Adjuvant therapy after primary surgery for stage I-IIA carcinoma of the cervix

Radical hysterectomy and bilateral pelvic lymph node dissection is commonly used as a primary management option for treatment of stage IB/IIA carcinoma of the cervix. Overall cure rates approach 85%. However, a spectrum of relapse risk exists, depending on the presence or absence of primary tumor and nodal-related prognostic factors. Known factors include number and location of lymph nodes; size of primary, deep invasion in the cervix; capillary lymphatic space involvement; occult parametrial involvement; and positive or close surgical margins. Biologic determinants have yet to be identified. No systematic analysis has examined various combinations of prognostic factors to precisely define associated levels of risk and to predict the sites of relapse. Decreased local control and survival rates in some high-risk subgroups, usually those with nodal positivity, has led to the exploration of adjuvant therapies. Compiled data from retrospective series have defined the overall patterns of failure. Seventy-two percent of those relapsing have a component of pelvic failure, while 42% experience relapse in the pelvis alone. Fifty-eight percent have a component of distant failure but only 28% have distant disease alone. Adjuvant treatment options include pelvic radiotherapy, extended-field radiotherapy, chemoradiotherapy, and chemotherapy. Trials of adjuvant chemotherapy are too few to evaluate the use of available agents. Pelvic radiotherapy has been shown to reduce the relapse risk when surgical margins are close or positive. It also reduces the risk of pelvic relapse and improves the relapse-free interval but has no apparent impact on overall survival in the groups that have been selected for treatment. The apparent lack of benefit may relate to the choice of patients with nodal involvement who, despite high risk of pelvic failure, most likely have a predominant pattern of distant failure. Maximization of the survival benefit of pelvic radiotherapy requires the identification and treatment of the subgroup with a predominant pattern of pelvic failure, such as that examined in Gynecologic Oncology Group protocol 92. These may be patients with primary tumor-related, high-risk factors but negative nodes. Extended-field irradiation for microscopically involved para-aortic nodes provides a cure in 25%-40% of the patients. Further studies of prognostic factors and their relationship to sites of failure after surgery are necessary to define the benefits of currently available adjuvant therapies with respect to local control, survival, and quality of life, and also to direct future studies. New, effective systemic agents are required for those at high risk of developing distant disease.     

Improving the treatment of colorectal cancer: the role of EUS

The two most important factors for determining the risk of local failure and overall prognosis in colorectal carcinoma are nodal status and the depth of tumor penetration into or through the bowel wall. These features have traditionally been determined pathologically because the clinical-staging accuracy of other imaging modalities such as computed tomography (CT) has not proven sufficiently predictive of surgical staging. However, endorectal or endoscopic ultrasonography (EUS) can be used to preoperatively evaluate nodal involvement with an accuracy of up to 86% (median: 80%) and depth of tumor penetration through the bowel wall with an accuracy of up to 97% (median: 85%) for effective clinical staging. This high staging accuracy is useful in managing colorectal cancer. Through clinical evaluation of the initial stage of colorectal cancer with EUS, a patient's risk of disease recurrence can best be determined and patients stratified for the most appropriate treatment. EUS can be used to select patients with lesions that can be treated with local excision or sphincter-sparing surgery, often combined with radiation therapy, in situations otherwise requiring an abdominoperineal resection. EUS can also be used to preoperatively identify patients with locally advanced or unresectable disease. Chemoradiation can then be given preoperatively, when it appears to be better tolerated and more effective than postoperative treatment. Unresectable tumors can often be downstaged sufficiently to allow their excision. In resectable disease, EUS can also identify patients at high risk for recurrence who would benefit from adjuvant chemoirradiation. EUS for precise staging or for earlier diagnosis of recurrence will further improve the clinical outcome of patients with colorectal tumors as significant advances both in surgical techniques and in combined chemotherapy/radiotherapy continue to be made and applied selectively in a stage-dependent manner.     

A phase II trial and pharmacokinetic analysis of 96-hour infusional paclitaxel in patients with metastatic colorectal cancer

AIMS: To carry out a retrospective study of male breast cancer over a 22-year experience. METHODS: Data from 121 male patients with breast cancer treated between the years 1972 and 1994 at the Surgical Clinic of Ankara Oncology Hospital were reviewed. Distribution of cases according to stage was: 2.5% stage I, 28.9% stage II, 55.4% stage III and 13.2% stage IV (AJCC staging method). The surgical treatment for 23 of the patients (19%) was Halsted's radical mastectomy or modified radical mastectomy. Seventy-three cases (60.3%) had total mastectomy without axillary node dissection and 25 (20.7%) had local tumour excision only. Seventy-two of 121 patients had adjuvant treatment. RESULTS: In general the prognosis of men with breast cancer was worse than for women. In the analysis of patients in stages I, II and III-A (operable disease group), the 5-year survival rates were 73% in axillary node-negative patients and 77% in those with tumours sized under 5 cm (P<0.001). In these patients, univariate analysis demonstrated that axillary status (relative risk of death in positive status vs. negative=3.6), tumour size (relative risk in T3 vs. T1-2=2), surgical treatment type (relative risk in simple mastectomy vs. radical mastectomy=1.9) and adjuvant chemotherapy (relative risk if no chemotherapy=1.4) were statistically significant factors associated with survival. CONCLUSIONS: Cox's regression model revealed that axillary status, tumour size and type of surgical treatment were the most important independent prognostic factors (P<0.001).     

Metachronous liver metastasis of colorectal cancer: timing of occurrence and efficacy of adjuvant portal chemotherapy

We estimated the time of occurrence of metachronous liver metastasis in colorectal cancer patients from tumor diameter and doubling time. Micro-metastasis was present prior to operation in most patients and a few metastatic cases could have been initiated by the surgical procedure. Portal chemotherapy is more effective against liver metastasis than intravenous infusion because a higher drug concentration in the liver can be obtained. This efficacy of portal chemotherapy on survival was also observed in a rat model. Thus perioperative adjuvant treatment should be undertaken for metastasis which already existed before the operation and adjuvant chemotherapy via portal vein is the treatment of choice. The no touch isolation technique is also needed to avoid spreading of tumor cells during surgery.     

Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.     

Resection of hepatic metastases from colorectal cancer

BACKGROUND/AIMS: Long term results of hepatic resection for metastases from colorectal cancer depend upon several factors which are related to both features of primary cancer and of metastases. The aim of this study was to evaluate prognostic factors that best correlate with long-term results. MATERIALS AND METHODS: Fifty-eight hepatic resections were performed for colorectal cancer metastases. Long-term results were evaluated in relation to age of patients, features of primary tumor, features of metastases, section margin, number of intra-operative blood transfusions and execution of adjuvant chemotherapy. RESULTS: Overall 5-year survival rate was 17%. 5-year survival rate in patients with stage B primary tumor was 63%, in patients with late metachronous metastases it was 28%, in patients with section margin > 1 cm it was 33% and in patients who did not receive intra-operative transfusions it was 45%. Patients with a solitary metastasis or with metastases sized less than 4 cm and those who received adjuvant chemotherapy also showed a better survival than the others. CONCLUSIONS: Better results were observed in patients without nodal involvement of the primary tumor. Patients with a small solitary metachronous metastasis that appeared more than one year after the colorectal resection and resected with a section margin of more than 1 cm, also showed good results.     

The case for high-dose adjuvant chemotherapy in breast cancer: (I) theoretical considerations

Adjuvant systemic therapy of breast cancer is now a well-established treatment resulting in improved survival. However, the available evidence suggests that it is most unlikely that an individual woman will be cured as a consequence of such treatment. There is, therefore, a pressing need for more effective therapy, particularly for younger women whose degree of axillary nodal involvement indicates a high risk of subsequent relapse. The case for using myelo-ablative chemotherapy for such women is presented in this article. In a subsequent publication we will discuss the clinical data to suggest that such an approach is not only possible with acceptable toxicity, but also could actually offer the increased cure rate sought by clinicians and patients alike.     

Role of adjuvant chemotherapy in the treatment of invasive carcinoma of the urinary bladder

PURPOSE: The standard treatment for patients with muscle-invasive carcinoma of the urinary bladder is radical cystectomy. While radical cystectomy cures many patients with this tumor, almost 50% of them will develop metastatic disease. Adjuvant chemotherapy has been proposed for these patients in an attempt to reduce the probability of relapse and to improve survival. To assess whether adjuvant chemotherapy does benefit patients with muscle-invasive bladder cancer, we reviewed all phase II and III studies published in the English literature over the last 20 years. METHODS: A review of all published reports was facilitated by the use of Medline computer search and by manual search of the Index Medicus. RESULTS: Several comparative, nonrandomized studies have indicated that adjuvant chemotherapy may prolong disease-free survival. Four randomized studies have been conducted and all had a suboptimal patient accrual. Three studies used a cisplatin-containing combination chemotherapy and included primarily patients with non-organ-confined transitional-cell carcinoma (TCC) of the bladder. All three studies indicated that adjuvant chemotherapy improved disease-free survival and two of them also showed improvement in event-free survival and overall survival, respectively. CONCLUSION: Published series have been unable to establish an undisputed benefit of adjuvant chemotherapy over radical cystectomy alone for muscle-invasive bladder cancer. The interpretation of the available data is compromised by several methodologic and statistical problems. Thus, adjuvant chemotherapy cannot be considered as a standard treatment for all patients with muscle-invasive carcinoma of the bladder. Well-designed prospective randomized studies are needed to clarify the role of adjuvant chemotherapy in this disease. However, outside a protocol setting, there is some evidence that patients with extravesical disease or with lymph node involvement may benefit from adjuvant treatment with cisplatin-based combination chemotherapy. No data support such an approach for patients with muscle-invasive but organ-confined bladder cancer.     

Treatment of breast cancer]

EPIDEMIOLOGY IN FRANCE: Breast cancer causes 11,000 deaths annually in France and 25,000 new cases are diagnosed each year. Currently, the overall survival rate is 73% at 5 years and 59% at 10 years. Treatment and outcome depend largely on stage at diagnosis and metastatic extension, but many questions remain open. NON-METASTATIC BREAST CANCER: Breast conserving tumorectomy with nodal dissection and radiation therapy is the rule for small tumors measuring less than 3 cm, although there is still some debate on safety margins and the appropriate attitude in case of invasion. Likewise, there are arguments both for and against primary chemotherapy before tumorectomy. Currently, primary chemotherapy should be given in all cases of inflammatory cancers and preferentially for large tumors. Nodal dissection is essentially a diagnostic procedure and is almost always performed although trials evaluating the value of the sentinel node may have an effect on current attitudes. Despite recent advances in adjuvant therapy, dose and combination of chemotherapy are still open questions. There is however a consensus that chemotherapy should be prescribed for all premenopausal patients with node negative and adverse prognosticators and for all patients under 70 with nodal invasion associated with hormonotherapy after menopause if hormone receptors are positive. METASTATIC BREAST CANCER: At this stage, remission together with quality of life are the primary treatment goals. The best response rates (around 65%) are obtained with polychemotherapy protocols including anthracyclins and complete remission can be obtained in approximately 15% of the patients. There is some hope that chemoresistance may be curtailed with new agents such as vinorelbin or the taxane family. High-dose chemotherapy with hematopoietic rescue is another avenue of research aimed at reducing chemoresistance and improving survival. Overall response to hormone therapy is around 30%. Response rate peaks near 70% in cases positive for estrogen and progesterone receptors, but falls to only 10% if hormone receptors are absent. The role of new hormone therapies using new antiestrogen and antiaromatic compounds remains to be determined. AN ONGOING CHALLENGE: Mortality due to breast cancer has started to decline in developed countries despite increasing incidence. This reduction is undoubtedly related to advances in hormone therapy and adjuvant chemotherapy but also to screening programs and early diagnosis. In the Scandinavian countries, it has been demonstrated that mortality can be reduced to the order of 30 to 40% with mass screening, a challenge which should be met in France.     

Extended radical pancreatectomy for carcinoma of the head of the pancreas

BACKGROUND/AIMS: Pancreatic cancer has a poor prognosis, which is, in part due, to the unfortunately advanced stage, in which the tumor is diagnosed. Since 1973, we have utilized a unique method of extended radical pancreatectomy, using the translateral retroperitoneal approach (TRA) to facilitate combined portal resection. The advantages of this operation are described herein, for patients with carcinoma of the head of the pancreas. In addition, the problems associated with this operation are discussed. METHODOLOGY: Survival was calculated based on type of resection, degree of invasion of the retroperitoneal tissues, degree of lymph node involvement, and cancer stage. Extensive surgery has been performed for pancreatic carcinoma 216 patients. Of these, 14 patients had carcinoma of the head of the pancreas. There were 58 patients who underwent macroscopically curative resections. RESULTS: Only 39 patients were microscopically curative. Ten of the patients who underwent microscopically curative resections, survived for 5 years (34.0%). There were no statistically significant differences in survival based on tumor size. However, there was a significant difference in survival based on extent of invasion of the anterior capsule of the pancreas, extent of invasion of the retroperitoneal tissue, extent of lymph node involvement, cancer stage, and extent of invasion at the surgical margin of resection. CONCLUSION: The results suggest that extended radical pancreatectomy may be indicated for the treatment of cancer of the head of the pancreas.     

Adjuvant therapy of colorectal carcinoma--1998 status]

Colorectal cancer is the second leading cause of cancer death in western countries. The prognosis is strongly correlated to the TNM-staging system and patients with stage T3-4 and/or node positive disease are at high risk for locoregional or distant relapse. It is now widely accepted that patients with node positive colon cancer should be offered postoperative adjuvant chemotherapy. Evidence is accumulating that six months' adjuvant fluorouracil plus leucovorin is equivalent to twelve months' fluorouracil and levamisole, which reduces cancer related deaths by more than 30%. Other adjuvant treatment approaches are perioperative regional chemotherapy or monoclonal antibody treatment, and the results of trials comparing these different treatment options alone or in combination are eagerly awaited. In rectal cancer, the risk of locoregional recurrence can be more than 50% and this event is associated with a deterimental effect on quality of life. The technique of mesorectal excision and the use of radiotherapy, alone or in combination with chemotherapy, have evolved as the most important measures for prevention of locoregional recurrence. In addition, chemotherapy has proven to be effective in reducing metastatic relapse and prolonging survival. The timing of radiotherapy (pre- versus postoperative) and the optimal combination of chemotherapy with radiation are presently important research issues in resected rectal cancer. In both colon and rectal cancer, a common theme emerging from the experience of the last few decades is that administration of dose-intensive fluorouracil is key for the success of adjuvant treatment.     

Long-term results following resection for T3 non-small cell lung cancer

Surgical intervention is routinely employed for non-small cell lung cancer, whenever no distant metastasis is found. However, its surgical results depend on the staging of the lung cancer, and surgery for stage III disease is less effective compared with stage I or II disease. For patients with stage III, some treatments such as induction chemotherapy have been tried to support the surgery. Recently, T3 lung cancer is divided in two category of staging, T3N0 is evaluated to be stage II B and T3N1-2 is stage III A. In this study, we classified T3 diseases by some factors, and examined long-term survival of each group. As a result, we concluded that mediastinal invasion and N2 involvement were risk factors to early failure. On the contrary, patients with adjacent lobe invasion and resection of two lobes led to the prolonged survival rather than lobectomy with partial resection of adjacent lobe.     

ERCC1对胃癌患者手术及化疗后生存预测的意义

Objective:The aim of this study was to evaluate the effect of the excision repair cross-complementing (ERCC1) expression on survival in advanced gastric cancer patients who underwent surgical resection and treated with oxaliplatin-based adjuvant chemotherapy. Methods: Sixty-three patients who underwent surgical resection for cure and treated with oxaliplatin-based adjuvant chemotherapy were included in this study. The expressions of ERCC1 of gastric cancer were examined by immunohistochemistry and the patients were categorized into ERCC1-(+) and ERCC1-(-) groups. The relation between ERCC1 expression and survival of patients was examined. Results: Of the 63 eligible patients, 36 patients (57.1%) had tumor with a positive expression of ERCC1 and the remaining 27 patients had tumor with a negative ERCC1 expression. Expression differences of ERCC1 didn't correlated with age (P - 0.827), gender (P = 0.12), differentiation (P = 0.113), historical type (P = 0.942), site of tumor (P = 0.221), size of tumor (P = 0.608), stage (P = 0.815) and lymphatic invasion (P = 0.165). Overall survival (OS) was significantly longer in patients without ERCC1 expression, when compared to patients with ERCC1 expression (P = 0.023). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (MR: 4.049; P = 0.000). Conclusion: We concluded that resected and treated with oxaliplatin-based adjuvant chemotherapy gastric cancer patients without ERCC1 expression have a better survival when compared to patients with ERCC1 expression. ERCC1 expression will hopefully provide a rational basis for improving adjuvant chemotherapeutic strategies for gastric cancer patients. ERCC1, itself, may be a prognostic factor for gastric cancer.     

Proposal of a risk score for recurrence in patients with curatively resected gastric cancer

In this study, 168 patients who underwent curative resection for gastric cancer with prognostic serosal invasion [ps(+)] and 150 without prognostic serosal invasion [ps(-)] were analyzed separately to determine the prognostic importance of clinicopathological factors, and identify which patients were at high risk of recurrence. A multivariate analysis of survival time using Cox's proportional hazard model revealed the important prognostic factors to be: Lymph node involvement, the classification of gross appearance, macroscopic serosal invasion, and interstitial connective tissue in the ps(+) group; and lymph node involvement, macroscopic serosal invasion, and venous invasion in the ps(-) group. We proposed a risk score of recurrence based on the results of a further multivariate analysis called Hayashi's Quantification Analysis II, in which recurrence was chosen as an objective variable and the above prognostic factors were chosen as explanatory variables. Eighty-four percent of the patients with a score of 0 or higher in the ps(+) group and 83% of those with a score of +6 or higher in the ps(-) group showed recurrence. Thus, we believe that this score is useful for identifying those patients at high risk of recurrence, who should receive intensive chemotherapy even after curative resection.     

Effect of UFT on treatment of urological cancer--effect of UFT on treatment of invasive bladder cancer and advanced prostate cancer. Ibaraki Urological Cancer Chemotherapy Study Group

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.     

Adjuvant medical therapy for colorectal cancer

In the mid-1980s, trials of adjuvant therapy for colon cancer in the United States had a "no treatment" arm, which reflected the belief that effective adjuvant chemotherapy did not exist for patients with surgically resected disease at high risk for recurrence. However, with the observation in the early 1990s that postsurgical adjuvant 5-FU plus levamisole reduced tumor recurrence and ultimately increased overall survival in stage III colon cancer, the potential of effective adjuvant chemotherapy was realized. Questions about the duration of adjuvant chemotherapy, the specifics of chemotherapy schedule/drug selection, and its use in stage II colon cancer are beginning to be clarified in large, randomized adjuvant therapy trials. In rectal carcinomas, combined modality postoperative pelvic irradiation plus chemotherapy for stage II and III disease has been shown to reduce both local and systemic recurrences and to prolong survival compared with that in patients treated with local surgery and radiation. Again, large randomized trials are attempting to clarify both the optimal chemotherapeutic agents and schedules to be used and also whether preoperative combined modality therapy can improve the resectability rate, rate of sphincter preservation, and survival. Future trials will examine new agents shown to be effective in advanced disease as well as monoclonal antibodies, such as MoAb 17-1A, that may have selective activity in minimal disease. Improvement in overall survival remains the ultimate endpoint of future adjuvant therapy trials; however, trials will also critically examine toxicity, quality of life, pharmacoeconomics, and genetic and biologic correlates that may help select more appropriate candidates for adjuvant therapies.     

Ovarian steroids modulate responsiveness to dopamine and expression of G-proteins in lactotropes

Considerable controversy surrounds the management of gastric cancer and this has largely overshadowed recent progress in our understanding of the epidemiology and molecular pathogenesis of the disease, and improvements in diagnostic and staging techniques. Differences identifiable in the molecular pathogenesis of the 'intestinal' and 'diffuse' types of gastric cancer may help to unravel the biological behaviour of variants and ultimately influence therapeutic strategies. Endoscopic ultrasound is well established as being accurate for T staging and the introduction of laparoscopy, with or without ultrasound, is obviating unnecessary laparotomy in non-bleeding, non-obstructed patients. Controversies in surgery encompass the role of laparoscopic surgery in early gastric cancer, the extent of lymphadenectomy including para-aortic nodal dissection, resection of en bloc contiguous organ involvement, pancreatosplenectomy, left upper abdominal evisceration, and modes of reconstruction (pylorus-preserving gastrectomy, pouch formation) to enhance quality of life. Whereas adjuvant chemotherapy does not impact favourably on survival, emphasis has now shifted to neoadjuvant (induction) chemotherapy to downstage the disease. Preoperative regional chemotherapy and intra-operative hyperthermic chemotherapy or irradiation may prove to be of benefit in patients with resectable disease, but some scepticism still exists as to the usefulness of biological response modifiers (e.g. OK432, PSK) for adjuvant treatment. Ethical issues relating to cultural differences in Asia sometimes mitigate against adequate trial design (e.g. a surgery-alone control group or a no adjuvant therapy treatment group may be considered inappropriate) and this has understandably hindered acceptance in Western countries of the value of current management practices in Asia. These issues and the need for ongoing well-conducted randomized trials with prospective subset analysis are now being addressed.     

Treatment of clinical stage I testicular cancer and a possible role for new biological prognostic parameters

Three different treatment strategies for patients with stage I non-seminomatous testicular cancer are available that will all result in long-term survival in more than 98% of the patients: a "wait and see" strategy with follow-up and chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy, with or without application of systemic chemotherapy, in cases of retroperitoneal metastases (pathological stage II disease) or primary adjuvant chemotherapy following inguinal orchiectomy. Each treatment strategy is associated with specific side-effects. In several studies histological characteristics of the primary tumour, particularly the presence of vascular invasion and of embryonal carcinoma cells, have been demonstrated to be significant prognostic factors for the risk of occult retroperitoneal metastases in patients with stage I disease. In addition, new biological prognostic factors determined by flow cytometry, cytogenetic analysis or molecular-biological DNA or RNA analysis have been investigated, among which alterations of the p53 tumour-suppressor gene may represent a promising new prognostic factor. Although alterations of p53 gene expression seem to be associated with advanced tumour stage and may predict retroperitoneal metastatic disease, the independent role of these molecular genetic alterations needs to be prospectively studied. Currently a risk-adapted treatment strategy based on the histological criteria of vascular invasion and the presence of embryonal carcinoma can be used to stratify patients into a "high-" and "low-risk" group with respect to tumour progression. While primary-nerve-sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles of platinum, etoposide and bleomycin may be appropriate for patients with a high risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used for "low-risk" (less than 15% risk of progression) patients. Molecular investigations of prognostic factors may be able to improve further the stratification of patients into these different risk categories.     

Adjuvant systemic chemotherapy in colon cancer

The prognosis for patients with cancer of the colon is dubious. An intendedly curative colon resection is performed in two-thirds of these patients, but half of them will subsequently die from metastatic disease. Randomized trials of adjuvant therapy with fluorouracil in combination with levamisole or leucovorin have shown significant benefit in terms of increased disease-free survival and overall survival. In 1990 adjuvant treatment was recommended as routine therapy in high risk patients in USA. A number of European countries are routinely treating high risk patients with Dukes' C coloncarcinoma. The recommendations are based on results from several cooperative trials reviewed in this article. Treatment related toxicity accelerates with increasing age but was acceptable in the reviewed trials. Adjuvant therapy is widely accepted as an important supplement to surgery in high risk patients. A Conference on the results and experiences now available should take place in the near future in order to establish a national consensus on adjuvant chemotherapy in Denmark. Patients with resected Dukes' C coloncarcinoma should receive adjuvant chemotherapy including 5-fluorouracil and leucovorin. Randomized trials are needed to establish the most effective regimens but "no-treatment" controls are no longer ethically acceptable.     

S-phase fraction and proportion of cells with high DNA content as prognostic factors of lymph node negative breast cancer

Breast cancer is the most frequent female cancer in Western Europe. Roughly half of the patients have no axillary lymph node involvement at time of operation. In this group of patients adjuvant treatment should only be undertaken in the subgroup with a high risk of recurrence. Suitable significant prognostic parameters are needed to identify patients at risk. S-phase fraction and the percentage of cells with a high DNA content are two prognostic factors that are determined by measuring total nuclear DNA and cell cycle analysis. Both were analyzed in large studies and have shown their impact on prognosis. However, divergent results underline the necessity for larger studies with a longer follow-up.