Treatment of choice for DLBCL irrespective of anatomic site of the lesion is rituximab plus anthracycline-based combination chemotherapy: epirubicin, or adriamycin or mitoxantrone combined with cyclophosphamide, vincristine and prednisone (CHOP, CEOP or CNOP regimen). Although the impact of the addition of rituximab to chemotherapy regimens has not been tested in large clinical trials in patients with PG-DLBCL [59
], treatment must include rituximab due to its proven therapeutic benefit in DLBCL [60
]. Complications of chemotherapy include gastric outlet obstruction and bleeding while gastric perforation is rare. Therefore, irrespective of the role of gastrectomy as primary treatment of patients with DLBCL of the stomach which as explained below remains controversial, the role of surgical consultant remains essential in the management of DLBCL of the stomach.
The role of surgery in the management of PG-DLBCL is controversial. Many previous studies have suggested that gastrectomy, particularly in stages I and II patients, significantly improves survival [62
]. In addition, complications such as perforation, obstruction and hemorrhage can be prevented or treated with surgery. However, these complications are rare. Several studies have shown that patients undergoing gastrectomy have a better outcome compared with those having incomplete resection or biopsy alone [66
]. It is unclear, however, whether the improved outcome is related to low tumor burden which allows complete resection, similarly to low LDH, or the surgery itself. Contrary to the aforementioned reports, other studies have shown that the extent of surgery (excision or biopsy) has no impact on outcome of GI lymphomas [3
]. The excellent results obtained with the use of combination chemotherapy, sometimes combined with radiation, have challenged the role of gastrectomy in the management of patients with PG-DLBCL [71
]. Some retrospective and prospective studies suggested that conservative nonsurgical treatment achieves equal or better results than gastrectomy (reviewed recently by Ferreri and Montalban [73
]). In our study, patients treated with surgery plus chemotherapy had similar OS and disease-free survival after 38 months of median follow-up with patients treated with chemotherapy alone [5
]. In addition, a small prospective randomized trial comparing patients with PG-DLBCL treated with combination chemotherapy alone or with surgical resection followed by chemotherapy concluded that gastrectomy is unnecessary (10-year survival rates 96% and 91%, respectively) [74
]. However, the question is open and further prospective trials are required to determine the optimal management of this disease.
The role of consolidation radiotherapy is debated. In retrospective studies, the addition of RT was associated with a lower local relapse rate compared with chemotherapy alone [75
]. In a prospective study, the combination of six cycles of CHOP-14 followed by involved-field RT (40 Gy) has been associated with a survival rate at 42 months of 91% [76
]. Further prospective randomized trials are required in order to answer the question about the role of RT in the treatment of PG-DLBCL.
In addition to chemotherapy, H. pylori
eradication with antibiotic therapy should always be carried out in localized or extensive PG-DLBCL, especially in cases of PG-DLBCL with concomitant low-grade MALT component [77
]. Although PG-DLBCL with MALT component appeared to be independent of the H. Pylori
antigen drive, two recent studies showed that 60% of patients with PG-DLBCL with MALT areas achieved histological CR after H. Pylori
eradication, which have been maintained after long follow-up [78
The choice of treatment for patients with relapsed or refractory disease depends on patient's age, performance status, extension of relapse and previous therapies. At present, high-dose therapy followed by autologous stem-cell transplantation is the treatment of choice for patients in whom chemosensitivity to some kind of salvage treatment is still present. However, only young patients with good performance status and without comorbidities are candidates for this therapy. Gastrectomy can be a suitable approach in elderly patients who experience relapse limited to the gastric wall and exhibit clear contraindications to chemotherapy. Finally, new combinations of chemotherapeutic regimens, immunotherapy and radioimmunotherapy should be tested in prospective phase II trials on patients with relapsed or refractory PG-DLBCL.