Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia.

In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678.

Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML.

Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukaemia (CML) indicate an increased risk of progression and shorter survival. Since major route ACA are almost always unbalanced, it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis. On the basis of 1348 Philadelphia chromosome-positive chronic phase patients of the randomized CML study IV, we examined the impact of unbalanced minor route ACA at diagnosis versus major route ACA on prognosis. At diagnosis, 1175 patients (87.2 %) had a translocation t(9;22)(q34;q11) and 74 (5.5 %) a variant translocation t(v;22) only, while a loss of the Y chromosome (-Y) was present in addition in 44 (3.3 %), balanced or unbalanced minor route ACA each in 17 (1.3 %) and major route ACA in 21 (1.6 %) cases. Patients with unbalanced minor route ACA had no significantly different cumulative incidences of complete cytogenetic remission or major molecular remission and no significantly different progression-free survival (PFS) or overall survival (OS) than patients with t(9;22), t(v;22), -Y and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (all pairwise comparisons to each of the other groups: p ≤ 0.015). Five-year survival probabilities were for t(9;22) 91.4 % (95 % CI 89.5-93.1), t(v; 22) 87 % (77.2-94.3), -Y 89.0 % (76.7-97.0), balanced 100 %, unbalanced minor route 92.3 % (72.4-100) and major route 52.2 % (28.2-75.5). We conclude that only major route, but not balanced or unbalanced minor route ACA at diagnosis, has a negative impact on prognosis of CML.

Gamma Knife Surgery versus Linac for Brain Metastasis: Which Technique for Which Patient? Analysis of an Historical Cohort of 63 Consecutive Patients Harboring 130 Lesions

Objectives: We present the retrospective analysis of a single-institution experience for radiosurgery (RS) in brain metastasis (BM) with Gamma Knife (GK) and Linac. Methods: From July 2010 to July 2012, 28 patients (with 83 lesions) had RS with GK and 35 patients (with 47 lesions) with Linac. The primary outcome was the local progression-free survival (LPFS). The secondary outcome was the overall survival (OS). Apart a standard statistical analysis, we included a Cox regression model with shared frailty, to modulate the within-patient correlation (preliminary evaluation showed a significant frailty effect, meaning that the correlation within patient could be ignored). Results: The mean follow-up period was 11.7 months (median 7.9, 1.7-22.7) for GK and 18.1 (median 17, 7.5-28.7) for Linac. The median number of lesions per patient was 2.5 (1-9) in GK compared with 1 (1-3) in Linac. There were more radioresistant lesions (melanoma) and more lesions located in functional areas for the GK group. The median dose was 24 Gy (GK) compared with 20 Gy (Linac). The LPFS actuarial rate was as follows: for GK at 3, 6, 9, 12, and 17 months: 96.96, 96.96, 96.96, 88.1, and 81.5%, and remained stable till 32 months; for Linac at 3, 6, 12, 17, 24, and 33 months, it was 91.5, 91.5, 91.5, 79.9, 55.5, and 17.1%, respectively (p = 0.03, chi-square test). After the Cox regression analysis with shared frailty, the p-value was not statistically significant between groups. The median overall survival was 9.7 months for GK and 23.6 months for Linac group. Uni- and multivariate analysis showed a lower GPA score and noncontrolled systemic status were associated with lower OS. Cox regression analysis adjusting for these two parameters showed comparable OS rate. Conclusions: In this comparative report between GK and Linac, preliminary analysis showed that more difficult cases are treated by GK, with patients harboring more lesions, radioresistant tumors, and highly functional located. The groups look, in this sense, very heterogeneous at baseline. After a Cox frailty model, the LPFS rates seemed very similar (p < 0.05). The OS was similar, after adjusting for systemic status and GPA score (p < 0.05). The technical reasons for choosing GK instead of Linac were the anatomical location related to highly functional areas, histology, technical limitations of Linac movements, especially lower posterior fossa locations, or closeness of multiple lesions to highly functional areas optimal dosimetry with Linac

Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04.

Aim: We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP. Methods: Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research Results: Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3-10.7) and median OS was 15.0 (95% CI: 12.1-19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5-10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0-17.6) months. Conclusions: This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP. Disclosure: All authors have declared no conflicts of interest.

Final results of the SAKK 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 non-small cell lung cancer (NSCLC).

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Poorly differentiated clusters (PDC) in colorectal cancer: what is and ought to be known.

BACKGROUND: The counting of poorly differentiated clusters of 5 or more cancer cells lacking a gland-like structure in a tumor mass has recently been identified among the histological features predictive of poor prognosis in colorectal cancer. MAIN BODY: Poorly differentiated clusters can easily be recognized in the histological sections of colorectal cancer routinely stained with haematoxylin and eosin. Despite some limitations related to specimen fragmentation, counting can also be assessed in endoscopic biopsies. Based on the number of poorly differentiated clusters that appear under a microscopic field of a ×20 objective lens (i.e., a microscopic field with a major axis of 1 mm), colorectal cancer can be graded into malignancies as follows: tumors with <5 clusters as grade 1, tumors with 5 to 9 clusters as grade 2, and tumors with ≥10 clusters as grade 3. High poorly differentiated cluster counts are significantly associated with peri-neural and lympho-vascular invasion, the presence of nodal metastases or micrometastases, as well as shorter overall and progression free survival to colorectal cancer. CONCLUSION: The morphological aspects and clinical relevance of poorly differentiated clusters counting in colorectal cancer are discussed in this review.

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL).

BACKGROUND: Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed. PATIENTS AND METHODS: The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors. RESULTS: With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS. CONCLUSION: TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

Locally advanced hypopharyngeal squamous cell carcinoma: single-institution outcomes in a cohort of patients curatively treated either with or without larynx preservation

Abstract Objective: The present study was aimed at describing a single-institution experience in the curative treatment of patients diagnosed with locally advanced hypopharyngeal squamous cell carcinoma. Materials and Methods: Data concerning all patients treated for locally advanced hypopharyngeal squamous cell carcinoma between January 2006 and June 2012 were reviewed. Results: A total of 144 patients were included in the present study. The median follow-up period was 36.6 months. Median survival was 26 months, and 2-year and 5-year overall survival rates were, 51% and 30.5%, respectively. Median recurrence-free survival was 18 months and 2-year and 5-year recurrence-free survival rates were 42.8% and 28.5%, respectively. Conclusion: The outcomes in the present series are in line with the literature.

Statistical Analysis of an SEIR Epidemic Model

This thesis was focussed on statistical analysis methods and proposes the use of Bayesian inference to extract information contained in experimental data by estimating Ebola model parameters. The model is a system of differential equations expressing the behavior and dynamics of Ebola. Two sets of data (onset and death data) were both used to estimate parameters, which has not been done by previous researchers in (Chowell, 2004). To be able to use both data, a new version of the model has been built. Model parameters have been estimated and then used to calculate the basic reproduction number and to study the disease-free equilibrium. Estimates of the parameters were useful to determine how well the model fits the data and how good estimates were, in terms of the information they provided about the possible relationship between variables. The solution showed that Ebola model fits the observed onset data at 98.95% and the observed death data at 93.6%. Since Bayesian inference can not be performed analytically, the Markov chain Monte Carlo approach has been used to generate samples from the posterior distribution over parameters. Samples have been used to check the accuracy of the model and other characteristics of the target posteriors.

Salivary gland cancer in Finland: Incidence, histological distribution, outcome and prognostic factors

Salivary gland cancer (SGC) is a rare cancer. The histological classification of SGC is complex and its biological behavior highly variable: it may vary from a low-grade tumor to a high-grade and often fatal malignancy. These circumstances make this cancer a diagnostic and therapeutic challenge. Older age and exposure to ionizing radiation are known risk factors. The mainstay of treatment is surgery combined with adjuvant radiation therapy, when appropriate. In addition to the histological type, the only well known prognostic factor is the TNM classification, which describes the tumor size and the amount of metastases. This study was performed using a full population-based nationwide cohort of SGC patients and tumors diagnosed in Finland in 1991-1996. The annual incidence of SGC in the entire population was, on average, 47.7 per year. By histological re-evaluation of 237 specimens the most frequent histological types were the adenoid cystic carcinoma (n=65; 27%), the mucoepidermoid carcinoma (n=45; 19%) and the acinic cell carcinoma (n=41; 17%). The highest 10-year disease-specific survival rate occurred among patients with acinic cell carcinoma (90%), followed by mucoepidermoid carcinoma (81%) and adenoid cystic carcinoma (60%). A high volume-corrected index (VCI) of Ki-67 correlated with worse survival of patients with SGC. Computer-assisted morphometric analyses of CD34-positive vessels indicated an unfavorable prognosis for patients with mucoepidermoid carcinoma and an association with poor survival among patients with acinic cell carcinoma. A high level of expression of matrix metalloproteinase-9 (MMP-9) showed a trend for a poorer prognosis in salivary duct carcinoma, and a high level of MMP-13 and a low level of MMP-1 had a trend for a poorer prognosis of patients with SGC. A low level of MMP-7 was associated with a poor prognosis of patients with acinic cell and mucoepidermoid carcinoma.

Linfoma esofágico primário

We describe the case of a 54 year old woman seen with an esophageal mass diagnosed as a primary esophageal lymphoma. The main symptom was dysphagia of seven months duration. The treatment consisted in resection of the tumor, and reconstruction of the defect with a reversed pleural flap, followed by a chemotherapy regimen that consisted of five drugs, cyclophosphamid, prednisone, doxorubicin, rituximab and vincristine (R-CHOP). The patient developed an esophageal pleural fistula treated with pleural drainage and irrigation that closed in 45 days. Two and one half years later she is doing well and disease free.

Fatigue and quality of life in breast cancer survivors: a comparative study

PURPOSE: To assess fatigue and quality of life in disease-free breast cancer survivors in relation to a sample of age-matched women with no cancer history and to explore the relationship between fatigue and quality of life.METHODS: A cross-sectional study was conducted in a sample of 202 consecutive disease-free Brazilian breast cancer survivors, all of whom had completed treatment, treated at 2 large hospitals. The patients were compared to age-matched women with no cancer history attending a primary health care center. The Piper Fatigue Scale-Revised and the World Health Organization Quality of Life Instrument (WHOQOL-BREF) were used to measure the fatigue and quality of life, respectively. Socio-demographic and clinical variables were also obtained. The χ2 test, generalized linear model, and Spearman correlation coefficient were used for statistical purposes. The adopted level of significance was 5%.RESULTS: Breast cancer survivors experienced significantly greater total and subscale fatigue scores than comparison group (all p-values<0.05). In addition, survivors reported a poorer quality of life in physical (p=0.002), psychological (p=0.03), and social relationships (p=0.03) domains than comparison group. No difference was found for the environmental domain (p=0.08) for both groups. For survivors of breast cancer and for comparison group, the total and subscale fatigue scores were related to lower quality of life (all p-values<0.01).CONCLUSION: The findings of this study highlight the importance of assessing fatigue and quality of life in breast cancer survivors.

Serodiagnosis of Babesia equi in horses submitted to exercise stress

A complement fixation test (CFT), performed in microtitre plates, based upon the use of crude antigenic preparation of Babesia equi was adapted for the detection of antibodies in serum of infected horses. The indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) were also used for the immunodiagnosis of B. equi. Serum samples from 15 apparently healthy horses, previously conditioned to a high-speed equine treadmill, were taken before and after exercise. All the samples analyzed were positive for B. equi infection. There were no significant differences (P<0.01) between these 3 tests, or the condition of rest or stress. The combined use of CFT and IFAT or ELISA should be recommended in order to enable veterinary services to more efficiently prevent introduction of infected horses into disease-free areas.

The Effects of the Breast Cancer Mammography Screening Programme in Women aged 40 to 84 years in Turku, Finland (1987-2009)

The objective of this thesis was to evaluate whether a more extensive mammography screening programme (TurkuMSP) conducted by the city of Turku, had an effect on breast cancer (BC) incidence, survival, or mortality in years 1987 to 2009. Despite the fact that some studies have suggested a 20 percent reduction in BC mortality due to mammography screening, there are findings of harm to subjects, which are claimed to negate the benefits of screening. Thus, the aims of this study are most pertinent. A total of 176 908 screening examinations were performed in 36 000 women aged 40−74 during the years 1987−1997. In all, 685 primary BCs were found in the screened women, either screen-detected (n=531) or during screening intervals (n=154). Survival and BC recurrence rate of women with screen-detected BC was compared to 184 women with clinical BCs detected among individuals who did not take part in the screening. The invitation interval, which may influence the outcome, was studied in the age group 40 to 49 by inviting those born in even calendar years annually for mammography screening and those born in odd years, triennially. In addition, BC incidence and mortality in the total female population of Turku aged 40 to 84 years was compared with the respective figures of Helsinki and the rest of Finland, both during the pre-screening era (1976-1986) and the screening era (1987-2009). The study was designed to compare women by age groups, because women aged 50 to 59 were generally screened in all of Finland, whereas only in Turku women aged 40 to 49 and 60 to 74 were screened in addition. Data regarding cancer recurrence were derived from the Finnish Cancer Registry and data on deaths were collected from Statistics Finland. In survival analyses, screened women with invasive BC had a significantly higher survival rate than the women with clinical BC. The survival benefit started to appear already during the first follow-up years and was evident in all age groups. A marginal survival extension was also seen in screened women when BC had spread to ipsilateral axillary nodes already at diagnosis. Recurrence-free survival rate after BC treatment was significantly more favorable among the screened women compared with women with BC found clinically. The screening invitation interval did not significantly influence BC mortality in the subset of women aged 40 to 49 years. There were no consistent differences in the changes of BC incidence between Turku and the comparison areas during the screening era. In Turku, the BC mortality incidence in women aged 55−69 years was significantly lower during the screening era (from 1987 to 1997) compared with the pre-screening era, whereas no such change was found in the city of Helsinki or Tampere. When comparing the changes in incidence-based BC mortality during years 1987 to 2009 in Turku to those of Helsinki and the rest of Finland, there was a suggestion of more than 20 percent lower mortality in Turku among oldest age group (75-84 years) compared with the reference residential areas, but the differences were not consistently significant. Interpretation of the study results should be made with caution because there were no random control groups, and on the other hand, the number of cases in subgroups was fairly low to yield definite conclusions. Also due to the many statistical analyses, some of the findings may be due to chance. The results are, however, suggestive for a decrease of BC mortality in the elderly age groups due to wide mammography screening. This finding needs confirmation in further studies before recommending an expansion of mammography screening to women up to the age of 74 years

Multiple factor analysis of metachronous upper urinary tract transitional cell carcinoma after radical cystectomy

Transitional cell carcinoma (TCC) of the urothelium is often multifocal and subsequent tumors may occur anywhere in the urinary tract after the treatment of a primary carcinoma. Patients initially presenting a bladder cancer are at significant risk of developing metachronous tumors in the upper urinary tract (UUT). We evaluated the prognostic factors of primary invasive bladder cancer that may predict a metachronous UUT TCC after radical cystectomy. The records of 476 patients who underwent radical cystectomy for primary invasive bladder TCC from 1989 to 2001 were reviewed retrospectively. The prognostic factors of UUT TCC were determined by multivariate analysis using the COX proportional hazards regression model. Kaplan-Meier analysis was also used to assess the variable incidence of UUT TCC according to different risk factors. Twenty-two patients (4.6%). developed metachronous UUT TCC. Multiplicity, prostatic urethral involvement by the bladder cancer and the associated carcinoma in situ (CIS) were significant and independent factors affecting the occurrence of metachronous UUT TCC (P = 0.0425, 0.0082, and 0.0006, respectively). These results were supported, to some extent, by analysis of the UUT TCC disease-free rate by the Kaplan-Meier method, whereby patients with prostatic urethral involvement or with associated CIS demonstrated a significantly lower metachronous UUT TCC disease-free rate than patients without prostatic urethral involvement or without associated CIS (log-rank test, P = 0.0116 and 0.0075, respectively). Multiple tumors, prostatic urethral involvement and associated CIS were risk factors for metachronous UUT TCC, a conclusion that may be useful for designing follow-up strategies for primary invasive bladder cancer after radical cystectomy.