Surveillance of Gastric Cancer Shahid Ahmed Saskatoon Cancer Center, Saskatchewan Cancer Agency Case RM is a 62 year old very pleasant secratary with no major medical history diagnosed with clinically stage 2 gastric cancer. She received 3 cycles of pre op ECF (epirubicin, cisplatin and 5 FU) and underwent surgery. Post operative pathology showed ypt4an2 stage 3 disease. After discussion with RM 3 additional cycles of ECF was given. Her five year risk of recurrence is more than 50%. What follow up would you recommend for her? 1
Gastric cancer is the fourth most common cancers and second leading cause of cancer deaths worldwide. Globally it accounts for 8% of the total cases of cancer and 10% of total cancer related deaths. Siegel R et al. Cancer statistics, 2013. CA Cancer J Clin 2013; 63:11. Facts Gastric cancer has a high recurrence rate following the curative resection. Majority of the recurrences occur within five years following surgery 70% relapse within 2 3 years after surgery More than 90% of patients relapse within 5 years The reported incidence of metachronous gastric cancer after partial gastrectomy for early gastric cancer is 0.6 3% Surgery with a curative intention after loco regional recurrence can only be performed in a very limited number of patients. Marrelli D, et al. Ann Surg. 2005;241(2):247 55. Kodera Y, et al. Ann Surg Oncol 2003; 10: 898 902. 2
Feeding problems occur in approximately 30% of patients, but severe symptoms are present only in 1 2%. There are various postgastrectomy syndromes based on the type of surgery and reconstruction technique. Anemia, bone disease, and weight loss due to malabsorption are not uncommon. Iron deficiency is the most common anemia following gastric resection. Important goals of follow up Identification and management of treatment related complications. Early recognition and treatment of potentially curable disease recurrences and a second primary cancer. Identification of symptoms related to metastatic disease and appropriate work up and referral to specialists for further management. 3
Surveillance Components History & Physical Examination Beneficial for identification and treatment of surgery ± chemotherapy/radiation related complications. Routine assessment in asymptomatic patients are not useful for detection of recurrence. Whiting et al. Gastric Cancer 2006;9:74 81. D Ugo et al. Dig Surg 2013;30:159 168 4
Endoscopic Exam Endoscopy during the follow up period is considered when there is a risk of recurrence in the stomach remnant: after a subtotal gastrectomy after endoscopic treatment for early gastric cancer For early gastric cancers, endoscopy can detect new primaries, but the incidence of these tumors is low. Many thousands of procedures are required to detect each operable case. Kato M et al. Gut 2013;62:1425. Nishida T, et al. World J Gastrointest Pathophysiol. 2014;5:100 6 CT Scan CT scan is regarded as the most reliable method for assessing cancer recurrence, with a reported accuracy of 60 70%. Limited value in the distinction of postoperative morphologic changes from tumor recurrence. Low positive predictive value for peritoneal and distant lymph node metastasis Kim JH, et al. J Gastrointest Surg 2010; 14: 969 976. Kim KW, et al. Radiographics 2002; 22: 323 336. 5
PET CT Scan A PET CT scan has a diagnostic accuracy ranging from 75 to 97%. Greatest utility in patients with a suspicion of recurrences based on tumor marker and other imaging modalities. Sim SH, et al. BMC Cancer 2009;9: 73. Ozkan E, et al. World J Surg Oncol 2011; 9: 75. Tumor Markers CEA and CA19 9 are potentially useful indicators of recurrence, especially in the patients who had elevated preoperative levels of these markers. Takahashi Y, et al. Gastric Cancer 2003; 6: 142 145. Choi SR, et al. Dig Dis Sci 2006; 51: 2081 2086. 6
Post Recurrence Outcomes Colorectal Cancer Median survival 24 30 months 10 20 % can undergo metastasectomy Loco regional therapies are option in some cases Long term remission/ cure can be achieved in 30 40% patients with metastasectomy Gastric Cancer Median survival approximately 12 months Curative surgery is rarely an option Loco regional therapies are not feasible in most cases long term survival is extremely rare following metastases resection Wei AC, et al. Ann Surg Oncol 2006; 13:668, Morris EJ et al. Br J Surg 2010; 97:1110. Evidence From Literature 7
There are no randomized trials to guide surveillance strategies following remission from early gastric cancer. All of the recommendations on surveillance are based on low level evidence or no evidence at all. Incidence of synchronous gastric cancers in the endoscopically resected tumors within 1 yr of the procedure Arima et al, 1999 6.6% 5/76.. Nasu et al, 2005 11% 16/143.. Nakajima et al, 2006 9.2% 58/633.. Kobayashi et al, 2010 19.2% 45/234.. Han et al, 2011 4% 7/176.. Kato et al, 2013 8.7% 110/1258 19% (21/110) Kim et al, 2013 2% 12/602 Arima N, et al. J Clin Gastroenterol.1999;29:44 47. Nasu J, et al. Endoscopy. 2005;37:990 993. Nakajima T, et al. Gastric Cancer. 2006;9:93 98. Kobayashi M, et al. Dig Endosc. 2010;22:169 173. Han JS, et al. Scand J Gastroenterol.2011;46:1099 1104. Kato M, et al. Gut. 2013;62:1425 1432. Kim HH, et al. Dig Endosc.2013;25:32 38 8
Surveillance after ESD A retrospective cohort study from Japan involving 1258 patients with early gastric cancer treated with endoscopic submucosal dissection (ESD). Post ESD surveillance endoscopy every 6 12 months. At median follow up of 27 months, synchronous ( one year of ESD) or metachronous (> one year) cancers were detected in 14% cases, and local recurrence was detected in 0.4%. 94% were successfully treated with repeat ESD. Kato M et al. Gut 2013;62:1425. A retrospective study conducted in Korea suggests that there is no difference in outcomes for subjects screened at one, two, or three year intervals. The exact surveillance interval needs to be defined with randomized trials. Park CH, et al. Gastrointest Endosc 2014; 80:253. 9
Surveillance after gastrectomy Patients with symptomatic recurrence have more aggressive disease with a shorter postrecurrence survival. Bennett JJ, et al. J Am Coll Surg.2005;201503 10, Bilici A et al. J Surg Res. 2013;180(1):e1 9. Kim JH, et al. J Gastrointest Surg 2010; 14: 969 976. Systematic Review A Systemic review of 5 observational studies involving 810 patients who underwent postoperative follow up. History and physical examination, hematological and chemistry profile, EGD, and CT were the most frequently employed modalities. CT detected the majority of recurrences in the included studies. Cardoso et al. Gastric Cancer (2012) 15 (Suppl 1):S164 S167 10
Study N Recurrence DFS P SPR P OS p Bennett AG=99 SG=283 99 238 10.8 12.4 NS 13.5 4.8 <0.01 Bohner AG=15 SG=52 15 52 13 13 7 5 Kodera AG=88 SG=109 88 109 30 30 0.2 29 25 <0.001 51.7 40 0.19 Mikani 62 22.2 13.7 27.5 Tan SG=49 AG=53 24 23 11.5 19.2 0.02 0.001 49.2 45.6 0.46 Tan et al. J Surg Oncol. 2007;96:503 6. Mikani et al. Chir Gastroenterol. 2007;23:392 8. Bennett et al. J Am Coll Surg. 2005;201(4):503 510. Bohner et al. Hepatogastroenterology. 2000;47:1489 94. Kodera et al. Ann Surg Oncol. 2003;10(8):898 902. The survival post recurrence was significantly higher in the asymptomatic group compared with symptomatic group in three studies, this likely reflects lead time bias, in which the observed prolonged survival is due to earlier detection of recurrence, rather than being due to a true effect on disease outcome. No differences in overall survival (OS) were found. 11
Guidelines Recommendations 2015 NCCN Gastric Cancer Follow Up Recommendations H & P Every 3 6 months for 1 2 yrs Every 6 12 months for 3 5 yrs then annually CBC and chemistry profile as indicated Radiologic imaging or endoscopy as clinically indicated Monitor nutritional deficiency (e.g. B12 and iron) in surgically resected patients and treated as indicated 12
2013 ESMO Gastric Cancer Surveillance In the setting of operable gastric cancer, the complexity of treatment frequently induces symptoms which adversely affect health related quality of life. A regular follow up may allow investigation and treatment of symptoms, psychological support and early detection of recurrence, though there is no evidence that it improves survival outcomes. New strategies for patient follow up are currently undergoing evaluation, including patient led selfreferral and services led by clinical nurse specialists. 2014 Saskatchewan Cancer Agency Follow up investigations should be tailored based on disease stage, adjuvant treatment provided, performance status, and clinical signs and symptoms. In patients treated with curative intent: history and physical examination every 3 6 months for the first 3 years then every 6 12 months for the next 2 years and annually thereafter. Thoracoabdominal CT scan, abdominal ultrasound and chest x ray only as clinically indicated. Periodic endoscopic examination as clinically indicated. Laboratory testing including CBC, serum chemistry, LFT, and CEA only as clinically indicated. Nutritional counseling for all; vitamin B12 supplementation in patients who have had proximal or total gastrectomy. 13
Conclusions Currently the best strategy for the follow up of patients who have undergone surgical treatment with curative intent for gastric cancer is not known. Period assessments are useful to address treatmentrelated complications and psychological support. Currently there are no data to support that early detection of an asymptomatic recurrence by tumor marker or radiologic imaging improves quality of life or prolongs survival. 14