Prognostic criteria in patients with renal pelvic and ureteral cancers--clinical value of volume weighted mean nuclear volume

A retrospective, prognostic study was performed on 22 patients with transitional cell carcinoma of the upper urinary tract seen between Dec. 1982 and Jun. 1995. Unbiased estimates of volume weighted mean nuclear volume (MNV) were compared with age at the time of diagnosis, muscle invasion, and histological grading according to World Health Organization (WHO) classification on the prognostic value. Estimates of MNV were significantly correlated (p = 0.0135) only with disease-specific survival of transitional cell carcinoma of the upper urinary tract, contrary to age at the time of diagnosis (p = 0.4865), and muscle invasiveness (p = 0.1756). The analysis was not conclusive with regard to the WHO classification as the prognostic factor in this study. Estimates of MNV also were significantly correlated (p = 0.0325) with disease-specific survival in patients diagnosed histologically as grade 2. These findings indicate that estimates of MNV are useful for determining the prognosis of transitional cell carcinoma of the upper urinary tract.     

A double blind, prospective trial of topical ciprofloxacin versus normal saline solution in the treatment of otorrhoea

CONTEXT: The generalizability of currently available estimates of survival after radical prostatectomy is theoretically limited. OBJECTIVE: To obtain generalizable estimates of survival after radical prostatectomy. DESIGN: A population-based retrospective cohort study. SETTING: Nine regions of the United States. PATIENTS: Patients who were diagnosed with prostate cancer between 1983 and 1987 and underwent radical prostatectomy and lymph node dissection. MAIN OUTCOME MEASURES: Proportional hazards models incorporating geographical region, age, race, pathological stage, lymph node involvement, and tumor grade to identify independent correlates of disease-specific and overall survival and life table analyses to estimate 10-year survival distributions. RESULTS: A total of 3626 patients with a mean age of 65 years were included in the study; 92.6% were white, 54.2% had moderate-grade cancer, 60.4% had no extension beyond the prostate, and 91.2% had no lymph node involvement. Using San Francisco-Oakland, Calif, as a reference region, no other region was significantly associated with a risk of disease-specific or overall mortality. Older age and black race were independently associated with worse overall but not disease-specific survival. Higher grade, extension beyond the prostate, and lymph node involvement were independently associated with worse disease-specific and overall survival. Estimates of 10-year disease-specific survival ranged from 75% to 97% for patients with well-differentiated and moderately differentiated cancers and from 60% to 86% for patients with poorly differentiated cancers. CONCLUSIONS: Neither disease-specific nor overall survival varied by region, suggesting geographically uniform assessments of risk in patient selection for radical prostatectomy. Across regions, overall survival varied by patient and prostate cancer characteristics while disease-specific survival varied substantially by prostate cancer but not patient characteristics. The present analyses provide the most generalizable current estimates of survival after radical prostatectomy.     

Clinical studies on the prognostic factors in prostate cancer

To evaluate the prognostic factors and the outcome of treatment, a retrospective study was done on 141 patients with prostate cancer who were newly diagnosed at Kitano Hospital between January 1985 and November 1996. In recent years, the number of patients and the ratio of low stage cancer have increased. The overall 5-year crude survival rate was 49.9%. The 5-year crude survival rate for clinical stage A, B, C and D was 67%, 70%, 62% and 30% respectively. The overall 5-year disease-specific survival rate was 65.6%. The 5-year disease-specific survival rate for clinical stage A, B, C and D was 100%, 89%, 72% and 42%, respectively. By univariate analysis, clinical stage, Gleason score, prostate specific antigen (PSA) level, and patient age were prognostic factors for disease-specific survival of prostate cancer. According to Cox's regression analysis by the stepwise forward regression method, clinical stage and Gleason score were selected as more valuable prognostic factors than PSA level, patient age, comorbidity, and initial treatment. In Gleason score 2 to 8, the prognosis became significantly worse as clinical stage advanced, but in Gleason score 9 and 10 the prognosis was poor regardless of clinical stage.     

Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting

The biological potential of prostate cancer is highly variable and cannot be satisfactorily predicted by histopathological criteria alone. Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The aim of this study was to investigate whether microvessel density (MVD) at diagnosis was correlated with disease-specific survival in a non-curative treated population of prostate cancer patients. MVD was immunohistochemically (factor VIII-related antigen) quantified in archival tumours obtained at diagnosis in 221 prostate cancer patients. Median length of follow-up was 15 years. The maximal MVD was quantified inside a 0.25 mm2 area of the tumour and the median MVD was 43 (range 16-151) mm2. MVD was statistically significantly correlated with clinical stage (P < 0.0001) and histopathological grade (P < 0.0001). When dichotomized by the median counts, MVD was shown to be significantly associated (P = 0.0001) with disease-specific survival in the entire population as well as in the theoretically curable clinically localized subpopulation. A multivariate analysis demonstrated that MVD was a significant predictor of disease-specific survival in the entire cancer population (P = 0.0004), as well as in the clinically localized cancer population (P < 0.0001). These findings suggest that quantitation of angiogenesis reflects the spontaneous clinical outcome of prostate cancer.     

Usefulness of fine needle aspiration cytology in the diagnosis of prostate cancer

The efficacy of aspiration cytology, using Franzen method and echo-guided aspiration for prostate cancer was examined to 102 patients under saddle-block anesthesia in urological clinic of Chiba University Hospital. Between 1990 and 1993, 77 cases out of 102 patients were diagnosed histologically as prostate cancer by needle biopsy and 90% of them were coincidental with findings of aspiration cytology. Looking at histological grades, well differenciated cancer was shown to yield low positivity compared with moderately and poorly differentiated cancer. Positive rate showed similar when grade of specimens from needle biopsy was classified with Gleason pattern. Neither T category nor method of aspiration between Franzen and echo-guided methods influenced positive rate of aspiration cytology. On aspiration cytology, its grading revealed 60% of coincidence with that obtained by histological method. When counting more than 300 scattered cells, 90% of coincidence was achieved with histological grading. It is concluded that aspiration cytology is efficient for diagnosis of prostate cancer.     

Is prostate specific antigen density an important prognostic indicator for patients with prostate cancer treated with external beam therapy?

The purpose of this study was to determine if prostate specific antigen density (PSAD) is a predictor of outcome following external beam radiotherapy for prostate cancer, and to compare it with other prognostic factors. Between January 1990 and December 1993, 205 patients with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation, with no prior or adjuvant hormonal therapy. All patients had pre- and post-treatment serum prostate specific antigen (PSA) evaluation. They were followed up for at least 24 months. PSAD was defined as the ratio of pre-treatment serum PSA to the prostate volume, as determined from CT treatment planning scans. Prostate volumes were calculated using the prostate ellipse formula. Median PSA density was 0.37, with a range 0.01-6.7. Biochemical failure was defined as three consecutive rises in serum PSA, regardless of the magnitude of elevation. 4-year biochemical disease-free survival (BDFS) for patients with PSAD < or = 0.3 was 60%, compared with 22% for patients with PSAD > 0.3 (p = < 0.001). In a multivariate analysis, pre-treatment PSA (p = < 0.001), Gleason score (p = 0.002), and stage (p = 0.03) were independent predictors of BDFS, while PSAD was not an important prognosticator (p = 0.62). Pre-treatment serum PSA is the most important prognosticator of BDFS, following external beam radiotherapy, for patients with prostate cancer. PSA density did not predict treatment outcome.     

The dilemma of prostate cancer--a growing human and economic burden irrespective of treatment strategies

The prognostic value of the erythrocyte sedimentation rate (ESR) was investigated in a population-based prostate cancer study, comparing 556 patients treated with no intent to cure. The data originated from hospital charts and death certificates. A statistically significant relationship between ESR at diagnosis and overall as well as disease-specific survival was demonstrated by univariate and multivariate analyses. A similar result was demonstrated in the 179 patients suffering from clinically organ-confined (T1-2,Nx,M0) disease. In a subpopulation consisting entirely of clinically organ-confined, small (T1), well-differentiated tumors, the dichotomized ESR (< or =20 mm/h vs. >20 mm/h) at the time of diagnosis distinguished between aggressive and non-aggressive tumors. In a small, second prostate cancer population it was demonstrated that ESR was not a surrogate marker for prostate- specific antigen (PSA). Our results indicate that ESR is a significant predictor of survival in early localized prostate cancer.     

A randomized double-blind trial of ondansetron alone versus in combination with dexamethasone versus in combination with dexamethasone and lorazepam in the prevention of emesis due to cisplatin-based chemotherapy

Sixty-five cases of invasive breast cancer < or = 1 cm. in largest diameter (pT1a-b) were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA). The percentage of PC10 positive tumor cells was closely related to histological grading. No association was found between PC10 score and nodal status. ER-ICA was performed on 42 cases and showed no correlation with PC10 staining. The clinical behaviour of these tumors was excellent, with 5-year survival rates overall of 96% (90% disease free survival), and apparently unrelated to histological type and grade, nodal involvement and hormonal receptor status. The prognostic value of PCNA labeling rates remains nuclear in breast cancer of minimal size as well as in larger ones.     

Determination of angiogenesis adds information to estrogen receptor status in predicting the efficacy of adjuvant tamoxifen in node-positive breast cancer patients

There is experimental and clinical evidence that angiogenesis is involved in breast cancer progression and metastasis. To investigate whether the determination of angiogenesis adds prognostic information to the estrogen receptor (ER) status, we studied a series of 178 node-positive breast cancer patients, with a median follow-up time exceeding 5 years, treated with adjuvant tamoxifen (TAM). We assessed angiogenesis by the quantification of the intratumoral microvessel density and the determination of the Chalkley score using light microscopy. Microvessels were immunostained using the anti-CD31 antibody. The other features studied were ER status and the conventional clinicopathological prognostic indicators. Results were pooled from two collaborating Centers using Chalkley counts to convert intratumoral microvessel density to a common quantification system. We found that Chalkley score was not associated with any other feature studied. In univariate analysis, Chalkley score was significantly predictive of both relapse-free survival (RFS) and overall survival (OS; P < 0. 00001 and P = 0.00004, respectively). Likewise, ER status, the number of metastatic axillary nodes, histological grading, and tumor size were significantly predictive for RFS and OS. Cox multivariate analysis showed that Chalkley score was the strongest significant independent predictor of outcome. For RFS, ER status, the number of metastatic nodes, and histological grading also retained significance. For OS, the number of metastatic nodes, tumor size, and histological grading were independent prognostic factors. The joint assessment of the above variables had a satisfactory prognostic capability, as found using the Harrel statistics (c = 0. 77). These results suggest the validity of using Chalkley counts to assess and compare angiogenesis for prognostic purposes between different Centers. We found that angiogenesis adds significant prognostic information to ER status in predicting the outcome of breast cancer patients treated with adjuvant TAM. In fact, irrespective of the ER status, the patients with highly angiogenic tumors had a poor outcome, even if treated with TAM. For these patients, the inhibition of angiogenesis with specific angioinhibitory drugs may be a promising new therapeutic strategy.     

Focal neuroendocrine differentiation lacks prognostic significance in prostate core needle biopsies

PURPOSE: The biological behavior of prostate cancer is highly variable and cannot sufficiently be predicted by histological criteria alone. New prognostic factors are needed in core needle biopsies before initial treatment decisions. We investigate the prognostic significance of focal neuroendocrine differentiation in core needle biopsies of prostate cancer. MATERIALS AND METHODS: Core needle biopsies from 105 untreated patients (mean age 71 years) were immunohistochemically examined for focal neuroendocrine differentiation using an antibody against chromogranin A. Tumor cell proliferation was assessed with Ki-67 labeling index using MIB 1 antibody. The cause of death was determined by examination of records including autopsy reports. RESULTS: Focal neuroendocrine differentiation was found in 25% of the tumors. There was no association between the presence of focal neuroendocrine differentiation and Gleason score or Ki-67 labeling index. Tumor specific survival analysis revealed that high Gleason score and high Ki-67 labeling index were predictors of tumor specific death, whereas focal neuroendocrine differentiation failed to provide prognostic information. There was a significant increase in frequency and density of neuroendocrine differentiation between initial core needle biopsies and later specimens of secondary hormone resistant prostate cancer in 15 patients. CONCLUSIONS: In contrast to high Gleason score and high Ki-67 labeling index, focal neuroendocrine differentiation is not a prognostic factor in core needle biopsies of prostate cancer. Focal neuroendocrine differentiation seems to appear more frequently and intensively in hormone resistant prostate cancer, supporting a role of neuroendocrine cells in the development of hormone refractory disease.     

Calcium channel blocker use and the risk of prostate cancer

A recent study suggested that the risk of all cancers, including prostate cancer, is increased by the use of calcium channel blockers. The objective of this study was to determine whether prostate cancer is associated with calcium channel blocker use. A case-control study was conducted in Massachusetts using cases diagnosed from December 1992 through February 1995. Cases were men identified by tumor registrars who were less than 70 years old with newly diagnosed prostate cancer. Controls were men with no history of prostate cancer or symptoms of undiagnosed prostate cancer, and were matched to the cases on precinct of residence and half-decade of age. A total of 1217 cases of prostate cancer and 1400 community controls are included in this analysis. Data were collected by telephone interview. Multiple logistic regression was used to estimate relative risks for calcium channel blockers use while controlling for confounding. The relative risk for prostate cancer for any use of calcium channel blockers relative to nonuse was 1.2 (95% confidence interval [CI], 0.9-1.5). There was no evidence of a trend according to duration of use. When the analysis was confined to symptomatic men, the relative risk estimate was 1.1 (0.8-1.4) overall and 1.2 (0.8-1.7) among those aged 65 to 69 years. Relative risk estimates for the use of other classes of antihypertensive drugs among symptomatic men were close to 1.0; the corresponding estimates among asymptomatic men were generally further from 1.0. These findings suggest that calcium channel blockers do not increase the risk of prostate cancer. The differences in the relative risk estimates between symptomatic and asymptomatic men are compatible with detection bias. Because of the widespread use of Prostate-Specific Antigen testing for early detection of prostate cancer, potential detection bias needs to be considered in future studies of prostate cancer.     

Effect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro

The clinical relevance of grading in ependymomas is almost always regarded as controversial. According to the classification of brain tumours revised by the World Health Organization (WHO) in 1993, brain tumours of ependymal origin are differentiated as subependymomas Grade I, ependymomas Grade II, and anaplastic (malignant) ependymomas Grade III. The purpose of the present retrospective study of 126 patients with intracranial ependymomas was to assess the clinical and prognostic significance of the topical classification and grading system by a uni- and multivariate statistical analysis. 87 Grade II ependymomas were predominantly located in the midline and in the fourth ventricle, whereas 39 anaplastic ependymomas Grade III were most often found in the cerebral hemispheres. Excluding the localization-linked operative mortality, progression-free survival (PFS) was significantly dependent on the histological grading. Median PFS time was 7.5 years in Grade II, but only 1.5 years in Grade III ependymomas. Stratifying for the two time intervals 1951-1970 and 1971-1990, and excluding the operative mortality, a multivariate Cox' model analysis of the covariates age, localization, grading, extent of surgery, and radiation therapy revealed that only the histological grading and radiation therapy had a significant impact on PFS. Thus, the WHO grading system has a statistically significant relevance for the long-term prognosis of intracranial ependymomas. However, the therapeutic management including radical tumour resection and additional local irradiation should be independent of the grading.     

Na+/H+ exchanger (NHE) in the basolateral membrane is encoded by NHE-1 mRNA in LLC-PK1 clone 4 cells

Clinical follow-up data of 276 colorectal adenocarcinoma patients treated in Kuopio University Hospital between 1976 and 1986 and followed up for a mean of 14 years were analysed. The clinical findings were correlated with tumour-infiltrating lymphocytes (TILs) and with histological and quantitative factors including nuclear parameters and volume-corrected mitotic index. In univariate survival analysis, TNM classification, Dukes' stage, histological grade, and TILs were significant predictors of survival. TNM classification, Dukes' stage, and TILs also predicted recurrence-free survival. In multivariate analysis, TILs were an independent prognostic factor of survival in all cases, as well as in patients with T1-4N0-3M0 and T1-4N1-3M1. TILs also independently predicted recurrence-free survival. TILs can provide important prognostic information in colorectal cancer to be used in evaluating for adjuvant therapy in different tumour stages.     

Screening for prostate cancer

In an attempt to detect prostate cancer when the tumor is still confined to the prostate, a screening program was established. We studied the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) in the early detection of prostate cancer. One thousand men aged 50-75 years underwent DRE and serum PSA determination. Transrectal ultrasound-guided biopsies were obtained in each case of a suspicious DRE. Six systematic biopsies were performed if the PSA level was > 10 ng/ml, even if DRE and transrectal ultrasonography revealed no areas suspicious of cancer. A suspicious DRE was noted in 11.5% of the subjects; 16% had elevated levels of serum PSA (> 4 ng/ml) and 3.9% had serum PSA > 10 ng/ml. Biopsies were obtained from 90 patients, of which 31 were positive for prostate cancer. The cancer detection rate was 2.2% for DRE, 2.0% for PSA > 10 ng/ml, and 3.1% for the two methods combined. Clinical staging revealed that in 29 of the 31 patients with prostate cancer, the tumor was confined to the prostate: Stage A in 9 cases and stage B in 20 cases. Only two patients had clinically advanced cancer, and 22 patients underwent radical prostatectomy. Pathological examination disclosed biologically significant tumors in 91% of the cases in terms of tumor volume and grade. Although there is little evidence that screening will result in the reduction of the disease-specific mortality rate, early detection of prostate cancer by DRE, serum PSA, and transrectal ultrasound should be encouraged.     

Large sample Bayesian inference on the parameters of the proportional hazard models

This paper considers large sample Bayesian analysis of the proportional hazards model when interest is in inference on the parameters and estimation of the log relative risk for specified covariate vectors rather than on prediction of the survival function. We use a normal prior distribution for the parameters and make inferences based on the derived posterior distribution. The suggested approach is much simpler than alternative Bayesian analyses previously suggested for the proportional hazards models. Using simulated data we compare estimates obtained from the Bayesian analysis with those obtained from the full proportional hazards model and the reduced model after backwards elimination. We show that under a wider range of assumptions, the Bayesian analysis provides reduced estimation errors and improved rejection of noise variables. Finally, we illustrate the methodology using data from a large study of prognostic markers in breast cancer.     

DNA ploidy, proliferative index and EGF-R status in 130 cases of resected gastric cancer--a multivariate analysis

BACKGROUND/AIMS: The purpose of this study was to define the prognostic role of DNA ploidy, proliferative index and EGF-R status in resected gastric cancer. MATERIALS AND METHODS: Ten clinico-pathological parameters and three biological factors obtained from flow cytometry and immunohisto-chemistry were evaluated in a series of 130 gastric cancer patients who received surgical treatment, including 28 stage IV cases (21.6%), using paraffin-embedded and fresh specimens in 77.7% and 22.3% of the cases, respectively. These variables were first analyzed and tested for correlation within the whole series and then weighted against survival in 117 applicable cases through univariate and multivariate analyses. RESULTS: Aneuploidy was significantly related to higher proliferative activity, EGF-R expression and deeper stomach wall infiltration. Higher proliferative activity was significantly related to deeper stomach wall infiltration and larger tumor diameter. The latter showed a significant relationship to EGF-R expression. Univariate analysis showed the significant variables for survival to be DNA ploidy, pT, pN, M, stage, histological type according to Lauren and tumor diameter. Multivariate analysis calculated on these significant variables using the Cox multiple stepwise regression model detected three factors which independently influence survival: pathological stage (p < 0.00001), histological type according to Lauren (p < 0.002) and DNA ploidy (p < 0.03). CONCLUSIONS: DNA ploidy was shown to be a significant prognostic parameter in resected gastric cancer after pathological stage and histological type according to Lauren. The prognostic roles of proliferative activity and EGF-R status require further investigation.     

Parietal motor syndrome: a clinical description in 32 patients in the acute phase of pure parietal strokes studied prospectively

Although survival rates are useful for monitoring progress in the early detection and treatment of cancer and are of particular interest to patients with new diagnoses, there are limited population-based estimates of long-term survival rates. We used data collected by the Surveillance, Epidemiology, and End Results Program for cases diagnosed during 1974-1991 and followed through 1992 to estimate relative survival at 5, 10, and 15 years after diagnosis of cancer of the breast, prostate, colon and rectum, and lung. Relative survival after diagnosis of breast and prostate cancer continued to decline up through 15 years after diagnosis, whereas survival after diagnosis of lung and colon or rectal cancer remained approximately constant after 5 and 10 years, respectively. Age-specific patterns of survival varied by site, stage, and demographics. Among patients with localized breast and prostate cancer, women who were younger than age 45 at breast cancer diagnosis and men who were 75 years and older at prostate cancer diagnosis had the poorest relative survival. Relative survival among lung cancer patients decreased with age at diagnosis, regardless of stage or demographics, and age-specific patterns of relative survival for patients with cancer of the colon and rectum differed according to race. Among white patients diagnosed with cancers of the colon and rectum, relative survival did not vary by age at diagnosis; among black patients older than 45 at diagnosis, relative survival decreased with age. This study provides population-based estimates of long-term survival and confirms black/white, male/female, and stage- and age-specific differences for the major cancers.     

Results of radical prostatectomy in men with clinically localized prostate cancer

OBJECTIVE: To assess the results of radical prostatectomy in men with early prostate cancer. DESIGN: Retrospective, nonrandomized, multi-institutional pooled analysis. SETTING: Eight university medical centers in the United States and Europe. PATIENTS: A total of 2758 men with stage Tl and T2 prostatic cancer. MAIN OUTCOME MEASURES: Disease-specific and metastasis-free survival rates. RESULTS: Tumor grade was the most important preoperative factor in determining outcome. Disease-specific survival 10 years following surgery and associated 95% confidence intervals were 94% (range, 87%-98%), 80% (range, 74%-85%), and 77% (range, 65%-86%) for those men with grade 1, 2, and 3 tumors, respectively. Metastasis-free survival at 10 years was 87% (range, 78%-92%), 68% (range, 62%-73%), and 52% (range, 38%-64%) for patients with grade 1, 2, and 3 cancers, respectively. CONCLUSIONS: Radical prostatectomy leads to high 10-year disease-specific survival rates in men with all tumor grades. However, caution is needed in comparing these results with similar studies of alternative treatment strategies, such as watchful waiting, due to the inherent potential biases in uncontrolled trials. Nevertheless, these results offer the best currently available estimates of 10-year outcome of radical prostatectomy in men with clinically localized prostate cancer and may be useful in counseling patients with early malignancy.     

High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival

We recently reported that alpha 6 integrin mediates experimental metastasis in mice by functioning in the adhesion of tumor cells to the vascular endothelium. In the current study, we investigated the expression of human alpha 6 integrin in invasive breast carcinomas of 119 women. In 50% of the tumors alpha 6 integrin was expressed in the majority of the cells, and this expression was correlated with reduced survival time. By contrast, the 24% of patients with breast tumors devoid of alpha 6 integrin expression all survived. The tumors were also evaluated for clinical risk factors including histological grading and steroid receptor level. The combination of these factors with alpha 6 integrin expression was superior in predicting overall survival than considering the other factors alone. The correlation with decreased survival time was consistent, regardless of whether the tumors expressed the alpha 6 integrin A or B forms, which differ in their cytoplasmic domain. On the basis of this pilot study we consider alpha 6 integrin expression to be a novel prognostic marker for human breast cancer.     

Role and limits of glycemic regulation in the pathogenesis of diabetic microangiopathy

A retrospective study of 167 consecutive radically treated breast cancer patients with histopathologically confirmed ductal carcinoma is presented. The aim was to establish the prognostic significance and reproducibility of histopathological grading done independently by two pathologists. Further-more, the value of measurements of mean nuclear area (MNA) in the primary tumour was assessed. The two pathologists reviewed the same histological sections using a three-point scoring system based on tubular structures, number of mitoses and nuclear pleomorphism. Grading was identical for 70% of the tumours (Kappa value 0.51). With increasing MNA, the fraction of poorly differentiated tumours increased. In the univariate analysis, tumour-related survival was significantly related to histopathological grading when G3 tumours were compared to G1/G2 tumours (p < 0.05). In the multivariate analysis, tumour size (pT category), lymph-node status and grading were the only significant factors influencing patient outcome (p < 0.05). MNA had no significant prognostic value. A combination of tumour size and histopathological grading identifies a group of node-negative patients (pT2 G2/G3) who may have a less favourable prognosis and for whom adjuvant treatment may be beneficial.