Current best practices and rationalistic perspectives in causation-based prevention, early detection and multidisciplinary treatment of breast and gastric cancer


Volume 1- Number 2 -October/December 2002

 

EDITORIAL

Time to Move on From Current Strategy in Gastric Cancer?

Dimitrios H. Roukos, MD
From the Department of Surgery, Ioannina University School of Medicine, 45110 Ioannina, Greece,
droukos@cc.uoi.gr


Adenocarcinoma of the stomach with approximately 700,000 to 800,000 new cases per year worldwide is a major health problem. Despite its declining incidence it remains the second leading cause of cancer-related deaths. The decrease in incidence varies considerably among continents and countries; slow in Asia and developing countries and rapid in the western world. In the USA only 21,600 new cases are expected in 2002 [1: www.cancer.org], but the sharply declining incidence-curve in the last five decades shows now a trend toward a stabilization.[1] By contrast, incidence in Japan with about 50 new male cases each year per 100,000 population, vs. only 8.7 in the USA, remains one of the highest in the world.

Progress against cancer is assessed primarily by the reduction of mortality over time. Reduction in deaths from gastric cancer may resulted from: (a) decrease in incidence, (b) increase of the early detection and the proportion of early-stage cancers which have a good prognosis (c) better treatment in all stages-cancer reflected by higher survival rates in each stage cancer, and (d) combinations of them. Improvements in treatment-related morbidity and quality of life (QOL) should also be considered in the assessment of a possible progress.

Time trends results therefore separately evaluated according to the cause of improvement are the gold standard in order to be precisely assess the reasons for a possible improvement. Strategies against cancer include prevention for decreasing the incidence, screening for increasing the early detection and appropriate treatment for better survival. Assessing therefore the strategies that have lead to more effective outcomes in both survival and QOL we could design the best strategy. Public health efforts and funding should be focused on an intervention strategy that will provide the most promising findings for future implications.

Evaluating and comparing gastric cancer time trends results between USA and Japan -because of different reasons of decreasing mortality - we can draw conclusions of how the struggle against gastric cancer could be achieved more effectively. In the USA, mortality has been dramatically reduced during the last decades and only 12,400 deaths from gastric cancer are expected in 2002.[1] Time trends results indicate that the fall in cancer deaths in the USA is attributable largely to the decreased incidence because both early detection and survival at 5 years after treatment have been slightly improved. Surgical resection is curative in less than 40% [2] of cases and overall 5-year survival rate remains at only 22%.[1] The reasons for the sharply declining incidence are unclear. Possible explanations include a better refrigeration, availability and consumption of fresh fruits, decreased consumption of salty foods and decrease in incidence of Helicobacter pylori infection, which is a causative risk factor of gastric carcinogenesis. Noteworthy, this decrease is not attributable to systematic public health efforts but rather to accidental events.

Limitations of current treatment

Surgery remains the treatment of choice and the only treatment modality able to prolong survival or to provide cure, but only when the disease is localized. Indeed, survival data has proved that surgery is effective only when it results in a complete removal of both the primary tumor and of the affected lymph nodes -curative or R0 resection.

Unfortunately, this prerequisite concerns only 40%[2] to 70%[3] of all cases in the West. For the remaining 30-60% of patients with a non-curatively resected tumor or with metastatic disease, prognosis is extremely. But even after curative resection, fatal relapse at local or distant sites is frequent in a stage-depended manner -lower in early stage-cancers, higher in advanced stage-cancers.

Recurrence rate after adequate curative surgery is low, about 10%[4] when the disease is confined to the stomach wall without involvement of serosa or lymph nodes [T1-2,N0], but high in more advanced stages reaching in up to 85%[4] of patients with both serosa and node positive-cancer.

Worldwide, the most substantial progress against gastric cancer has been occurred in Japan, a country with very high incidence rates. Deaths have been reduced about 50% within 4 years; 49,739 people died of gastric cancer in 1997, but the estimated number of cases in 1994 was 97,991.[5] This fall of deaths from gastric cancer is attributable to an increase of early detection through screening and appropriate standardized surgical (D2) technique. Resection is curative in over 80% and 5-year survival rate is about 50% to 60%.[6] The results underscore the power of screening and early detection.[5]

After surgery, adjuvant treatment with chemotherapy, radiotherapy or both is routinely used worldwil de. But the effectiveness of adjuvant treatment to prolong survival either after curative or noncurative surgery remains controversial.[2,3,7,8] In the western world therefore, it is not surprising that overall 5-year survival rate now remains low, approximately 22% in the U.S. without substantial increase during the last decades.[1] Promises for progress indicate some recent results from European countries with overall 5-year survival rates over 30%, or 40%-50% after curative surgery.[9-11] This survival improvement is likely attributable to an increase of early detection[9,10] and/or use of D2 node dissection as standard surgical treatment.[9,11]

New combined treatments with intra-, or post-operative adjuvant treatment and essential pre-treatment sophisticated staging procedures are under active prospective investigation, but they are too expensive and the survival benefit expected is rather low.

Particularly in developing countries these multidisciplinary cancer therapeutics are completely unrealistic to be applied even in the distant future. The problem in controlling gastric cancer in Asia and developing countries will remain substantial in the next decades, because incidence decreases slowly in these countries, which will experience the greatest world's population growth from the current 6.1 billion to 9.3 billion during the next 50 years (United Nations' Population Division).

Prevention of gastric cancer is increasingly receiving attention as an intervention strategy with potential power to reduce massively the incidence of the disease.

Promising are the findings with H. pylori eradication and/or vitamin supplementation by a recent chemoprevention randomized trial[12] but still inconclusive.

Up until now most public health interest and funding of research has been focused on the development of multidisciplinary cancer therapeutics of clinically detected gastric cancer. But the benefit of such a strategy is rather small if one considers the billions of dollars which have been spent for a slight survival improvement. Early detection and (chemo)-prevention providing promising findings for an improvement of both survival and quality of life, strongly indicate the need for increased attention and funding of research towards development of strategies that will increase detection of the disease at early stages and will reduce the incidence due primary prevention.

References
1.Jemal A, Thomas A, Murray T, Thun M. Cancer Statistics, 2002. CA Cancer J Clin 2002; 52(1):23-47.
2.Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001; 345: 725-30.
3.Roukos DH, Fatouros M, Xeropotamos N, Kappas AM. Treatment of gastric cancer: early-stage, advanced-stage cancer, adjuvant treatment. Gastric Breast Cancer 2002; 1(1): 12-22.
4.Lorenz M, Roukos DH, Karakostas K, Hottenrott C, Encke A. Accurate prediction of site-specific risk of recurrence after curative surgery for gastric cancer. Gastric Breast Cancer 2002; 1(2): 23-32
5.Sano T, Sasako M. Green tea and gastric cancer. N Engl J Med 2001 ; 344 : 675-6.
6.Fujii M, Sasaki J, Nakajima T. State of the art in the treatment of gastric cancer: from the 71st Japanese gastric cancer congress. Gastric Cancer 1999; 2:151-7
7.Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, Goto M and the Gastric Cancer Surgical Study Group. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomized trial. Lancet 1999;354:273-7.
8.Sun W, Haller DG. Recent advances in the treatment of gastric cancer. Drugs 2001;61(11):1545-51
9.Siewert JR, Boettcher K, Stein HJ, et al. Relevant prognostic factors in gastric cancer. Ten-year results of the German Gastric cancer Study. Ann Surg 1998; 228: 449-461.
10.Bonnenkamp JJ, Hermans J, Sasako M, van de Velde CJH, et al. Extended lymph-node dissection for gastric cancer. N Engl J Med 1999; 340: 908-14.
11.Roukos DH. Optimising lymph lode dissection for gastric cancer. Gastric Breast Cancer 2002; 1(2): 40-43.
12.Correa P, Fontham ETH, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidants supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst 2000; 92: 1881-8.

Online ISSN : 1109 - 7647
   Print ISSN : 1109 - 7655

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last update: 22 May 2003