Skip to main content

Symptomatic Recurrence and Survival Outcomes After Curative Treatment of Gastric Cancer: Does Intensive Follow-up Evaluation Improve Survival?

Annals of Surgical Oncology volume 29, pages 274–284 (2022)Cite this article

Abstract

Background

Intensive surveillance after treatment of gastric cancer patients with curative intent may lead to an earlier diagnosis of disease recurrence, but its impact on survival is uncertain. This study aimed to evaluate whether early diagnosis of disease recurrence among asymptomatic patients was associated with long-term survival.

Methods

This retrospective study analyzed patients with stages 1 to 3C gastric adenocarcinoma treated between 1999 and 2018. All recurrence events were classified as symptomatic or asymptomatic (detected by follow-up tests), and their clinicopathologic characteristics, patterns of recurrence, and survival were analyzed.

Results

The cohort consisted of 669 patients treated with a total gastrectomy in 48.6% and a D2-lymphadenectomy in 88.8% of the cases. Most of the tumors were pT3-4 (46.5%), with 45.5% involving lymph node metastases and 42.3% manifesting a diffuse histology. During a median follow-up period of 80.1 months (95% confidence interval [CI], 75.3–84.8 months), 166 patients had recurrences (24.8%), 65.7% of which were symptomatic. The peritoneum was the main site of recurrence (37.2%), and peritoneal recurrence was associated with worse overall survival (OS) (hazard ratio, 1.69; 95%CI, 1.2–2.37). The median disease-free, post-recurrence survival, and OS periods in the asymptomatic and symptomatic groups were respectively 13.4 versus 17.2 months (p = 0.04), 11.9 versus 4.7 months (p < 0.001), and 29.9 versus 26.4 months (p = 0.21). When OS was analyzed among the patients with non-peritoneal recurrence, no difference was observed between the two groups (31.3 vs 31.1 months; p = 0.46).

Conclusion

Early diagnosis of asymptomatic disease recurrence did not affect the OS of the gastric cancer patients treated with curative intent. The use of intensive surveillance strategies in this scenario still requires further evidence.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Moorcraft SY, Fontana E, Cunningham D, et al. Characterising timing and pattern of relapse following surgery for localized esophagogastric adenocarcinoma: a retrospective study. BMC Cancer. 2016;16:112.

    Article  Google Scholar 

  2. Peixoto RD, Lim HJ, Kim H, Abdullah A, Cheung WY. Patterns of surveillance following curative intent therapy for gastroesophageal cancer. J Gastrointest Cancer. 2014;45:325–33.

    CAS  Article  Google Scholar 

  3. Roviello F, Marrelli D, de Manzoni G, Morgagni P, Di Leo A, Saragoni L, De Stefano A. Prospective study of peritoneal recurrence after curative surgery for gastric cancer. Br J Surg. 2003;90:1113–9.

    CAS  Article  Google Scholar 

  4. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER-2-positive advanced gastric or gastroesophageal junction cancer (ToGA): a phase 3, open-label, randomized, controlled trial. Lancet. 2010;376:687–97.

    CAS  Article  Google Scholar 

  5. Kinoshita T, Kinoshita T, Saiura A, et al. Multicenter analysis of long-term outcome after surgical resection for gastric cancer liver metastases. Br J Surg. 2015;102:102–7.

    CAS  Article  Google Scholar 

  6. The GIVIO Investigators. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients: a multicenter randomized controlled trial. JAMA. 1994;271:1587–92.

    Article  Google Scholar 

  7. Wille-Jørgensen P, Syk I, Smedh K, et al. Effect of more vs less frequent follow-up testing on overall and colorectal cancer–specific mortality in patients with stage II or III colorectal cancer: the COLOFOL randomized clinical trial. JAMA. 2018;319:2095–103. https://doi.org/10.1001/jama.2018.5623.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cardoso R, Coburn NG, Seevaratnam R, et al. A systematic review of patient surveillance after curative gastrectomy for gastric cancer: a brief review. Gastric Cancer. 2012;15(Suppl 1):S164–7. https://doi.org/10.1007/s10120-012-0142-9.

    Article  PubMed  Google Scholar 

  9. National Comprehensive Cancer Network. Retrieved 15 January 2017 at https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.<PUB1>

  10. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. ESMO guidelines committee. Ann Oncol. 2016;27(Suppl 5):v38–49.

    CAS  Article  Google Scholar 

  11. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th ed). Gastric Cancer. 2020; https://doi.org/10.1007/s10120-020-01042-y. doi:https://doi.org/10.1007/s10120-020-01042-y. Published online ahead of print 14 February 2020.

  12. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectablegastroesophageal cancer. N Engl J Med. 2006;355:11–20.

    CAS  Article  Google Scholar 

  13. Brierley J, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 8th edn. Hoboken: Wiley; 2017.

    Google Scholar 

  14. Lauren P. The two histologic main types of gastric carcinoma: diffuse and so-called intestinal type carcinoma, an attempt at a histo-clinicalclassification. Acta ParholMicrob Scan. 1965;64:31–49.

    CAS  Article  Google Scholar 

  15. Dindo D, Demartines N, Clavien P-A. Classification of surgical complications. Ann Surg. 2004;240:205–13. https://doi.org/10.1097/01.sla.0000133083.54934.ae.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Shimada H, Noie T, Ohashi M, et al. Clinical significance of serum tumor markers for gastric cancer: a systematic review of the literature by the Japanese Gastric Cancer Association Task Force. Gastric Cancer. 2014;17:26–33. https://doi.org/10.1007/s10120-013-0259-5.

    CAS  Article  PubMed  Google Scholar 

  17. Pita-Fernández S, Alhayek-Aí M, González-Martín C, López-Calviño B, Seoane-Pillado T, Pértega-Díaz S. Intensive follow-up strategies improve outcomes in nonmetastatic colorectal cancer patients after curative surgery: a systematic review and meta-analysis. Ann Oncol. 2015;26:644–56. https://doi.org/10.1093/annonc/mdu543.

    Article  PubMed  Google Scholar 

  18. Jiang DM, Suzuki C, Espin-Garcia O, et al. Surveillance and outcomes after curative resection for gastroesophageal adenocarcinoma. Cancer Med. 2020;9:3023–32. https://doi.org/10.1002/cam4.2948.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhang N, Liu HX, Kang DM, Wang N. [Lead time bias and its control in observational studies for clinical outcomes]. Zhonghua Liu Xing Bing XueZaZhi. 2018;39:700–3. https://doi.org/10.3760/cma.j.issn.0254-6450.2018.05.032 (PMID: 29860822 (in Chinese)).

    CAS  Article  Google Scholar 

  20. Tan IT, So BY. Value of intensive follow-up of patients after curative surgery for gastric carcinoma. J Surg Oncol. 2007;96:503–6. https://doi.org/10.1002/jso.20823.

    Article  PubMed  Google Scholar 

  21. Kodera Y, Ito S, Yamamura Y, et al. Follow-up surveillance for recurrence after curative gastric cancer surgery lacks survival benefit. Ann Surg Oncol. 2003;10:898–902. https://doi.org/10.1245/aso.2003.12.009.

    Article  PubMed  Google Scholar 

  22. Fujiya K, Tokunaga M, Makuuchi R, et al. Early detection of nonperitoneal recurrence may contribute to survival benefit after curative gastrectomy for gastric cancer. Gastric Cancer. 2017;20(Suppl 1):141–9. https://doi.org/10.1007/s10120-016-0661-x.

    Article  PubMed  Google Scholar 

  23. Zanotti D, Baiocchi GL, Coniglio A, Mohammadi B, Ministrini S, Mughal M, et al. Follow-up after surgery for gastric cancer: how to do it. Updates Surg. 2018;70:293–9. https://doi.org/10.1007/s13304-018-0524-6 (PMID: 29582358).

    Article  PubMed  Google Scholar 

  24. Yamaguchi K, Yoshida K, Tanahashi T, Takahashi T, Matsuhashi N, Tanaka Y, et al. The long-term survival of stage IV gastric cancer patients with conversion therapy. Gastric Cancer. 2018;21:315–23. https://doi.org/10.1007/s10120-017-0738-1.

    CAS  Article  PubMed  Google Scholar 

  25. Al-Batran SE, Homann N, Pauligk C, et al. Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 trial. JAMA Oncol. 2017;3:1237–44. https://doi.org/10.1001/jamaoncol.2017.0515.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Al-Batran SE, Goetze TO, Mueller DW, et al. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer. 2017;17:893. https://doi.org/10.1186/s12885-017-3918-9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:2461–71. https://doi.org/10.1016/S0140-6736(17)31827-5 (PMID: 28993052).

    CAS  Article  PubMed  Google Scholar 

  28. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. (ToGA trial investigators). Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97. https://doi.org/10.1016/S0140-6736(10)61121-X (Epub 19 August 2010. Erratum in Lancet. 2010;376:1302. PMID: 20728210).

    CAS  Article  PubMed  Google Scholar 

  29. Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398:27–40. https://doi.org/10.1016/S0140-6736(21)00797-2 (Epub 5 June 2021 PMID: 34102137).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was founded in part by a Research Training Award for Cancer Prevention Post-graduate Training Program in Integrative Epidemiology from the Cancer Prevention & Research Institute of Texas, Grant No. RP160097 (PI: M. Spitz).

Author information

Authors and Affiliations

  1. Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil

    Thiago Pereira Diniz MD, Wilson L. da Costa Jr MD, PhD, MPH, Camila Couto Gomes MD, Silvio Melo Torres MD, Héber S. C. Ribeiro MD, PhD, Alessandro L. Diniz MD, André Luís de Godoy MD, Igor Correia de Farias MD & Felipe J. F. Coimbra MD, PhD

  2. Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Wilson L. da Costa Jr MD, PhD, MPH

  3. Department of Clinical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil

    Victor Hugo F. de Jesus MD & Tiago C. Felismino MD

  4. Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer Center, São Paulo, Brazil

    Emmanuel Dias-Neto MD, PhD

  5. Cancer Epidemiology and Statistics Group, International Research Center, A. C. Camargo Cancer Center, São Paulo, SP, Brazil

    Maria Paula Curado MD, PhD

Authors
  1. Thiago Pereira Diniz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wilson L. da Costa Jr MD, PhD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Camila Couto Gomes MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Victor Hugo F. de Jesus MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tiago C. Felismino MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Silvio Melo Torres MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Héber S. C. Ribeiro MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandro L. Diniz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. André Luís de Godoy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Igor Correia de Farias MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Emmanuel Dias-Neto MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maria Paula Curado MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Felipe J. F. Coimbra MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Felipe J. F. Coimbra MD, PhD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Diniz, T.P., da Costa, W.L., Gomes, C.C. et al. Symptomatic Recurrence and Survival Outcomes After Curative Treatment of Gastric Cancer: Does Intensive Follow-up Evaluation Improve Survival?. Ann Surg Oncol 29, 274–284 (2022). https://doi.org/10.1245/s10434-021-10724-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-021-10724-5

Keywords

  • Gastric cancer
  • Gastrectomy
  • Recurrence
  • Survival outcomes
  • Curative treatment
  • Follow-up