Ann Surg Treat Res.  2022 Dec;103(6):350-359. 10.4174/astr.2022.103.6.350.

The watch-and-wait strategy versus radical resection for rectal cancer patients with a good response (≤ycT2) after neoadjuvant chemoradiotherapy

• Lee C
• Park IJ
• Lim SB
• Yu CS
• Kim JC

• KMID: 2536911
• DOI: http://doi.org/10.4174/astr.2022.103.6.350

Abstract

Purpose
This study aims to oncologic outcomes of the watch-and-wait (WW) strategy compared with radical resection (RR).
Methods
Patients with rectal cancer who received neoadjuvant chemoradiotherapy (nCRT) and achieved ≤ycT2 between 2008 and 2016 were included. The mean follow-up time was 61 months (range, 0–168 months). Recurrence-free survival (RFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were compared. A total of 446 patients were included, and WW was adopted for 34 patients.
Results
WW patients were older (P = 0.022) and less advanced initial cT stage (P = 0.004). Ten patients in the WW group (29.4%) experienced local regrowth. Later, distant metastases occurred in 7 of these patients. The 5-year RFS (74.1% vs. 79.5%), DMFS (74.1% vs. 81.6%), and OS (90.4% vs. 87.7%) for the WW and RR groups were not statistically different. However, LRFS in the WW group was significantly lower (65.1% vs. 97.0%, P < 0.001). The initial cT stage was associated with RFS (P = 0.019) and LRFS (P = 0.037). WW was an independent risk factor for LRFS (P < 0.001) and DMFS (P = 0.024). After 1:4 propensity score matching between the WW and RR groups, there was no difference in RFS and OS. However, the 5-year LRFS (67.5% vs. 96.5%) and DMFS (73.2% vs. 86.4%) demonstrated a statistically significant difference between the groups.
Conclusion
By appointing the WW strategy, oncologic safety was not ensured. The WW strategy must be implemented with caution in patients with ≤ycT2 stage, particularly those with advanced initial cT stage.

Keyword

Good responder; Neoadjuvant therapy; Radical resection; Rectal neoplasms; Watch-and-wait

Figure

• 

  Fig. 1 Inclusion and exclusion criteria for the overall cohort. nCRT, neoadjuvant chemoradiotherapy; FAP, familial adenomatous polyposis; HNPCC, hereditary nonpolyposis colon cancer; RR, radical resection; WW, watch-and-wait.

• 

  Fig. 2 Surveillance protocol in radical resection (RR) and watch-and-wait (WW) group. DRE, digital rectal examination.

• 

  Fig. 3 Oncologic outcomes according to treatment strategies; watch-and-wait (WW) vs. radical resection (RR). (A, C, D) Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) did not differ between WW and RR groups. (B) Local recurrence-free survival (LRFS) was significantly low in the WW group.

• 

  Fig. 4 Timing of recurrence and metastasis in the watch-and-wait (WW) group.

• 

  Fig. 5 Oncologic outcomes according to the treatment strategies in the propensity score matched group. (A) Recurrence-free survival (RFS) and (D) overall survival (OS) were not different between groups. But, (B) local recurrence-free survival (LRFS) and (C) distant metastasis-free survival (DMFS) were significantly lower in the watch-and-wait (WW) group than in the radical resection (RR) group.

Reference

1. Manceau G, Karoui M, Werner A, Mortensen NJ, Hannoun L. Comparative outcomes of rectal cancer surgery between elderly and non-elderly patients: a systematic review. Lancet Oncol. 2012; 13:e525–e536. PMID: 23182193.

2. Mrak K, Eberl T, Laske A, Jagoditsch M, Fritz J, Tschmelitsch J. Impact of postoperative complications on long-term survival after resection for rectal cancer. Dis Colon Rectum. 2013; 56:20–28. PMID: 23222276.

3. Kim S, Kang SI, Kim SH, Kim JH. The effect of anastomotic leakage on the incidence and severity of low anterior resection syndrome in patients undergoing proctectomy: a propensity score matching analysis. Ann Coloproctol. 2021; 37:281–290. PMID: 34098631.

4. Erlandsson J, Pettersson D, Glimelius B, Holm T, Martling A. Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy. Br J Surg. 2019; 106:1248–1256. PMID: 31197822.

5. Guren MG, Wiig JN, Dueland S, Tveit KM, Fosså SD, Waehre H, et al. Quality of life in patients with urinary diversion after operation for locally advanced rectal cancer. Eur J Surg Oncol. 2001; 27:645–651. PMID: 11669593.

6. Näsvall P, Dahlstrand U, Löwenmark T, Rutegård J, Gunnarsson U, Strigård K. Quality of life in patients with a permanent stoma after rectal cancer surgery. Qual Life Res. 2017; 26:55–64. PMID: 27444778.

7. Park IJ, Yu CS. Current issues in locally advanced colorectal cancer treated by preoperative chemoradiotherapy. World J Gastroenterol. 2014; 20:2023–2029. PMID: 24587677.

8. Varela C, Kim NK. Surgical treatment of low-lying rectal cancer: updates. Ann Coloproctol. 2021; 37:395–424. PMID: 34961303.

9. Huh JW, Maeda K, Liu Z, Wang X, Roslani AC, Lee WY. Current status of “watch-and-wait” rectal cancer treatment in Asia-Pacific countries. Ann Coloproctol. 2020; 36:70–77. PMID: 32054250.

10. Park IJ, Lee JL, Yoon YS, Kim CW, Lim SB, Yu CS, et al. Oncologic outcomes of organ preserving approaches in patients with rectal cancer treated with preoperative chemoradiotherapy. Ann Coloproctol. 2019; 35:65–71. PMID: 31113171.

11. Oh SG, Park IJ, Seo JH, Kim YI, Lim SB, Kim CW, et al. Beware of early relapse in rectal cancer patients treated with preoperative chemoradiotherapy. Ann Coloproctol. 2020; 36:382–389. PMID: 32674549.

12. Kasi A, Abbasi S, Handa S, Al-Rajabi R, Saeed A, Baranda J, et al. Total neoadjuvant therapy vs standard therapy in locally advanced rectal cancer: a systematic review and meta-analysis. JAMA Netw Open. 2020; 3:e2030097. PMID: 33326026.

13. Petrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, et al. Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg. 2020; 271:440–448. PMID: 31318794.

14. Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol. 2016; 17:174–183. PMID: 26705854.

15. Dossa F, Chesney TR, Acuna SA, Baxter NN. 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. 2017; 2:501–513. PMID: 28479372.

16. Park SH, Cho SH, Choi SH, Jang JK, Kim MJ, Kim SH, et al. MRI assessment of complete response to preoperative chemoradiation therapy for rectal cancer: 2020 guide for practice from the Korean Society of Abdominal Radiology. Korean J Radiol. 2020; 21:812–828. PMID: 32524782.

17. Gambacorta MA, Masciocchi C, Chiloiro G, Meldolesi E, Macchia G, van Soest J, et al. Timing to achieve the highest rate of pCR after preoperative radiochemotherapy in rectal cancer: a pooled analysis of 3085 patients from 7 randomized trials. Radiother Oncol. 2021; 154:154–160. PMID: 32966845.

18. Kong JC, Guerra GR, Warrier SK, Ramsay RG, Heriot AG. Outcome and salvage surgery following “watch and wait” for rectal cancer after neoadjuvant therapy: a systematic review. Dis Colon Rectum. 2017; 60:335–345. PMID: 28177997.

19. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004; 240:711–718. PMID: 15383798.

20. Perez RO, Habr-Gama A, São Julião GP, Proscurshim I, Fernandez LM, de Azevedo RU, et al. Transanal endoscopic microsurgery (TEM) following neoadjuvant chemoradiation for rectal cancer: outcomes of salvage resection for local recurrence. Ann Surg Oncol. 2016; 23:1143–1148. PMID: 26577119.

21. Martens MH, Maas M, Heijnen LA, Lambregts DM, Leijtens JW, Stassen LP, et al. Long-term outcome of an organ preservation program after neoadjuvant treatment for rectal cancer. J Natl Cancer Inst. 2016; 108:djw171. PMID: 27509881.

22. Perez RO, Habr-Gama A, São Julião GP, Proscurshim I, Scanavini Neto A, Gama-Rodrigues J. Transanal endoscopic microsurgery for residual rectal cancer after neoadjuvant chemoradiation therapy is associated with significant immediate pain and hospital readmission rates. Dis Colon Rectum. 2011; 54:545–551. PMID: 21471754.

23. Hiotis SP, Weber SM, Cohen AM, Minsky BD, Paty PB, Guillem JG, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg. 2002; 194:131–136. PMID: 11848629.

24. Marijnen CA. Organ preservation in rectal cancer: have all questions been answered? Lancet Oncol. 2015; 16:e13–e22. PMID: 25638548.

25. Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022; 40:2546–2556. PMID: 35483010.

26. Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ Jr. Total neoadjuvant therapy: a shifting paradigm in locally advanced rectal cancer management. Clin Colorectal Cancer. 2018; 17:1–12. PMID: 28803718.

27. Fernandez LM, Figueiredo NL, Habr-Gama A, São Julião GP, Vieira P, Vailati BB, et al. Salvage surgery with organ preservation for patients with local regrowth after watch and wait: is it still possible? Dis Colon Rectum. 2020; 63:1053–1062. PMID: 32692070.

28. Fernandez LM, São Julião GP, Vailati BB, Habr-Gama A, Perez RO. Nonoperative management for T2 low rectal cancer: a Western approach. Clin Colon Rectal Surg. 2020; 33:366–371. PMID: 33162841.

29. Patel UB, Blomqvist LK, Taylor F, George C, Guthrie A, Bees N, et al. MRI after treatment of locally advanced rectal cancer: how to report tumor response: the MERCURY experience. AJR Am J Roentgenol. 2012; 199:W486–W495. PMID: 22997398.

30. Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010; 53:1692–1698. PMID: 21178866.