Abstract
Background
Watch-and-Wait (WW) approach is positioned at the cutting edge of non-invasive approach for rectal cancer patients who achieve clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT). This meta-analysis aimed to compare the clinical, oncologic, and survival outcomes of WW versus radical surgery (RS) and to evaluate the efficacy, safety, and possible superiority of WW.
Methods
A systematic search for studies comparing WW with RS was conducted on MEDLINE, Ovid, Embase, Cochrane Library, and Web of Science databases. After screening for inclusion, data extraction, and quality assessment, statistical analysis was performed using Stata/SE14.0 software. Permanent colostomy (PC), local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), 2-, 3-, and 5-year disease-free survival (DFS), and overall survival (OS) were analyzed using fixed effects or random-effects models depending on the heterogeneity.
Results
Fourteen studies with moderate-high quality involving 1254 patients were included. Of these, 513 patients were managed with WW and 741 patients were subjected to RS. Compared to RS group, WW group had higher rate of LR (odds ratio OR = 11.09, 95% confidence interval CI = 5.30–23.20, P = 0.000), 2-year OS, and 3-year OS and had lower rate of PC (OR = 0.12, 95% CI = 0.05–0.29, P = 0.000). There were no significant between-group differences with respect to DM, CRD, 2-, 3-, and 5-year DFS (OR = 0.92, 95% CI = 0.81–1.03, P = 0.153), or 5-year OS (OR = 1.01, 95% CI = 0.28–3.63, P = 0.988).
Conclusion
The WW is a promising treatment approach and is a relatively safe alternative to RS for managing patients with rectal cancer who achieve cCR after nCRT. However, this modality requires rigorous screening criteria and standardized follow-up. Large-scale, multicenter prospective randomized controlled trials are warranted to further verify the outcomes of WW approach.
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References
Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clini. https://doi.org/10.3322/caac.21660
Siegel RL, Miller KD et al (2020) (2020) Colorectal cancer statistics. CA Cancer J Clin 70(3):145–164. https://doi.org/10.3322/caac.21601
Heald RJ, Husband EM, Ryall RD (1982) The mesorectum in rectal cancer surgery–the clue to pelvic recurrence? Br J Surg 69:613–616
Fujita S, Akasu T, Mizusawa J et al (2012) Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage or stage III lower rectal cancer (JCOG0212): results from a multicenter, randomized controlled, non-inferiority trial. Lancet Oncol 13(6):616–621
Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30(16):1926–1933
Harrison JD, Solomon MJ, Young JM et al (2008) Patient and physician preferences for surgical and adjuvant treatment options for rectal cancer. Arch Surg 143(4):389–394
Rödel C, Liersch T, Becker H et al (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer initial results of the German CAO/ARO/AIO⁃04 randomised phase 3 trial. Lancet Oncol 13(7):679–687
Paun BC, Cassie S, Maclean AR (2010) Postoperative complications following surgery for rectal cancer. Ann Surg 251(5):807–818
Lange MM, Maas CP, Marijnen CA et al (2008) Urinary dysfunction after rectal cancer treatment is mainly caused by surgery. Br J Surg 95(8):1020–1028
Hendren SK, O’Connor BI, Liu M et al (2005) Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg 242(2):212–223
Juul T, Ahlberg M, Biondo S et al (2014) Low anterior resection syndrome and quality of life an international multicenter study. Dis Colon Rectum 57(5):585–591
Glynne-Jones R, Hughes R (2016) Complete response after Chemoradiotherapy in Rectal cancer (Watch-and-Wait) Have we Cracked the Code? Clin Oncol (R Coll Radio) 28(2):152–160
Mass M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer a pooled analysis of individual patient data. Lancet Oncol 11(9):835–844
Nakagawa WT, Rossi BM et al (2002) Chemoradiation instead of surgery to treat mid and low rectal tumors: is it safe? Ann Surg Oncol 9(6):568–573
Habr-Gama A, Perez RO, Nadalin W et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long term results. Ann Surg 240(4):711–717
Appelt JP et al (2015) High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 16(8):919–927
Habr-Gama A et al (2014) Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys 88(4):822–828
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71
Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539
Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Ayloor Seshadri R, Kondayeeti SS et al (2013) Complete clinical response to neoadjuvant chemoradiation in rectal cancers: can surgery be avoided? Hepatogastroenterology 60(123):410–414
Smith RK, Fry RD, Mahmoud NN et al (2015) Surveillance after neoadjuvant therapy in advanced rectal cancer with complete Clinical response can have comparable outcomes to total mesorectal excision. Int J Colorectal Dis 30(6):769–774
Lai CL, Lai MJ, Wu CC et al (2016) Rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy, surgery, or, ”watch and wait”. Int J Colorectal Dis 31(2):413–419
Yeom SS et al (2019) Non-operative treatment outcome for rectal cancer patient with clinical complete response after neoadjuvant chemoradiotherapy. Asian J Surg 42(8):823–831
Neşşar G et al (2019) Watch and wait approach in rectal cancer patients following complete clinical response to neoadjuvant chemoradiotherapy does not compromise oncologic outcomes. Turk J Gastroenterol 30(11):951–956
Smith JJ et al (2019) Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy. JAMA Oncol 5(4):e185896
Mass M, Beets-Tan RG, Lammering G et al (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29(35):4633–4640
Dalton RS, Velineni R et al (2012) A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management? Colorectal Dis 14:567–571
Smith JD, Ruby JA, Goodman KA et al (2012) Nonoperative management of rectal cancer with complete clinical response After Neoadjuvant Therapy. Ann Surg 256(6):965–972
Li J, Liu H, Yin J et al (2015) Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study. Oncotarget 6(39):4235–4261
Lee SY, Kim CH et al (2015) Oncologic Outcomes according to Treatment Strategy in Radiologic Complete Responders after Neoadjuvant Chemoradioation for Rectal Cancer. Oncology 89(6):311–318
Araujo RO, Valadão M, Borges D et al (2015) Nonoperative management of rectal cancer after chemoradiation opposed to resection after complete clinical response. A comparative study. Eur J Surg Oncol 41(11):1456–1463
Renehan AG, Malcomson L, Emsley R et al (2016) Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (theOnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 17(2):174–183
Dinaux AM, Amri R et al (2017) The impact of pathologic complete response in patients with neoadjuvantly treated locally advanced rectal cancer-a large single-center experience. J Gastrointest Surg 21(7):1153–1158
Bipat S, Glas AS et al (2004) Rectal cancer: local staging and assessment of lymph node involvement with endoluminal US, CT, and MR imaging-a meta-analysis. Radiology 232(3):773–783
Habr GA, Sabbaga J, Gama-Rodrigues J et al (2013) Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon Rectum 56(10):1109–1117
van der Valk MJM, Hilling DE et al (2018) Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet 23(391):2537–2545
Dossa F (2017) Tyler R Chesney, Sergio A Acuna, Nancy N Baxter (2017) A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2(7):501–513
Zhao G-H, Deng Li et al (2020) Efficacy and safety of wait and see strategy versus radical surgery and local excision for rectal cancer with cCR response after neoadjuvant chemoradiotherapy: a meta-analysis. World J Surg Oncol 18(1):232
Rullier E, Rouanet P et al (2020) Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet 390:469–479
Stijns RCH, de Graaf EJR et al (2019) Long-term oncological and functional outcomes of chemoradiotherapy followed by organ-sparing transanal endoscopic microsurgery for distal rectal cancer: the carts study. JAMA Surg 154:47–54
Smith FM, Rao C et al (2015) Avoiding radical surgery improves early survival in elderly patients with rectal cancer, demonstrating complete clinical response after neoadjuvant therapy: results of a decision-analytic model. Dis Colon Rectum 58(2):159–171
Machackova T et al (2020) Tumor microRNAs Identified by Small RNA sequencing as potential response predictors in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy. Cancer Genomics Proteomics 17(3):249–257
De Palma FDE et al (2020) The role of Micro-RNAs and circulating tumor markers as predictors of response to neoadjuvant therapy in locallyadvanced rectal cancer. Int J Mol Sci 21(19):7040
Troncarelli Flores BC et al (2019) Molecular and kinetic analyses of circulating tumor cells as predictive markers of treatment response in locally advanced rectal cancer patients. Cells 8(7):641
Silva VSE et al (2021) Molecular and dynamic evaluation of proteins related to resistance to neoadjuvant treatment with chemoradiotherapy in circulating tumor cells of patients with locally advanced rectal cancer. Cells 10(6):1539
Funding
This study was supported by the National Natural Science Foundation of China (82060542) and the Yunnan Provincial Science and Technology Department (008106293057), the Yunnan Education Department Project.
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XZ, RD, and YFL contributed substantially to study design. XZ, JSL, GYL, and ZJS contributed to data extraction, quality assessment, and data analysis. XZ and SSL contributed to manuscript writing and edition. YZ, TW, and CD revised the manuscript for its integrity and accuracy. ZJS, TL, and HZ approved the final version of this manuscript and take responsibility for its content. All authors read and approved the final manuscript.
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Xuan Zhang, Rong Ding, JinSha Li, Tao Wu, ZhengHai Shen, ShanShan Li, Ya Zhang, Chao Dong, ZhongJun Shang, Hai Zhou, Ting Li, GuoYu Li, and YunFeng Li have no conflict of interest or financial ties to disclose.
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Zhang, X., Ding, R., Li, J. et al. Efficacy and safety of the “watch-and-wait” approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a meta-analysis. Surg Endosc 36, 2233–2244 (2022). https://doi.org/10.1007/s00464-021-08932-x
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DOI: https://doi.org/10.1007/s00464-021-08932-x