The association between tumour sub-site and local nodal and/or distant metastasis at the time of resection of colorectal cancer: a prospective study of 3,360 consecutive cases.

The concept that right and left sided colorectal cancer may be biologically different has led to a review of the pathology and molecular characteristics expressed by the two sides. The aim of this cross-sectional study was to examine the association between tumour sub-sites and the presence of any metastasis by multivariable modelling. Pathology data were drawn from a hospital series of 3360 consecutive patients who had their first cancer resected between 1995 and 2019 inclusive. A preliminary analysis of the distribution of sex, age and a range of routinely reported pathology features showed that the simple division of the bowel into right and left sides masks the considerable variation in pathology features which occurs between sub-sites within each side. Logistic regression adjusting for sex, age, a range of routinely reported pathology features and tumour sub-site showed that age ≤70, direct tumour spread (T3 and T4), high grade, venous invasion and perineural invasion all carried a significantly increased risk for the presence of metastatic spread. The only tumour sub-sites to show an increased risk were the sigmoid colon and rectum (adjusted odds ratio 1.72, P < 0.001 and 1.78, P < 0.001, respectively). These findings suggest that multivariable modelling could usefully be applied to identify associations between sub-sites and molecular characteristics.

Apical Node Involvement Does Not Influence Prognosis After Potentially Curative Resection for Stage III Colorectal Cancer: A Competing Risks Analysis.

OBJECTIVE: To examine the independent prognostic value of ALN status in patients with stage III CRC. SUMMARY OF BACKGROUND DATA: Early CRC staging classified nodal involvement by level of involved nodes in the operative specimen, including both locoregional and apical node status, in contrast to the American Joint Committee on Cancer/tumor nodes metastasis (TNM) system where tumors are classified by the number of nodes involved. Whether ALN status has independent prognostic value remains controversial. METHODS: Consecutive patients who underwent curative resection for Stage III CRC from 1995 to 2012 at Concord Hospital, Sydney, Australia were studied. ALN status was classified as: (i) ALN absent, (ii) ALN present but not histologically involved, (iii) ALN present and involved. Outcomes were the competing risks incidence of CRC recurrence and CRC-specific death. Associations between these outcomes and ALN status were compared with TNM N status results. RESULTS: In 706 patients, 69 (9.8%) had an involved ALN, 398 (56.4%) had an uninvolved ALN and 239 (33.9%) had no ALN identified. ALN status was not associated with tumor recurrence [adjusted hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.84-1.26] or CRC-specific death (HR 1.14, CI 0.91-1.43). However, associations persisted between TNM N-status and both recurrence (HR 1.58, CI 1.21-2.06) and CRC-specific death (HR 1.59, CI 1.19-2.12). CONCLUSIONS: No further prognostic information was conferred by ALN status in patients with stage III CRC beyond that provided by TNM N status. ALN status is not considered to be a useful additional component in routine TNM staging of CRC.

Recurrence and colon cancer-specific death in patients with large bowel obstruction requiring urgent operation: a competing risks analysis.

AIM: Clinical presentation with large bowel obstruction has been proposed as a predictor of poor long-term oncological outcomes after resection for colorectal cancer. This study examines the association between obstruction and recurrence and cancer-specific death after resection for colon cancer. METHOD: Consecutive patients who underwent resection for colon cancer between 1995 and 2014 were drawn from a prospectively recorded hospital database with all surviving patients followed for at least 5 years. The outcomes of tumour recurrence and colon cancer-specific death were assessed by competing risks multivariable techniques with adjustment for potential clinical and pathological confounding variables. RESULTS: Recurrence occurred in 271 of 1485 patients who had a potentially curative resection. In bivariate analysis, obstruction was significantly associated with recurrence [hazard ratio (HR) 2.23, CI 1.52-3.26, p < 0.001] but this association became nonsignificant after adjustment for confounders (HR 1.53, CI 0.95-2.46, p = 0.080). Colon cancer-specific death occurred in 238 of 295 patients who had a noncurative resection. Obstruction was not significantly associated with cancer-specific death (HR 1.02, CI 0.72-1.45, p = 0.903). In patients who had a noncurative resection, the competing risks incidence of colon cancer-specific death was not significantly greater in obstructed than in unobstructed patients (HR 1.02, CI 0.72-1.45, p = 0.903). CONCLUSION: Whilst the immediate clinical challenge of an individual patient presenting with large bowel obstruction must be addressed by the surgeon, the patient's long-term oncological outcomes are unrelated to obstruction per se.

Competing risks analysis of the effect of local residual tumour on recurrence and cancer-specific death after resection of colorectal cancer: implications for staging.

The pTNM staging system for colorectal cancer (CRC) is not entirely effective in discriminating between potentially curative and non-curative resections because it does not account for local residual tumour in patients with stages I, II or III. This study aimed to evaluate the prognostic importance of histologically verified tumour in any line of resection of the bowel resection specimen (TLR) in relation to pTNM stages and to demonstrate how TLR may be integrated into pTNM staging. Information on patients in the period 1995 to 2010 with complete follow-up to the end of 2015 was extracted from a prospective database of CRC resections. The outcome variables were the competing risks incidence of CRC recurrence and CRC-specific death. After exclusions, 2220 patients remained. In 1930 patients with pTNM stages I-III tumour, recurrence was markedly higher in those with TLR than in those without (HR 6.0, 95% CI 4.2-8.5, p < 0.001) and this persisted after adjustment for covariates associated with recurrence. CRC-specific death was markedly higher in the presence of TLR (HR 7.7, CI 5.3-11.2, p < 0.001), which persisted after adjustment for relevant covariates. These results justify removing patients with TLR from pTNM stages I to III and placing them in stage IV, thereby allowing the categorisation of all patients with any known residual tumour into three prognostically distinct groups. This study demonstrates how TLR may be integrated into pTNM staging, thus improving the definition of the three stages which are considered potentially curable (I, II and III).

Pathological outcomes in rectal cancer following laparoscopic surgery.

AIM: This study examined pathological quality-of-surgery indicators in laparoscopic and open rectal cancer resection specimens. METHODS: Retrospective analysis of consecutive, prospectively recorded laparoscopic (LR) or open (OR) resections for rectal cancer. Indicators included integrity of the perirectal fascial envelope, circumferential margin clearance, lymph node yield and distal margin clearance. RESULTS: Between January 2007 and December 2013, 168 LR and 189 OR were performed. Univariate analysis showed that the presence of tumor within 1 mm of the circumferential margin was lower in LR (13/168 vs 28/189 cases, P = 0.039) as was a distal margin of clearance of < 1 cm (3/165 vs 12/186, P = 0.032). There was no difference in the surgical disruption of the fascial envelope (P = 0.091) or the percentage of specimens with a lymph node yield < 12 (P = 0.576) between the LR and OR groups. Multivariate analysis did not reveal any significant differences in pathological outcomes. CONCLUSION: With careful case selection, laparoscopic surgery has similar pathological outcomes to open surgery for rectal cancer.

Trends in pathology and long-term outcomes after resection of colorectal cancer: 1971-2013.

BACKGROUND: The aim of this study was to describe temporal trends in tumour pathology and long-term outcomes in 5217 patients recorded in a registry of colorectal cancer resections initiated at Concord Hospital, Sydney, Australia, in 1971. METHODS: This report is based on consecutive resections up to December 2013, with no exclusions. Categories in variables examined were expressed as percentages over annual totals of relevant patients or annual mean values. The statistical significance of temporal trends was examined by least squares regression. RESULTS: The percentages of patients with local spread beyond the muscularis propria, nodal metastasis, distant metastasis and tumour in a line of resection all declined significantly. In consequence, the percentage of stage D patients fell, whereas the percentage in stage A rose. Other tumour variables that increased significantly were polypoid morphology, contiguous adenoma and invasion of a free serosal surface. Tumours in which an adherent adjacent structure was partly or completely removed also increased. There were significant declines in high-grade malignancy, venous invasion and tumour size. The recurrence rate for rectal cancers declined significantly, whereas for rectal and colonic cancers combined, both the overall 5-year survival rate and the 5-year cancer-specific survival rate increased markedly. CONCLUSION: These results show a reduction in adverse pathology findings and favourable trends in recurrence and survival after colorectal cancer resections in a high-incidence country over a period of 43 years.

Trends in short-term outcomes after resection of colorectal cancer: 1971-2013.

BACKGROUND: The aim of this study was to describe temporal trends in presentation, surgical management and immediate postoperative outcomes in patients recorded in a registry of colorectal cancer resections that was initiated at Concord Hospital, Sydney, Australia, in 1971. A companion paper describes tumour pathology and long-term recurrence and survival. METHODS: This report is based on 5217 consecutive resections up to 2013, with no exclusions. Categories in variables examined were expressed as percentages over annual totals of relevant patients or annual mean values. The statistical significance of trends was examined by least squares regression. RESULTS: The percentage of asymptomatic patients increased over time, whereas urgent presentations declined. Tumour size declined. The percentage of rectal cancers fell but the percentage of low rectal tumours rose. Initially, restorative rectal resections increased rapidly but later remained stable. There was no trend in medical complications, whereas surgical complications declined. Anastomotic leakage after restorative rectal resections declined but it was low and stable for colonic tumours. The rate of early reoperation remained stable, whereas 30-day mortality declined. Neoadjuvant radiotherapy for rectal cancer and adjuvant chemotherapy for stages B and C were introduced in 1992 and applied increasingly thereafter. CONCLUSION: Our findings, based on a 43-year prospective study, indicate sustained trends towards the earlier diagnosis of colorectal cancer and favourable short-term outcomes following bowel resection.

Reporting in studies of protein biomarkers of prognosis in colorectal cancer in relation to the REMARK guidelines.

PURPOSE: The REMARK guidelines give authors comprehensive and specific advice on the complete and transparent reporting of studies of prognostic tumor markers. The aim of this study was to use the REMARK guidelines to evaluate the quality of reporting in a sample of studies assessing tissue-based protein markers for survival after resection of colorectal cancer. EXPERIMENTAL DESIGN: Eighty pertinent articles were scored according to their conformity to 26 items derived from the REMARK criteria. RESULTS: Overall, on a scale of adequacy of reporting that potentially ranged from 26 to 78, the median for these studies was 60 (interquartile range 54-64) and several criteria were adequately covered in a large proportion of studies. However, others were either not dealt with or inadequately covered, including description of the study design (35%), definition of survival endpoints (48%), adjuvant therapy (54%), follow-up procedures and time (59%), neoadjuvant therapy (63%), inclusion/exclusion criteria (73%), multivariable modeling methods and results (74%), and discussion of study limitations (85%). CONCLUSIONS AND CLINICAL RELEVANCE: Inadequacies in presentation militate against comparability among protein marker studies and undermine the generalizability of their findings. The quality of reporting could be improved if journal editors were to require authors to ensure that their work satisfied the REMARK criteria.

Epithelial and stromal cell urokinase plasminogen activator receptor expression differentially correlates with survival in rectal cancer stages B and C patients.

Urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for colorectal cancer (CRC) patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE) or stroma-associated cells (uPARS)) and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs) could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC) patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively) reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007), reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC.

Complications after resection of colorectal cancer in a public hospital and a private hospital.

BACKGROUND: To our knowledge, immediate post-operative complication rates after resection of colorectal cancer (CRC) have not been compared between public and private hospitals in the Australian health care system. We compared the frequency of surgical and medical complications between a public tertiary referral hospital and a private hospital. METHODS: Data were drawn from a prospective registry of all patients having a resection for CRC between 2000 and 2010 performed by members of the Concord Hospital colorectal surgical unit, either at this hospital or at a single private hospital with which they were affiliated. Complication rates were compared after adjustment for preoperative and perioperative features by logistic regression. RESULTS: Among the 16 surgical complications, the only significant difference after adjustment for other features was a higher rate of septicaemia in the public hospital (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.6). Among the seven medical complications, the only significant differences were a higher risk of cardiac complications in patients with cardiac co-morbidity (OR 1.8, 95% CI 1.1-3.0) and of respiratory complications in patients without respiratory co-morbidity (OR 3.1, 95% CI 2.2-5.9) in the public hospital. CONCLUSION: In this study, where the same group of surgeons performed all reported CRC resections in the two hospitals, no independent effect of the type of hospital was found on 15 of 16 surgical complications and 5 of 7 medical complications. Type of hospital had no impact on rates of specific complications apart from septicaemia and cardiorespiratory complications, which were higher in the public hospital.

Mural and extramural venous invasion and prognosis in colorectal cancer.

BACKGROUND: Extramural venous invasion is a known independent predictor of poor prognosis after resection of colorectal adenocarcinoma, but the prognostic value of mural venous invasion alone and the association between venous invasion and prognosis within tumor stages has received little research attention. OBJECTIVE: This study aimed to determine whether associations between mural and extramural venous invasion and outcome differ among tumor stages after adjustment for other factors known to influence prognosis. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: Data were drawn from a registry of 3040 consecutive patients undergoing resection between 1980 and 2005 under the care of specialist surgeons in a tertiary referral public hospital and an affiliated private hospital. A standardized protocol was used for the pathological assessment of specimens. MAIN OUTCOME MEASURES: The primary outcomes measured were overall survival, cancer-specific survival, and recurrence. RESULTS: There was no significant association between venous invasion and survival in stages A (n = 544) or B (n = 1078). In stage C (n = 899), overall survival time was significantly shorter in patients with mural invasion alone or extramural invasion (both p < 0.001) than in those without invasion, and this persisted after adjustment for other prognostic variables. Equivalent bivariate associations were found in stage D, but only the effect of extramural invasion persisted after adjustment. LIMITATIONS: Our findings arise from the experience of a single surgical group and may not be generalizable to other settings. Only hematoxylin and eosin staining was used. CONCLUSIONS: The association between venous invasion and prognosis was stage specific. Both mural venous invasion alone and extramural venous invasion independently predicted overall survival in patients with stage C tumors, but not in patients with stages A, B, or D tumors. Although mural invasion alone was rare, the separate reporting of both mural and extramural invasion in patients with stage C tumor is informative and desirable.

Correlations between integrin ανß6 expression and clinico-pathological features in stage B and stage C rectal cancer.

Integrin ανß6 is highly expressed in a range of human cancers and frequently correlates with patient survival. This study examines correlations between ανß6 expression and patient clinico-pathological features in Stage B and Stage C rectal cancer, including overall survival. Expression of ανß6 was measured in 362 Stage B or C rectal cancer tissue samples at the tumour central region, invasive tumour front and adjacent non-neoplastic mucosa using immunohistochemistry. Distribution of ανß6 was found to be significantly higher at the invasive front compared to central regions of the tumour (p<0.001) or adjacent non-neoplastic mucosa (p<0.001) suggesting ανß6 plays a role in tumour cell invasion. However, integrin ανß6 expression was not associated with clinico-pathological features or overall survival indicating it is not an independent prognostic marker differentiating Stage B or C rectal cancer. Previous ανß6 studies have suggested the expression of ανß6 is involved in the earlier stages (i.e. Stages A/B) of tumour progression rather than the later stages (i.e. Stages C/D). However, our study has revealed that in rectal cancer ανß6 expression does not increase between Stages B and C, but may occur earlier, namely before or during Stage B cancer.

The cost of teaching an intern in New South Wales.

OBJECTIVE: To determine the cost of formal and informal teaching specifically provided for interns and to determine how much of an intern's time is spent in these activities. DESIGN, SETTING AND PARTICIPANTS: Costs of formal teaching for 2012 were obtained from the New South Wales Health Education and Training Institute (HETI) and costs of informal teaching by a survey of all interns in a random sample of prevocational networks. MAIN OUTCOME MEASURES: The cost of formal intern education provided by HETI; the number of hours of formal teaching provided to interns in hospital; intern estimates of the amount of non-timetabled teaching received in a typical week. RESULTS: The cost of formal teaching was $11 892 per intern per year and the cost of informal teaching was $2965 per intern per year (survey response rate, 63%) - a total of $14 857. Interns spent 2 hours per week in formal teaching and 28 minutes per week in informal teaching, representing 6.2% of a 40-hour week. CONCLUSION: The time of professionals paid by NSW Health represents most of the expenditure on teaching interns. An increase in time spent on intern teaching beyond the current 6.2% of an intern's 40-hour week would be an investment in better health care.

KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer.

Colonic and rectal cancers differ in their clinicopathologic features and treatment strategies. Molecular markers such as gene methylation, microsatellite instability and KRAS mutations, are becoming increasingly important in guiding treatment decisions in colorectal cancer. However, their association with clinicopathologic variables and utility in the management of rectal cancer is still poorly understood. We analyzed CDKN2A gene methylation, CpG island methylator phenotype (CIMP), microsatellite instability and KRAS/BRAF mutations in a cohort of 381 rectal cancers with extensive clinical follow-up data. BRAF mutations (2%), CIMP-high (4%) and microsatellite instability-high (2%) were rare, whereas KRAS mutations (39%), CDKN2A methylation (20%) and CIMP-low (25%) were more common. Only CDKN2A methylation and KRAS mutations showed an association with poor overall survival but these did not remain significant when analyzed with other clinicopathologic factors. In contrast, this prognostic effect was strengthened by the joint presence of CDKN2A methylation and KRAS mutations, which independently predicted recurrence of cancer and was associated with poor overall and cancer-specific survival. This study has identified a subgroup of more aggressive rectal cancers that may arise through the KRAS-p16 pathway. It has been previously shown that an interaction of p16 deficiency and oncogenic KRAS promotes carcinogenesis in the mouse and is characterized by loss of oncogene-induced senescence. These findings may provide avenues for the discovery of new treatments in rectal cancer.

Preoperative neutrophil/lymphocyte ratio predicts overall survival but does not predict recurrence or cancer-specific survival after curative resection of node-positive colorectal cancer.

BACKGROUND: The preoperative ratio of neutrophils to lymphocytes (NLR) has been proposed as a marker of poor outcome in patients having a resection for colorectal cancer (CRC). This study investigated the association between NLR and overall survival, cancer-specific survival and recurrent cancer in patients who had a potentially curative resection for node-positive CRC. METHODS: Data on 322 patients were drawn from a prospectively recorded registry operated on between 1999 and 2007. Analyses of survival involved the Kaplan-Meier method, Cox regression and competing risks Cox regression. RESULTS: Increasing NLR as a continuous variable was independently though weakly associated with diminishing overall survival after adjustment for other prognostic variables (HR 1.06, 95% CI 1.01-1.11, p = 0.013). Receiver operating characteristic analysis to dichotomize NLR as a predictor of overall survival yielded relatively poor sensitivity (55%), specificity (66%) and positive predictive value (56%, CI 47%-64%). Competing risks regression also showed that NLR was not independently associated with recurrence at any site (HR 1.04, CI 0.97-1.11, p = 0.241) or CRC-specific mortality (HR 1.02, CI 0.92-1.12, p = 0.782) but was associated with non-CRC mortality (HR 1.09, CI 1.03-1.15, p = 0.004). CONCLUSION: In patients with stage C tumor the weak link between NLR and overall mortality was not specific to CRC but apparently arose because patients with an elevated inflammatory status preoperatively were likely to progress to earlier death but not necessarily because of their cancer.

Cause-specific mortality and 30-year relative survival of Crohn's disease and ulcerative colitis.

BACKGROUND: Data from the northern hemisphere suggest that patients with ulcerative colitis (UC) have similar survival to the general population, whereas mortality in Crohn's disease (CD) is increased by up to 50%. There is a paucity of data from the southern hemisphere, especially in Australia. METHODS: A prevalence cohort (1977-1992) of patients with inflammatory bowel disease (IBD) diagnosed after 1970 was studied. Survival status data and causes of death up to December 2010 were extracted from the National Death Index. Relative survival analysis was carried out separately for men and women. RESULTS: Of 816 cases (384 men, 432 women; 373 CD, 401 UC, 42 indeterminate colitis), 211 (25.9%) had died by December 2010. Median follow-up was 22.2 years. Relative survival of all patients with IBD was not significantly different from the general population at 10, 20, and 30 years of follow-up. Separate analyses of survival in CD and UC also showed no differences from the general population. There was no difference in survival between patients diagnosed earlier (1971-1979) or later (1980-1992). At least 17% of the deaths were caused by IBD. Fatal cholangiocarcinomas were more common in IBD (P < 0.001), and fatal colorectal cancers more common in UC (P = 0.047). CONCLUSIONS: In Australia, IBD patient survival is similar to the general population. In contrast to data from Europe and North America, survival in CD is not diminished in Australia. IBD caused direct mortality in 17%, especially as biliary and colorectal cancers are significant causes of death.

Risk factors for prolonged ileus after resection of colorectal cancer: an observational study of 2400 consecutive patients.

OBJECTIVE: Prolonged ileus-the failure of postoperative ileus to resolve within a few days after major abdominal surgery-leads to significant medical consequences for the patient and costs to the hospital system. The aim of this retrospective analysis of prospectively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer. METHODS: Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995-2009. Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression. RESULTS: Prolonged ileus occurred in 14.0% of patients. Statistically significant independent predictors of prolonged ileus were male sex (OR: 1.7, P < 0.001), peripheral vascular disease (OR: 1.8, P < 0.001), respiratory comorbidity (OR: 1.6, P < 0.001), resection at urgent operation (OR: 2.2, P < 0.001), perioperative transfusion (OR: 1.6, P < 0.010), stoma constructed (OR: 1.4, P < 0.001), and operation lasting ≥3 hours (OR: 1.6, P < 0.001). CONCLUSIONS: These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them. These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment.

Use of adjuvant chemotherapy in stage C (III) rectal cancer: comparison of data from matched patients in a teaching hospital's clinico-pathological database.

AIMS: Controversy continues regarding the treatment of patients with resectable rectal cancer, particularly in regard to the effects of adjuvant therapies on long-term survival. The benefits of adjuvant chemotherapy alone in patients with stage III rectal cancer after curative resection remain unclear. The aim of this study was to compare the overall survival of patients who had received adjuvant chemotherapy after resection of a stage III rectal cancer (111 patients) with the survival of a historical control group who had surgery alone before chemotherapy was introduced (129 patients). METHODS: Treatment and outcomes data were drawn from a prospective hospital registry of consecutive patients who had a resection for stage III rectal cancer. RESULTS: The estimated Kaplan-Meier overall 5-year survival rate in patients who received chemotherapy (68.7%, 95% CI 58.3-77.1%, log-rank P < 0.001) was improved compared with the historical controls (40.5%, 95% CI 31.4-49.5%, log-rank P < 0.001). No systematic differences between the treated and control group were found. CONCLUSION: This study has shown improved survival after adjuvant chemotherapy in patients with stage III rectal cancer as compared with historical controls treated by surgery alone. Hence, there could be subsets of patients whom when treated with surgery in a specialized surgical unit, may benefit from chemotherapy and spared the toxicities of adjuvant radiotherapy. This should be explored further in a cooperative trial group setting.