2 = 0·16, χ 2 = 20·56, 9 d.f., P = 0·01, I 2 = 56% Test for overall effect: Z = 0·09, P = 0·93 0·1…”

Section: ·01mentioning

confidence: 99%

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Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

Ryan

O’Sullivan

Kelly

et al. 2019

British Journal of Surgery

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Background The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long‐course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6–8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. Methods A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8‐week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence‐free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta‐analysis was performed using the Mantel–Haenszel method. Results Twenty‐six publications, including four RCTs, with 25 445 patients were identified. A minimum 8‐week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). Conclusion A minimum 8‐week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence‐free survival without compromising surgical morbidity.

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Section: Duration Of Surgery Sphincter Preservation and Covering Stomentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Secondary Outcomesmentioning

confidence: 99%

Section: Blood Loss Reoperation and Complication Ratesmentioning

confidence: 99%

Section: ·01mentioning

confidence: 99%

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Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

Ryan

O’Sullivan

Kelly

et al. 2019

British Journal of Surgery

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Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study

Guzmán,

Ríos,

Paredes

et al. 2023

JAMA Surg

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ImportanceThe treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking.ObjectiveTo assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity.Design, Setting, and ParticipantsThis cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (&gt;8 and ≤12 weeks), and long (&gt;12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups.ExposureLong-course chemoradiotherapy or short-course radiotherapy with delayed surgery.Main outcome and MeasuresThe primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes.ResultsAmong the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group.Conclusions and RelevanceTime intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

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Gastrointestinal Malignancies and the COVID-19 Pandemic: Evidence-Based Triage to Surgery

Fligor

Wang

Allar

et al. 2020

Journal of Gastrointestinal Surgery

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Background The COVID-19 pandemic has led to widespread cancelation of electively scheduled surgeries, including for colorectal, pancreatic, and gastric cancer. The American College of Surgeons and the Society of Surgical Oncology have released guidelines for triage of these procedures. We seek to synthesize available evidence on delayed resection and oncologic outcomes, while also providing a critical assessment of the released guidelines. Methods A systematic review was conducted to identify literature between 2005 and 2020 investigating the impact of time to surgery on oncologic outcomes in colorectal, pancreatic, and gastric cancer. Results For colorectal cancer, 1066 abstracts were screened and 43 papers were included. In primarily resected colon cancer, delay over 30 to 40 days is associated with lower survival. In rectal cancer, time to surgery over 7 to 8 weeks following neoadjuvant therapy is associated with decreased survival. Three hundred ninety-four abstracts were screened for pancreatic cancer and nine studies were included. Two studies demonstrate increased unexpected progression with delayed surgery over 30 days. Out of 633 abstracts screened for gastric cancer, six studies were included. No identified study demonstrated worse survival with increased time to surgery. Conclusion Moderate evidence suggests that delayed resection of colorectal cancer worsens survival; the impact of time to surgery on gastric and pancreatic cancer outcomes is uncertain. Early resection of gastrointestinal malignancies provides the best chance for curative therapy. During the COVID-19 pandemic, prioritization of procedures should account for available evidence on time to surgery and oncologic outcomes.

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Delaying surgery after neoadjuvant chemoradiotherapy improves prognosis of rectal cancer

Cited by 20 publications

References 44 publications

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study

Gastrointestinal Malignancies and the COVID-19 Pandemic: Evidence-Based Triage to Surgery

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