Cause-specific Survival In Patients Research Articles

Prognostic significance of p53 and matrix metalloproteinase‐9 expression in follicular lymphoma

p53 mutations and high protein expression are associated with adverse prognosis in several lymphoma subtypes. Matrix metalloproteinase-9 (MMP-9) has also been found to correlate with poor survival in all lymphomas studied. The data concerning the clinical role of protein expression of p53 or gelatinases and their inhibitors in follicular lymphoma are rare. The purpose of this study was to evaluate the prognostic and clinical implications of the immunoreactive proteins p53, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 in follicular lymphoma. The material consisted of 67 patients with primarily non-transformed follicular lymphoma. Diagnostic lymph node tissue sections of patients were stained by immunohistochemical method using specific monoclonal antibodies. p53 over-expression was detected in 8 (12%) out of 67 cases. p53 over-expression correlated with high grade (P = 0.011), bulky tumour (P = 0.031) and forthcoming transformation (P = 0.001). It also correlated with poor overall (P = 0.001) and cause-specific survival (P = 0.010) in multivariate analysis and had a strong inverse correlation with time to transformation (P < 0.001). MMP-2, MMP-9 and TIMP-2 expression correlated with high grade. MMP-9 positivity in centroblasts correlated with good chemotherapy response (P = 0.019), but it was not prognostic for survival. MMP-2, TIMP-1 or TIMP-2 did not associate with survival, either. In this study, p53 over-expression predicted both transformation to diffuse large B-cell lymphoma and poorer overall and cause-specific survival of patients with follicular lymphoma. Expression of gelatinases or their inhibitors did not have any significant correlations with prognosis, although MMP-9 predicted a good response to first-line chemotherapy.

Survival Effect of Neoadjuvant Radiotherapy Before Esophagectomy for Patients With Esophageal Cancer: A Surveillance, Epidemiology, and End-Results Study

The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed with NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. </=10), histologic type (adenocarcinoma vs. squamous cell carcinoma), age (<65 vs. >/=65 years), and gender as covariates. A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.

Outcomes following sublobar resection for early-stage non-small cell lung cancer (NSCLC) with or without adjuvant external beam radiation therapy (XRT): A population-based study

7540 Background: Patients undergoing sublobar resection for early stage NSCLC may receive XRT in an effort to improve outcomes despite limited data regarding its efficacy. Methods: Using the Surveillance, Epidemiology and End-Results (SEER) registry we identified patients diagnosed with stage T1–2N0M0 NSCLC between 1988–2003 who were definitively treated with sublobar surgical resection. Patients who refused radiation therapy, received radiation therapy other than XRT, or were coded as unknown regarding radiation treatment were excluded. Kaplan-Meier analysis was performed to compare overall survival (OS) and cause-specific survival (CSS) for patients receiving XRT versus no additional local-regional therapy. Multivariate Cox regression analysis was performed to evaluate the effect of XRT controlling for other covariables. Results: 5,908 eligible patients were identified. 493 received XRT and 5,415 received no additional local-regional treatment. The use of XRT was associated with significantly worse OS and CSS compared with no additional local-regional therapy: 31 and 45 months versus 51 and 98 months, respectively (p<0.001). One, three and five year OS estimates were 78.5%, 43.5%, and 24.5% versus 87.1%, 61.3%, and 43.7%, respectively. On multivariate analysis, the most significant predictor of death was the use of XRT (hazard ratio 1.505, 95% confidence interval 1.318–1.717, p<0.001). Conclusions: The use of adjuvant XRT is associated with a significant decrease in OS and CSS for patients with T1–2N0M0 NSCLC treated with sublobar resection. This may be related to covariables not reported in SEER such as margin status, chemotherapy use, radiation dose and XRT portal. Despite these uncertainties, every effort should be made to avoid combination therapy including XRT in patients not fit for anatomic resection. Alternative treatments such as surgery with wide margins alone, surgery with brachytherapy, or conformal XRT alone should be explored. No significant financial relationships to disclose.

Improved Survival in Patients With Stage III-IV Head and Neck Cancer Treated With Radiotherapy as Primary Local Treatment Modality

To evaluate the overall and cause-specific survival in patients with Stage III-IVb head and neck squamous cell carcinoma treated with radiotherapy (RT) as the primary local treatment modality. The survival of patients with American Joint Committee on Cancer Stage III-IVb head and neck squamous cell carcinoma treated with primary RT was queried using the Surveillance, Epidemiology and End Results database. The effect of the year of treatment on overall and cause-specific survival was analyzed as a categorical and continuous variable. The patterns of care for these patients were also evaluated. Between 1988 and 2004, 6,759 patients were identified. Survival was significantly improved in patients treated more recently. When analyzed as a continuous variable, each year was associated with a 3% and 4.1% reduction in the relative risk of overall and cause-specific mortality, respectively (p < 0.0001). Patients treated after 1998 had a 7.6% and 6.1% absolute improvement in overall and cause-specific survival, respectively, compared with patients treated before 1998 (overall survival, hazard ratio, 0.81; cause-specific survival, hazard ratio, 0.77; p < 0.0001). This benefit in survival was limited to tumors of the oral cavity, oropharynx, and hypopharynx. The use of RT increased among patients treated more recently. This shift in patterns of care was most pronounced for tumors of the larynx and hypopharynx. The overall and cause-specific survival of patients with Stage III-IVb head and neck squamous cell carcinoma treated with primary RT has improved with time. The improvement is consistent with that observed in a large meta-analysis of randomized patients treated with concurrent chemoradiotherapy.

Prostatic Acid Phosphatase Adversely Affects Cause-Specific Survival in Patients with Intermediate to High-Risk Prostate Cancer Treated with Brachytherapy

To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT). From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS. The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393). The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.

Poor prognosis in patients with stage I and II oral tongue squamous cell carcinoma

The objective of this study was to compare survival in patients with squamous cell carcinoma (SCC) of the oral tongue with that in patients with SCC in other oral cavity subsites. Patients with stage I and II (T1-T2N0M0) SCC of the oral cavity diagnosed between 1988 and 2004 were queried by using the Surveillance, Epidemiology, and End Results (SEER) database. The log-rank test was used to compare the overall survival (OS) and cause-specific survival (CSS) of patients who had oral tongue SCC with those of patients who had SCC of other oral cavity subsites. A Cox proportional hazards multivariate analysis was performed to evaluate the influence of covariates on the risk of CSS and OS. Between 1988 and 2004, 6791 patients with stage I and II SCC of the oral cavity were identified. Among them, 40% had oral tongue SCC, and 60% had SCC of other oral cavity subsites. The median patient age was 64 years. The 5-year OS and CSS rates were 60.9% and 83.5%, respectively, for patients with oral tongue SCC versus 64.7% and 94.1%, respectively, for patients with SCC of other oral cavity subsites (OS: hazard ratio, 1.24; P< .0001; CSS: hazard ratio, 3.04; P< .0001). On multivariate analysis, OS and CSS were influenced significantly by T classification, age, sex, and oral tongue subsite. The CSS for patients who had stage I and II oral tongue SCC also was unfavorable compared with the CSS for stage-matched patients who had SCC of other head and neck sites. Oral tongue SCC was associated with poor survival compared with other oral cavity and head and neck sites. These data suggested a potential benefit for multimodality therapy in this cohort of patients.

Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: Results of a study from the surveillance, epidemiology, and end results (SEER) registry data

The role of adjuvant radiation therapy in pancreatic cancer is controversial. For the current study, the authors evaluated the effect of preoperative and postoperative radiation therapy on survival in patients with pancreatic adenocarcinoma. The analysis included 3008 patients who were reported to the Surveillance, Epidemiology, and End Results registry of the National Cancer Institute from 1988 to 2002 who had adenocarcinoma of the pancreas and who underwent cancer-directed surgery. A retrospective analysis of overall survival and cancer-specific survival for these patients was performed using the Kaplan-Meier method. Comparative risks of mortality were evaluated by using multivariate-adjusted Cox regression models. Of 3008 patients, 1267 (42%) received radiation therapy. Overall survival improved significantly in patients who received radiation therapy, with a median survival of 17 months and a 5-year overall survival rate of 13% in patients who received radiation compared with 12 months and 9.7%, respectively, for patients who did not receive radiation therapy (P < .0001). On multivariate analysis, radiation therapy was associated with improvement in overall survival in patients who had direct extension beyond the pancreas and/or regional lymph node involvement (P < .01) but not in patients with T1-T2N0M0 disease (P > .05). Radiation therapy was associated with improvement in cause-specific survival in patients who had regional lymph node involvement (P < .02) but not in patients who had T1-2N0M0 disease or direct extension beyond the pancreas without lymph node involvement (P > .05). Differences in overall and cause-specific survival among patients who received preoperative versus postoperative radiation therapy did not reach statistical significance. Radiation therapy was associated with improved survival compared with cancer-directed surgery without radiation in patients with adenocarcinoma of the pancreas.

Adenocarcinoma (AC) small intestine (SI). Review of prognostic factors and treatment outcomes

15117 Background: AC of SI is a rare disease. Review of 123 cases was done for prognostic factors and treatment outcomes. Methods: Total of 123 cases identified using Saskatchewan Cancer Agency registry. A data collection sheet was generated and chart review was performed. Cause specific survival (CSS) was based on primary cause of death from AC of SI. Survival was calculated using Kaplan Meyer survival curves. P values were calculated using log rank test. Results: CSS of the whole group was 565 days. CSS with no metastatic disease (MD) at presentation was 792 days. 30 patients presented with MD. Patient with MD at presentation who did not receive chemotherapy had a CSS of 83 days. 13 out of 30 patients with MD received 5 flurouracil based chemotherapy. CSS of patients with MD who received chemotherapy was 363 days compared to 83 days who did not receive chemotherapy (p. 0.0036). 11 patients with stage I to III received adjuvant fluropyramidine based chemotherapy. CSS of patients who did not receive adjuvant chemotherapy was 617 days and 52% of patients who received chemotherapy had a survival of 1307 days. There were no further events till 3788 days. CSS for grade 1 tumor was 37.5%, for grade 2 it was 28.9% and 26.4% for Grade 3 tumors. (P value 0.571). 5 year CSS was 15.8% for patients with duodenal involvement 10% for patients with ileal disease and 23.5% for patients with jejunal involvement. (P value 0.415). 5 year CSS with T4 lesions was 18.6% compared to 35% for patients with T3 lesions. (P value 0.077). Patient with node positive disease had 5 years CSS of 11.6% compared to 44.1% with node negative disease. (P value 0.004). Median age at diagnosis was 71 years. CSS of patients with age more than 71 years was 15.3% compared to 19% for less than 71 years of age. (P value .078). Conclusions: Patients who received 5 flurouracil based chemotherapy for MD and in adjuvant setting seems to have better survival outcome. However this may be related to selection bias. Nodal Involvement was associated with poor outcome. Factors as grade of tumor, T stage, age and site of disease involvement were not found to have independent prognostic significance. No significant financial relationships to disclose.

Risk Factors Contributing to a Poor Prognosis of Papillary Thyroid Carcinoma: Validity of UICC/AJCC TNM Classification and Stage Grouping

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

Prognostic Value of Serum β2-Microglobulin in Patients with Waldenström's Macroglobulinemia Requiring Treatment

PurposeWaldenström's macroglobulinemia (WM) is a lymphoplasmacytoid lymphoma characterized by a relatively indolent course with median survival ranging from 5 years to 10 years in different series. Several clinical and laboratory variables have been associated with inferior survival, such as advanced age, hyperviscosity, presence of cytopenia, and hypoalbuminemia. Recent data indicate that serum β-microglobulin (β2M) might also be significant. The purpose of our study was to assess possible correlations of β2M with clinical and laboratory variables and to further evaluate its association with cause-specific and overall survival (OS) of patients with WM requiring treatment. Patients and MethodsWe analyzed 124 patients with WM with an available pretreatment value of β2M. Median age was 70 years (range, 28-89 years), and median survival was 105 months. Multiple clinical and laboratory parameters were evaluated for their possible correlation with OS. ResultsPatients with older age, anemia, thrombocytopenia, hypoalbuminemia, and higher creatinine levels had significantly greater serum β2M levels. This variable was associated with impaired cause-specific survival and OS in the whole group of patients and in patients aged ≤ 70 years. More specifically, OS for all patients according to serum β2M > 4 mg/dL versus ≤ 4 mg/dL was 79 months versus 115 months (P = 0.01). ConclusionOur data provide further evidence that high β2M levels are an important parameter associated with inferior OS and cause-specific survival of patients with WM requiring treatment. This parameter may be used to stratify patients involved in prospective clinical trials.

3–46 Factors Associated With Local Recurrence and Cause-Specific Survival in Patients With Ductal Carcinoma In Situ of the Breast Treated With Breast-Conserving Therapy or Mastectomy

3–46 Factors Associated With Local Recurrence and Cause-Specific Survival in Patients With Ductal Carcinoma In Situ of the Breast Treated With Breast-Conserving Therapy or Mastectomy

Smoking Compromises Cause-specific Survival in Patients with Operable Colorectal Cancer

Aims To assess whether active smoking compromises survival in patients with colorectal cancer. Materials and methods We studied a regionally based cohort of 284 consecutive patients referred to the Tayside Cancer Centre for consideration of adjuvant treatment after curative surgery for colorectal cancer. Results Cause-specific survival was significantly worse ( P = 0.0015) in patients who were actively smoking at the time of their first post-operative visit. The absolute difference in 5-year cause-specific survival (active smokers vs the rest) was 21%. In adjusted multi-variate analysis of patients after pathologically complete (R0) resection, the hazard ratio was 2.55 (95% confidence interval 1.40–4.64) in active smokers compared with non-smokers. T stage, number of positive nodes and co-morbidity score were also of independent prognostic influence. Conclusions Persistent smoking was, in this small series, an important and independent predictor of cancer-related death after surgery for cancer of the large bowel. Because smoking and deprivation are related, some of the adverse effects of deprivation upon survival in this group of patients may be explained by smoking behaviour.

Clinical symptoms in localized renal cell carcinoma reflect its invasive potential: Comparative study between incidentally detected and symptomatic diseases

The objectives of this study were to analyze the association of clinical symptoms with several parameters in patients with organ-confined renal cell carcinoma (RCC), and investigate the difference in biologic characteristics between incidentally detected and symptomatic RCCs. This study included 132 patients who were pathologically diagnosed with organ-confined RCC after radical surgery, and their clinicopathologic features were compared to those in patients with incidentally detected and symptomatic diseases. In this series, 91 patients were incidentally diagnosed with RCC, while the remaining 41 had some clinical symptoms. The cause-specific survival in patients with incidental RCC was significantly higher than that in patients with symptomatic RCC, and the presence of clinical symptoms could be an independent predictor of cause-specific survival in these patients. Immunohistochemical staining of resected specimens from these patients were then performed with Ki-67, Bcl-2, matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor antibodies. Despite the lack of differences in Ki-67, Bcl-2, and vascular endothelial growth factor expression between these 2 groups, significantly increased expressions of MMP-2 and MMP-9 in symptomatic RCCs were observed compared with those in incidental RCCs. Moreover, the presence of clinical symptoms in organ-confined RCC was significantly correlated with immunoreactivities of MMP-2 and MMP-9. These findings suggest that clinical symptoms have a significant impact on the prognosis of patients with organ-confined RCC and that the appearance of clinical symptoms may reflect the increased invasive potentials characterized by overexpression of MMPs.

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.

Expression of CXCR4 and Its Down-Regulation by IFN-γ in Head and Neck Squamous Cell Carcinoma

The functional expression of CXCR4, which plays roles in cell migration and proliferation in response to its unique ligand stromal cell-derived factor-1 (SDF-1), has been reported in variety of carcinomas. However, CXCR4 expression and its functional role in head and neck squamous cell carcinomas (HNSCC) remain unclear. In this study, we investigated CXCR4 expression and analyzed its functions in HNSCC cell lines. We also attempted to regulate CXCR4 expression using cytokines, such as interleukin-1beta, tumor necrosis factor-alpha, and IFN-gamma. Finally, we investigated correlation between CXCR4 expression and clinical features in patients with HNSCC. Six HNSCC cell lines were used in this study. Reverse transcription-PCR and flow cytometry analysis were shown for CXCR4 expressions with or without stimulations of cytokines. SDF-1-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. The SDF-1-mediated cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The SDF-1-mediated signaling pathways were analyzed by Western blot analysis. Biopsy specimens from 56 patients with HNSCC were used for immunohistologic analysis. The significant CXCR4 expression was found in HSQ-89, IMC-3, and Nakamura cells. The SDF-1-mediated cell migration and proliferation were observed in CXCR4-positive cells. SDF-1 also promoted rapid phosphorylation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways in CXCR4-positive cells. The SDF-1-mediated cell migration and proliferation of CXCR4-positive cells were inhibited by neutralization of CXCR4. Among three cytokines tested, IFN-gamma significantly reduced CXCR4 expression and SDF-1-induced cell migration and proliferation of CXCR4-positive cells. Immunohistologic analysis revealed that patients with advanced neck status and patients who developed distant metastases showed significantly higher CXCR4 expression, and the cause-specific survival of patients with CXCR4-expression was significantly shorter. Furthermore, multivariate analysis confirmed that CXCR4 positive was the independent factor for cause-specific death. Our results may provide an insight into future therapeutic agent that inhibits tumor metastasis and progression via down-regulating CXCR4 expression in patients with HNSCC.

The optimum timing of radical cystectomy for patients with recurrent high‐risk superficial bladder tumour

To establish the optimum time of radical cystectomy (RC) for patients with recurrent high-risk superficial bladder tumours after the failure of intravesical therapy. Among 318 patients with transitional cell carcinoma treated with RC and with no neoadjuvant therapy, there were 46 with clinical stage Ta, T1 or Tis refractory to transurethral resection associated with intravesical therapy. These patients had at least one of: (i) high-risk superficial bladder tumours after failure of two consecutive induction courses of intravesical therapy; (ii) superficial bladder tumours with prostatic stromal invasion; (iii) superficial bladder tumours with mucosa/ducts involvement after failure of one course of intravesical therapy; (iv) uncontrolled superficial tumours with transurethral resection associated or not with intravesical therapy. Progression and cause-specific survival of these patients were compared to those with muscle-invasive tumours. Univariate and multivariate analyses of predictive factors for cause-specific survival were also used in patients with superficial tumours. The incidence of significant prognostic factors was compared in both superficial and muscle-invasive tumours, as were the progression pattern and survival. The progression-free and cause-specific survival of patients with superficial tumours was 54% and 67%, respectively, with no significant difference from those with muscle-invasive tumours. In multivariate analysis, positive lymph-nodes and prostatic stromal invasion were significant and independent variables for survival. The incidence of positive lymph nodes was 15% vs 30% (P < 0.05) and of stromal invasion was 32% vs 1.5% (P < 0.001) in patients with superficial and muscle-invasive tumours, respectively. Accounting for the progression pattern in patients with superficial tumours, extravesical urothelial recurrence prevailed over local or distant recurrences (30% vs 15%), whereas in patients with muscle-invasive tumours the opposite occurred (5% vs 33%, respectively). The cause-specific survival of patients with superficial tumour and prostatic stromal invasion was one of three, and in those who developed extravesical urothelial recurrence was 28.5%. In patients with recurrent high-risk superficial bladder cancer after intravesical therapy, our criteria for RC were inappropriate, and patients had a survival rate similar to those with muscle-invasive tumours. RC might have been used too late, as there was a high incidence of prostatic stromal invasion and extravesical urothelial recurrence after RC. Both events seem to be responsible of the low cause-specific survival. Predictive factors for progression are needed to indicate early RC in patients with recurrent high-risk superficial tumours. From a previous analysis the pathological pattern of the clinical lack of response (T1, G3, bladder carcinoma in situ and prostate involvement) to intravesical therapy evaluated at 3 months might be important for predicting progression, and an early RC at that time might be useful.

Long-term outcome by risk factors using conformal high-dose-rate brachytherapy (HDR-BT) boost with or without neoadjuvant androgen suppression for localized prostate cancer

Purpose The aim of this study is to analyze, during the prostate-specific antigen (PSA) era, the long-term outcome of patients treated with conformal high-dose-rate (HDR) brachytherapy boost to the prostate with or without androgen deprivation therapy (ADT) when patients are stratified by risk factors for failure. Methods and materials Between 1986 and 2000, 611 patients were treated for clinically localized prostate cancer in three prospective trials of external beam radiation therapy (EBRT) and dose-escalating HDR brachytherapy (BT) boost. There were 104 patients treated at Seattle, 198 at Kiel University, and 309 at William Beaumont Hospital. Of the 611 patients, 177 received a short course of neoadjuvant/concurrent ADT. The patients were divided into three risk groups. Group I, comprised of 46 patients, had stage ≤T2a, Gleason score (GS) ≤ 6, and initial PSA (iPSA) ≤ 10 ng/mL. Group II comprised 188 patients with stage ≥T2b, GS ≥ 7, and iPSA ≥ 10, with any one factor higher. Group III included 359 patients with any two risk factors higher. The American Society for Therapeutic Radiology and Oncology definition for biochemical failure was used. Results The mean follow-up was 5 years (range, 0.2–15.3). For the 611 patients, the 5-year and 10-year biochemical control (BC) rates were 77% and 73%, disease-free survival (DFS) was 67% and 49%, and cause-specific survival (CSS) was 96% and 92%, respectively. BC at 5 years for Group I patients was 96%, for Group II 88%, and for Group III patients 69%. CSS at 5 years was 100% in Group I, 99% in Group II, and 95% in Group III patients. In univariate and multiple regression analyses for BC, risk group, stage, iPSA, and GS were significant in predicting failure. However, age, follow-up interval, and ADT did not. Conclusions EBRT with HDR-BT produced excellent long-term outcomes in terms of BC, DFS, and CSS in patients with prostate cancer even for those at highest risk. Conformal HDR-BT is both a precise dose delivery system and an effective treatment for both favorable and unfavorable prostate cancer. The addition of a short course of neoadjuvant/concurrent ADT failed to improve outcome. The results were similar at all three institutions, giving credence to the reproducibility of the brachytherapy treatment.

Clinicopathological Features of Incidentally Detected Renal Cell Carcinoma in Japan

Background: The objective of this study was to compare clinical outcomes between patients with symptomatic and incidental renal cell carcinoma (RCC) experienced in a single institution in Japan. Patients and methods: We reviewed the records of 178 consecutive patients who underwent radical or partial nephrectomy for RCC at our institution between April 1984 and March 2002. Several clinicopathological factors of these patients were analyzed according to the mode of presentation at initial diagnosis; that is, symptomatic or incidentally detected RCC. Results: Of the 178 patients, 102 (57.3%) were incidentally discovered. Significant differences between incidental and symptomatic tumors were observed in maximal tumor diameter, distant metastasis, tumorgrade, stage and microscopic venous invasion. Cause-specific survival in patients with incidental tumor was significantly higher than that in those with symptomatic tumor. Moreover, multivariate analysis demonstrated that maximal tumor size, metastasis, and the...

Long-term follow-up of a randomized prospective trial comparing a standard 81mg dose of intravesical bacille calmette-guérin with a reduced dose of 27mg in superficial bladder cancer. : BJU Int 2002;89:671–680.

Objectives: To determine the efficacy of a three-fold reduced dose (RD, 27 mg) of intravesical bacille Calmette-Guérin (BCG) against the standard dose (81 mg) in patients with superficial bladder cancer, assessing recurrence, progression, and differences in toxicity. Patients and Methods: Five hundred patients with superficial bladder cancer (Ta, T 1, Tis) were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG Connaught strain (weekly × six and thereafter fortnightly × six) either with the standard or RD instillation. Results: All but one of the 500 patients were evaluable for efficacy and toxicity (252 in the standard arm and 247 in the RD arm). The median follow-up was 69 months (maximum 104); 71 (28%) patients in the standard arm and 76 (31%) in the RD arm developed recurrences; the median time to recurrence has not yet been attained, but at 5 years the mean (sd) percentage of recurrence-free patients was 70.5 (3.12) and 70.4 (3.1) for the standard and RD arms, respectively. In patients presenting with multifocal tumours, the standard dose was more effective against recurrences than the RD ( P = 0.0151). In those with G3 and high-risk tumours overall, the superiority of the standard dose was marginal ( P = 0.060 and P = 0.082). Twenty-nine (11.5%) tumours in the standard arm and 33 (13.3%) in the RD arm progressed to invasive disease; the median time to progression has not yet been attained, but the percentage of progression-free patients at 5 years was 88.8 (2.23) and 86.9 (2.31) for the standard and RD arms, respectively. The standard dose was more effective than the RD against progression only in patients with multifocal disease ( P = 0.048). Twelve (4.8%) cystectomies were performed in the standard and 15 (6.1%) in the RD arm. Currently, 106 (21.2%) patients have died, but only 38 (7.6%) from bladder cancer, i.e., 20 (7.9%) in the standard and 18 (7.5%) in RD arm. Overall the disease-specific death rate was lower for those patients who completed the scheduled treatment. The cause-specific survival at 5 years did not differ between the arms ( P = 0.76) but there was a trend toward better cause-specific survival for patients with multifocal tumours in the standard arm. Toxicity differed between the arms, significantly more patients having no toxicity in the RD arm, and fewer having delayed instillations or withdrawing. However, severe systemic toxicity occurred even in patients treated with the RD, in a similar proportion to those receiving the standard dose. Conclusion: Overall, the RD gave similar results for recurrence and progression but with significantly less toxicity. However, patients with multifocal tumours fared better with the standard dose and there was a trend towards better recurrence rates in patients with high-risk tumours. We recommend continuing to use the standard dose for high-risk tumours, whereas we consider the RD safe and effective for intermediate-risk lesions and for maintenance schedules.

The effect of overall treatment time on the survival and toxicity of radical radiotherapy for cervical carcinoma

Background and purpose: Overall treatment time is an important factor in the outcome of radical radiotherapy in head and neck, bladder and lung cancer and in cervix cancer treated over more than 7 weeks. This study analysed the effect of prolongation of overall treatment time on survival and late morbidity for patients receiving radical radiotherapy for cervical cancer treated with a 4-week regimen. Materials and methods: Using the departmental SAS data-base we identified all patients with cervix cancer treated between 1974 and 1988 and investigated the 647 patients who received 20 fractions of external beam radiotherapy plus intracavitary therapy with a total dose to point A of at least 60 Gy. A retrospective case-note review identified tumour and treatment-related variables. Results: Four hundred and twenty-five (66%) patients had at least one gap in treatment. Seventy-nine gaps (11%) were due to unavoidable patient or treatment-related causes. We could not find an effect of a treatment gap ( P=0.43) or an increased overall treatment time ( P=0.79) on the cause specific survival of patients. There was significantly more grade 4 morbidity in those patients treated over a short period (29–32 days) compared to the rest ( P=0.005), possibly related to the loss of radiotherapy-free days to weekend intracavitary insertions. Conclusions: We could not demonstrate a significant effect of overall treatment time in this series of patients, almost all of whom were treated in less than 7 weeks. Those patients treated over the shortest period had an increased incidence of late morbidity.