Effectiveness of Surgery for GIST
Prior to the introduction of targeted molecular drug therapies (starting with imatinib/Gleevec), surgery was the only useful treatment for GIST. Surgery is still the cornerstone of GIST treatment whenever resection is possible. Complete removal of a primary tumor is potentially curative, especially when the tumor is small and the risk classification is low (see Table 2 in Prognosis under About GIST). Although recurrence or metastasis is less likely for low-risk GISTs, all GISTs have malignant potential. If recurrence or metastasis does happen, it is usually within the first two years after surgery to remove a primary tumor. However, there are case reports of metastases appearing 10-20 years later. Therefore, long-term monitoring for recurrence is needed.
A number of papers in the medical literature describe patient outcomes after GIST surgery in the pre-imatinib era. However, these papers are difficult to interpret because most of them include some percentage of non-GIST cancers (such as leiomysarcoma) due to the fact that accurate GIST diagnosis became possible only after 1998, when KIT (CD117) expression by GISTs was discovered. In addition, these series tend to be from large cancer centers to which difficult cases are referred; therefore the series have a disproportionate number of high-risk patients and patients whose disease was already metastatic at diagnosis. These factors, plus the current availability of targeted molecular therapy if GIST does recur or metastacize, render the survival statistics from the pre-imatinib era less relevant today.
Recurrence rates for tumors of different sizes and mitotic rates, separated by tumor site, are available in a series of site-specific papers by Miettinen and colleagues at the Armed Forces Institute of Pathology. These papers are noteworthy because they contain very large series of cases broken down into prognostic categories, with follow-up information (Miettinen et al, 1999; Miettinen et al, 2000; Miettinen et al, 2001; Miettinen and Sobin, 2001; Miettinen et al, 2003; Miettinen et al, 2005, Miettinen et al, 2006).
Recent data from Sweden estimate the curative potential of surgery (Nilsson et al, 2005; Bumming et al, 2006). All KIT-positive GISTs in western Sweden from 1983-2000 were identified by re-examination of original pathology samples, producing a prospective population-based group of tumors. Of 259 clinical cases 199 were found due to patients’ symptoms, while 60 were discovered incidentally durin surgery for other conditions. In contrast to case series from referral centers, where perhaps half the cases are already metastatic, the Swedish data included only 14.6% (29 of 199) cases already metastatic at diagnosis. Excluding these and focusing on primary tumors, surgery was curative in over 97% of cases when complete resection could be achieved for patients whose risk group was very low, low, or intermediate (see Prognosis section Table 1). In the high-risk group, 48 of 60 patients achieved complete resection (80%). With a median of 8 years of followup post-surgery (range 1.8 to 19.5 years), 37.5% of high-risk patients with complete resection remained free of disease, while 62.5% developed recurrence or metastasis. Therefore, surgery does have curative potential even for higher-risk primary tumors.
Several excellent recent discussions of surgery for GIST in the targeted-therapy era are available: Scaife et al, 2003; Eisenberg and Judson, 2004; van der Zwan and DeMatteo, 2005; Heinrich and Corless, 2005; Neuhaus et al, 2005; Efron and Lillemoe, 2005, Barnes et al, 2005; the ESMO consensus guidelines published by Blay et al, 2005 (see summary slides on our site by Dr. Reichardt ); NCCN Sarcoma Guidelines, version 1.2007; Benjamin et al, 2006; Raut et al, 2006.
For many patients, surgery is scheduled on the basis of imaging results (ultrasound, CT, MRI. etc.) indicating the location of the tumor, but before the exact type of tumor has been diagnosed. Tumor biopsy prior to surgery is safe if it can be done endoscopically (as for gastric tumors). However, preoperative biopsy through the skin of the abdomen (percutaneous biopsy) is not recommended for operable tumors due to the small risk of seeding tumor cells along the biopsy path, plus the risk of tumor rupture into the abdomen. The exception is for inoperable tumors, when identifying the tumor type will affect treatment choices. If the biopsy of an inoperable tumor shows GIST, neo-adjuvant imatinib/Gleevec can be prescribed. For a discussion of biopsy issues, see the NCCN Sarcoma Guidelines and the opinion written by Dr. Christopher Corless for our website (Needle Biopsies).
Goals of surgery include:
- Complete removal of all tumor
- Clear surgical margins
- Avoidance of tumor rupture
Resection is usually segmental for all but the smallest tumors; this means an entire segment of the GI tract is removed (with the tumor attached to it) and the cut ends are reattached. Segmental resection contrasts with wedge (or peri-tumoral) resection, in which the GI tract area immediately around the tumor is removed (with the tumor attached to it) and the edges of the resulting hole are drawn back together. Several authors have reported a poorer prognosis after wedge/peri-tumoral resection than after segmental resection, apparently due to inadequate margins (Bucher, 2005, Aparicio, 2004). Laparoscopic surgery is generally not advised unless the GIST is smaller than 2 cm (NCCN, 2005).
Because GIST does not usually invade adjacent organs or structures, the tumor can often be lifted away from structures it has pressed against. However, if a GIST has adhered to adjacent structures and attempted dissection of the tumor from the normal organs poses a risk of tumor rupture, then an en bloc resection (removing the tumor along with portions of the structures it has adhered to as a single unit) may be required. Lymph node removal is not generally needed, as GIST very rarely spreads via the lymphatic system.
For patient-oriented tips on coping with surgery and a hospital stay, see Before You Go to the Hospital on our website.
Abdominal sarcoma surgery is not an everyday event at community hospitals. Surgeons at sarcoma centers will be much more familiar with and skilled in the resection of GISTs than general surgeons. The larger the GIST, the more important this may be to the patientâ€™s outcome. A tumor that is deemed inoperable by a general surgeon may well be resectable by an expert GIST surgeon. If the patient seeks the opinion of a sarcoma surgeon first, then the patient may save him or herself all the time, expense, and extended recovery from an attempted surgery that turns out to be deemed â€œexploratoryâ€ when the general surgeon opens the abdomen only to decide that the GIST appears too difficult to resect.
Surgical case histories h
ave been published recently describing how shrinkage of a poorly situated GIST via imatinib (Gleevec) therapy can either render a previously inoperable tumor resectable, or reduce the scope of resection by avoiding potentially debilitating sacrifice of normal organs (Wu et al, 2003; Heinrich and Corless, 2005; Lo et al, 2005; Loughrey et al, 2005; Shah et al, 2005; Neuhaus et al, 2005). There is also a neoadjuvant trial sponsored by the Radiation Therapy Oncology Group in which patients receive two months of imatinib prior to surgery and two years of imatinib post-surgery (RTOG S0132). In a series of 33 patients who took neo-adjuvant imatinib, Hohenberger et al (2009 ASCO abstract 10550) found that 5 of 6 previously inoperable patients became operable, and 21 of 25 other patients were able to have their GISTs removed by a less extensive surgical procedure.
Aparicio T, Boige V, Sabourin JC, Crenn P, Ducreux M, Le Cesne A, Bonvalot S.
Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours.
Eur J Surg Oncol. 2004 Dec;30(10):1098-103. PMID: 15522557
Barnes G, Bulusu VR, Hardwicj RH, Carroll N, Hatcher H, Earl HM, Save VE, Balan K, Jamieson NV.
Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib.
International Journal of Surgery 2005; 3:206-212. Not indexed in PubMed.
Bauer S, Hartmann JT, de Wit M, Lang H, Grabellus F, Antoch G, Niebel W, Erhard J, Ebeling P, Zeth M, Taeger G, Seeber S, Flasshove M, Schutte J.
Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib.
Int J Cancer. 2005 Nov 1;117(2):316-25. PMID: 15900603
Benjamin RS, Blanke CD, Blay JY, Bonvalot S, Eisenberg B.
Management of gastrointestinal stromal tumors in the imatinib era: selected case studies.
Oncologist. 2006 Jan;11(1):9-20. PMID: 16401709
Blay JY, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, Emile JF, Gronchi A, Hogendoorn PC, Joensuu H, Le Cesne A, McClure J, Maurel J, Nupponen N, Ray-Coquard I, Reichardt P, Sciot R, Stroobants S, van Glabbeke M, van Oosterom A, Demetri GD; GIST consensus meeting panelists.
Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO.
Ann Oncol. 2005 Apr;16(4):566-78. PMID: 15781488
Bucher P, Egger JF, Gervaz P, Ris F, Weintraub D, Villiger P, Buhler LH, Morel P.
An audit of surgical management of gastrointestinal stromal tumours (GIST).
Eur J Surg Oncol. 2006 Apr;32(3):310-4. PMID: 16414236
Bumming P, Ahlman H, Andersson J, Meis-Kindblom JM, Kindblom LG, Nilsson B.
Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours.
Br J Surg. 2006 Jul;93(7):836-43. PMID: 16705644
Efron DT, Lillemoe KD.
The current management of gastrointestinal stromal tumors.
Adv Surg. 2005;39:193-221. PMID: 16250553
Eisenberg BL, Judson I.
Surgery and imatinib in the management of GIST: emerging approaches to adjuvant and neoadjuvant therapy.
Ann Surg Oncol. 2004 May;11(5):465-75. PMID: 15123459
Gold JS and DeMatteo RP.
Combined Surgical and Molecular Therapy: The Gastrointestinal Stromal Tumor Model.
Ann Surg. 2006 August; 244(2): 176â€”184. free access through PubMed – click title to link.
Heinrich MC, Corless CL.
Gastric GI stromal tumors (GISTs): the role of surgery in the era of targeted therapy.
J Surg Oncol. 2005 Jun 1;90(3):195-207; discussion 207. PMID: 15895440
Lo SS, Papachristou GI, Finkelstein SD, Conroy WP, Schraut WH, Ramanathan RK.
Neoadjuvant imatinib in gastrointestinal stromal tumor of the rectum: report of a case.
Dis Colon Rectum. 2005 Jun;48(6):1316-9. PMID: 15793646
Loughrey MB, Mitchell C, Mann GB, Michael M, Waring PM.
Gastrointestinal stromal tumour treated with neoadjuvant imatinib.
J Clin Pathol. 2005 Jul;58(7):779-81. PMID: 15976351
Miettinen M, Makhlouf H, Sobin LH, Lasota J.
Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up.
Am J Surg Pathol. 2006 Apr;30(4):477-89.
Miettinen M, Sobin LH, Lasota J.
Gastrointestinal stromal tumors of the stomach: a clinicopathologic,immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up.
Am J Surg Pathol. 2005 Jan;29(1):52-68. PMID: 15613856
Miettinen M, Kopczynski J, Makhlouf HR, Sarlomo-Rikala M, Gyorffy H, Burke A, Sobin LH, Lasota J.
Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases.
Am J Surg Pathol. 2003 May;27(5):625-41. PMID: 12717247
Miettinen M, Sobin LH.
Gastrointestinal stromal tumors in the appendix: a clinicopathologic and immunohistochemical study of four cases.
Am J Surg Pathol. 2001 Nov;25(11):1433-7. PMID: 11684962
Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J.
Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases.
Am J Surg Pathol. 2001 Sep;25(9):1121-33. PMID: 11688571
Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J.
Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas.
Am J Surg Pathol. 2000 Feb;24(2):211-22. PMID: 10680889
Miettinen M, Monihan JM, Sarlomo-Rikala M, Kovatich AJ, Carr NJ, Emory TS, Sobin LH.
Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases.
Am J Surg Pathol. 1999 Sep;23(9):1109-18. PMID: 10478672
NCCN, National Comprehensive Cancer Network.
Soft Tissue Sarcoma Guidelines version 2.2006
Neuhaus SJ, Clark MA, Hayes AJ, Thomas JM, Judson I.
Surgery for gastrointestinal stromal tumour in the post-imatinib era.
ANZ J Surg. 2005 Mar;75(3):165-72. PMID: 15777399
Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG.
Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era–a population-based study in western Sweden.
Cancer. 2005 Feb 15;103(4):821-9. PMID: 15648083
Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, Fletcher CD, Demetri GD, Bertagnolli MM.
Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors.
J Clin Oncol. 2006 May 20;24(15):2325-31.
Raut CP, Desai J, Morgan JA, George S, Posner M, Zahrieh D, Fletcher CDM, Demetri GD, Bertagnolli MM.
Surgical management of advanced GIST following KIT-directed therapy.
Slide show from presentation at 2005 meeting of Connective Tissue Oncology Society.
Scaife CL, Hunt KK, Patel SR, Benjamin RS, Burgess MA, Chen LL, Trent J, Raymond AK, Cormier JN, Pisters PW, Pollock RE, Feig BW.
Is there a role for surgery in patients with “unresectable” cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate?
Am J Surg. 2003 Dec;186(6):665-9. PMID: 14672776
Shah JN, Sun W, Seethala RR, Livolsi VA, Fry RD, Ginsberg GG.
Neoadjuvant therapy with imatinib mesylate for locally advanced GI stromal tumor.
Gastrointest Endosc. 2005 Apr;61(4):625-7. PMID: 15812427
van der Zwan SM, DeMatteo RP.
Gastrointestinal stromal tumor: 5 years later.
Cancer. 2005 Nov 1;104(9):1781-8. PMID: 16136600
Wu PC, Langerman A, Ryan CW, Hart J, Swiger S, Posner MC.
Surgical treatment of gastrointestinal stromal tumors in the imatinib (STI-571) era.
Surgery. 2003 Oct;134(4):656-65; discussion 665-6.