Great Debates & Updates in GI Malignancies
March 28-29, 2014
DEBATE: What is the Optimal Sequence of Therapies for
Stage II-III Adenocarcinoma of the Proximal Stomach?
Surgery Followed By Adjuvant
Chemoradiation Therapy
Michael A. Choti, MD
Department of Surgery
UT Southwestern Medical Center

Disclosures none

GE junction / Gastric Cardia Tumors
• Making the distinction between lower esophageal
CA can be problematic
• Rising in incidence
• Poorer prognosis
• Resection: esophagogastrectomy vs. total gastrectomy

Treatment of Localized Gastric Cancer
1.
Surgical therapy is the only means of cure and is the treatment of choice for early stage disease.
2.
Endoscopic mucosal resection (EMR) is reserved for T1a disease.
3.
Goal is complete resection with negative margins (R0).
4.
Emerging role of laparoscopic resection for gastric and esophageal cancer.
5.
Proximal cancer: total gastrectomy vs. esophagogastrectomy.

D1 vs D2 Lymphadenectomy

Minimally Invasive Gastrectomy
• Emerging as treatment of choice in many centers
• Outcomes appear comparable
• Important to ensure the same (or better) oncologic outcome that is possible with open surgery (including D2)
Kim et al. Ann Surg 2010
KLASS Trial. RCT comparing open vs lap gastrectomy
No difference in short term outcomes
Chen et al. World J Surg 2013
Meta-analysis comparing lap vs open gastrectomy
Enhanced recovery with no difference in long-term outcome

Rationale for Preoperative Therapy in
Proximal Gastric Cancer
• Studies demonstrating benefit of preoperative chemotherapy over surgery alone 1
• Evidence of role of induction chemoradiation therapy in distal esophageal CA 2
1
MAGIC Trial. Cunningham et al. Radiother Oncol 104 (2012)
2 CROSS Trial. van Hagen et al. NEJM (2012)

Importance of Preoperative Staging
When Considering Neoadjuvant Therapy
• Accuracy of predicting nodal involvement is
60-80%
• Surgery alone may be sufficient for Stage II disease
• Neoadjuvant therapy may be overtreating some patients

Rationale for Up Front Surgery in
Patients With Gastric Cancer
• Pathologic staging may result in more appropriate choice of adjuvant therapy (accurate stage II vs III, D1 vs D2, margins).
• Symptomatic patients may require initial surgery.
• In reality, gastrectomy is often performed before
MDT consultation.

Algorithm for Management of Gastric Cancer*
*ESMO-ESSO-ESTRO 2013

Chemoradiation After Surgery Versus Surgery Alone for
Gastric and GEJ Adenocarcinoma
MacDonald et al. NEJM 2001
• 20% GE Junction
• Criticized for inadequate surgical radicality

Impact of Extent of Surgery and Postop Chemoradiation:
Dutch Gastric Cancer Group Trial
D1
D2
Dikken et al. JCO May 2010

Post-Operative Chemo vs Chemoradiation:
ARTIST Trial
• Samsung University
• 458 patient RCT
• D2 gastrectomy
• ~5% proximal CA
Postoperative adjuvant
Cap-Cis ± RT
• No difference in DFS
• No difference in locoregional rec
Lee et al. JCO Jan 2012

Post-Operative Chemo vs Chemoradiation:
Nanjing University
Recurrence-Free Survival
P=0.029
• 380 patients
• Randomized trial
• All D2 gastrectomy
• ~10% GE junction
Postoperative adjuvant
5FU-LV ± IMRT
• Improved RFS with
IMRT (50 vs 32 mo)
• No difference in OS
Zhu et al. Radiother Oncol 104 (2012)

CRITICS Study
Preoperative
Chemotherapy
3x ECC q 3 wks
D1+ Surgery 3x ECC q 3 wks
R
Preoperative
Chemotherapy
3x ECC q 3 wks
2 weeks
D1+ Surgery
3-6 weeks
Chemoradiotherapy
45 Gy/25 fx
+ capecitabine
+ cisplatin
Within 4-12 weeks

Adjuvant Therapy for Proximal Gastric Cancer
Summary
1. While preoperative therapy may be preferred in most cases, initial gastrectomy is being commonly performed.
2. While R0 gastrectomy with D2 lymphadenectomy is recommended, less radical surgery is common.
3. Chemoradiation appears to have a role in reducing local recurrence.
4. Postoperative chemoradiation should be considered when managing a post-op patient, particularly when
<D2 gastrectomy was performed.