D N Mohr, K P Offord, R A Owen, L J Melton
Asymptomatic microhematuria and urologic disease. A population-based study.
JAMA. 1986 Jul 11;256(2):224-9.
Abstract/Text
Asymptomatic microhematuria is a common finding, occurring in 13% of adult men and postmenopausal women in Rochester, Minn. Previous recommendations to perform cystoscopic and excretory urographic examinations on all patients with this finding were based on findings in referred patients. In the present population-based study, the frequency of serious urologic disease in patients with asymptomatic microhematuria was 2.3%; only 0.5% had bladder or renal cell carcinoma. Urologic malignant lesions occurred more frequently in the elderly. There was a trend toward more serious diseases in those with higher grades of hematuria. Complete urologic investigation of all patients with any degree of asymptomatic microhematuria cannot be recommended. The presence of other risk factors should be considered in opting for further evaluation.
J M Kaldor, N E Day, B Kittelmann, F Pettersson, F Langmark, D Pedersen, P Prior, F Neal, S Karjalainen, J Bell
Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study.
Int J Cancer. 1995 Sep 27;63(1):1-6.
Abstract/Text
A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.
J O Barentsz, J A Witjes, J H Ruijs
What is new in bladder cancer imaging.
Urol Clin North Am. 1997 Aug;24(3):583-602.
Abstract/Text
Treatment and prognosis of urinary bladder cancer largely are determined by the tumor stage and presence of metastases. MR imaging and clinical staging complement each other. MR imaging is the most accurate technique for differentiating the various stages of deep tumor infiltration and detection of metastases, whereas clinical staging is the best technique for differentiating between postbiopsy effects and the various stages of superficial tumors. The role of MR imaging in staging of this disease and monitoring of therapy is reviewed and illustrated. Finally, the authors present an overview of current and future applications of this technique.
日本泌尿器科学会、日本病理学会、日本医学放射線学会編：腎盂・尿管・膀胱癌取扱い規約、金原出版、2011.
Eiji Satoh, Noriomi Miyao, Hitoshi Tachiki, Yasunori Fujisawa
Prediction of muscle invasion of bladder cancer by cystoscopy.
Eur Urol. 2002 Feb;41(2):178-81.
Abstract/Text
OBJECTIVES: Urologists make a decision on whether to indicate staging procedures for primary lesions of bladder cancer by findings of cystoscopy. However, cystoscopic findings for prediction of muscle-invasive bladder cancer have not been fully evaluated.
METHODS: Two hundred seventy consecutive events of 165 patients with bladder cancer were included in this study. Multivariate analysis by a logistic regression model was applied to analyze cystoscopic findings for prediction of muscle invasion of bladder cancer.
RESULTS: Logistic regression analysis revealed that the size, stalk and configuration of the cancer were independent and significant factors that predict muscle invasion of bladder cancer.
CONCLUSIONS: Cystoscopic findings of bladder cancer may predict muscle invasion. When invasion is suggested by cystoscopy, imaging studies may be necessary before TUR of the cancer as well as deep resection of it.
J P Stein, G Lieskovsky, R Cote, S Groshen, A C Feng, S Boyd, E Skinner, B Bochner, D Thangathurai, M Mikhail, D Raghavan, D G Skinner
Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.
J Clin Oncol. 2001 Feb 1;19(3):666-75.
Abstract/Text
PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes.
PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients.
RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence.
CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.
C N Sternberg, A Yagoda, H I Scher, R C Watson, H W Herr, M J Morse, P C Sogani, E D Vaughan, N Bander, L R Weiselberg
M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium.
J Urol. 1988 Mar;139(3):461-9.
Abstract/Text
Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.
D F Bajorin, P M Dodd, M Mazumdar, M Fazzari, J A McCaffrey, H I Scher, H Herr, G Higgins, M G Boyle
Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy.
J Clin Oncol. 1999 Oct;17(10):3173-81.
Abstract/Text
PURPOSE: The variation in reported survival of patients with metastatic transitional-cell carcinoma (TCC) treated with systemic chemotherapy may be a consequence of pretreatment patient characteristics. We hypothesized that a prognostic factor-based model of survival among patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy could account for such differences and help guide clinical trial design and interpretation.
PATIENTS AND METHODS: A database of 203 patients with unresectable or metastatic TCC was retrospectively subjected to a multivariate regression analysis to determine which patient characteristics had independent prognostic significance for survival. Patients were assigned to three risk categories depending on the number of unfavorable characteristics. Patient selection in phase II studies was addressed by developing a table of expected median survival for patient cohorts that had varying proportions of patients from the three risk categories.
RESULTS: Two factors had independent prognosis: Karnofsky performance status (KPS) less than 80% and visceral (lung, liver, or bone) metastasis. Median survival times for patients who had zero, one, or two risk factors were 33, 13.4, and 9.3 months, respectively (P =.0001). The median survival time of patient cohorts could vary from 9 to 26 months simply by altering the proportion of patients from different risk categories.
CONCLUSION: The presence of baseline KPS less than 80% or visceral metastasis has an impact on survival. Reporting the proportion of patients with zero, one, and two risk factors will facilitate understanding of the relevance of the median survival in phase II trials. Phase III trials should stratify patients according to the number of risk factors to avoid imbalance in treatment arms.
Sivaprakasam Sivalingam, John L Probert, Hartwig Schwaibold
The role of repeat transurethral resection in the management of high-risk superficial transitional cell bladder cancer.
BJU Int. 2005 Oct;96(6):759-62. doi: 10.1111/j.1464-410X.2005.05710.x.
Abstract/Text
Advanced Bladder Cancer Meta-analysis Collaboration
Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis.
Lancet. 2003 Jun 7;361(9373):1927-34.
Abstract/Text
BACKGROUND: Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease.
METHODS: We analysed updated data for 2688 individual patients from ten available randomised trials.
FINDINGS: Platinum-based combination chemotherapy showed a significant benefit to overall survival (combined hazard ratio [HR] 0.87 [95% CI 0.78-0.98, p=0.016]; 13% reduction in risk of death; 5% absolute benefit at 5 years [1-7]; overall survival increased from 45% to 50%). This effect was observed irrespective of the type of local treatment, and did not vary between subgroups of patients. The HR for all trials, including those using single-agent cisplatin, tended to favour neoadjuvant chemotherapy (HR=0.91, 95% CI 0.83-1.01) although this tendency was not significant (p=0.084). Although platinum based combination chemotherapy was beneficial, there was no evidence to support the use of single-agent platinum; indeed, there was a significant difference in the effect between these groups of trials (p=0.044).
INTERPRETATION: This improvement in survival encourages the use of platinum-based combination chemotherapy for patients with invasive bladder cancer.
Watanabe E. et al. Cancer Immunol. Immunother. 52: 481-6, 2003.
日本泌尿器科学会編：膀胱癌診療ガイドライン 2009年版、医学図書出版、2009.
Claus Rödel, Gerhard G Grabenbauer, Reinhard Kühn, Thomas Papadopoulos, Jürgen Dunst, Martin Meyer, Karl M Schrott, Rolf Sauer
Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results.
J Clin Oncol. 2002 Jul 15;20(14):3061-71.
Abstract/Text
PURPOSE: To evaluate our long-term experience with combined modality treatment and selective bladder preservation and to identify factors that may predict treatment response, risk of relapse, and survival.
PATIENTS AND METHODS: Between 1982 and 2000, 415 patients with bladder cancer (high-risk T1, n = 89; T2 to T4, n = 326) were treated with radiotherapy (RT; n = 126) or radiochemotherapy (RCT; n = 289) after transurethral resection (TUR) of the tumor. Six weeks after RT/RCT, response was evaluated by restaging-TUR. In case of complete response (CR), patients were observed at regular intervals. In case of persistent or recurrent invasive tumor, salvage-cystectomy was recommended. Median follow-up was 60 months (range, 6 to 199 months).
RESULTS: CR was achieved in 72% of patients. Local control after CR without muscle-invasive relapse was maintained in 64% of patients at 10 years. Distant metastases were diagnosed in 98 patients with an actuarial rate of 35% at 10 years. Ten-year disease-specific survival was 42%, and more than 80% of survivors preserved their bladder. Early tumor stage and a complete TUR were the most important factors predicting CR and survival. RCT was more effective than RT alone in terms of CR and survival. Salvage cystectomy for local failure was associated with a 45% disease-specific survival rate at 10 years. Cystectomy because of a contracted bladder was restricted to 2% of patients.
CONCLUSION: TUR with RCT is a reasonable option for patients seeking an alternative to radical cystectomy. Ideal candidates are those with early-stage and unifocal tumors, in whom a complete TUR is accomplished.
Takahiko Hara, Jun Nishijima, Yoshihiro Miyachika, Yoshiaki Yamamoto, Shigeru Sakano, Hideyasu Matsuyama
Primary cT2 bladder cancer: a good candidate for radiotherapy combined with cisplatin for bladder preservation.
Jpn J Clin Oncol. 2011 Jul;41(7):902-7. doi: 10.1093/jjco/hyr064. Epub 2011 May 25.
Abstract/Text
BACKGROUND: Bladder preservation therapy (BPT) has been attempted for patients with localized muscle-invasive bladder cancer. However, the indication for BPT has not yet been established. To identify patients who are good candidates for BPT, we evaluated our long-term experience with chemoradiation therapy (CRT) for bladder preservation.
METHODS: Between 1994 and 2009, 82 patients with bladder cancer (clinical stage T2-N0M0) without concurrent upper urinary tract urothelial cancer were treated with CRT. Before CRT, the patients had a biopsy or resection of the tumor by transurethral resection (TUR). The response to CRT was evaluated by TUR, urine cytology and computed tomography.
RESULTS: Thirty-two cases (39.0%) had a pathological complete response (pCR) that was defined as no microscopic residual tumor in the bladder. After TUR, 69 cases (84.0%) achieved local control of the cancer, which was considered as a clinical complete response (cCR). There was no significant association between achievement of pCR and examined parameters. The long-term results of CRT were evaluated in cCR cases. The median follow-up was 42.8 months (range, 4.1-155.1). The 5-year overall survival rate was 77.7% and 5-year progression-free survival rate was 64.5%. Clinical T stage and type of tumor (primary or recurrence) were predictive factors for overall survival as well as progression-free survival. In addition, primary cT2 cases had significantly better prognosis than cT3-4 and recurrent cases in overall survival and progression-free survival (P= 0.008 and P= 0.046, respectively).
CONCLUSION: Cases with a primary cT2 tumor could be good candidates for BPT with radiation combined with cisplatin.
H von der Maase, S W Hansen, J T Roberts, L Dogliotti, T Oliver, M J Moore, I Bodrogi, P Albers, A Knuth, C M Lippert, P Kerbrat, P Sanchez Rovira, P Wersall, S P Cleall, D F Roychowdhury, I Tomlin, C M Visseren-Grul, P F Conte
Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study.
J Clin Oncol. 2000 Sep;18(17):3068-77.
Abstract/Text
PURPOSE: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium.
PATIENTS AND METHODS: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8 and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles.
RESULTS: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively), and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue.
CONCLUSION: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.
David J Vaughn
Moving forward in advanced bladder cancer.
J Clin Oncol. 2007 Jun 1;25(16):2162-3. doi: 10.1200/JCO.2006.10.3630.
Abstract/Text
Harry W Herr, James R Faulkner, H Barton Grossman, Ronald B Natale, Ralph deVere White, Michael F Sarosdy, E David Crawford
Surgical factors influence bladder cancer outcomes: a cooperative group report.
J Clin Oncol. 2004 Jul 15;22(14):2781-9. doi: 10.1200/JCO.2004.11.024. Epub 2004 Jun 15.
Abstract/Text
PURPOSE: A randomized, cooperative group trial (Southwest Oncology Group 8710, Intergroup 0080) reported that neoadjuvant chemotherapy improved the survival of patients with locally advanced bladder cancer who were treated with radical cystectomy. We evaluated whether surgical factors from patients enrolled onto the study predicted bladder cancer outcomes.
PATIENTS AND METHODS: Surgical and tumor factors were recorded from surgical and pathologic reports from 268 patients with muscle-invasive bladder cancer who received radical cystectomy. Cystectomies were performed by 106 surgeons in 109 institutions. Half of the patients received neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy. Variables were tested in univariate and multivariate analyses for associations with postcystectomy survival (PCS) and local recurrence (LR) in all patients receiving cystectomy.
RESULTS: Five-year PCS and LR rates were 54% and 15%, respectively. A multivariate model adjusted for MVAC (P =.97), age (P =.03), pathologic stage (P =.0002), and node status (P =.04) showed that surgical variables associated with longer PCS were negative margins (v positive; hazard ratio [HR], 0.37; P =.0007), and > or = 10 nodes removed (v < 10; HR, 0.51; P =.0001). These associations did not differ by treatment arms (P >.21 for all tests of interactions between treatment and surgical variables). Predictors of LR in a multivariate model adjusted for MVAC (P =.16), pathologic stage (P =.02), and node status (P =.37) were positive margins (v negative; odds ratio [OR], 11.2; P =.0001) and fewer than 10 nodes removed (v > or = 10; OR, 5.1; P =.002).
CONCLUSION: Surgical factors influence bladder cancer outcomes after cystectomy, after adjustment for pathologic factors and neoadjuvant chemotherapy usage.
Michael P Porter, David F Penson
Health related quality of life after radical cystectomy and urinary diversion for bladder cancer: a systematic review and critical analysis of the literature.
J Urol. 2005 Apr;173(4):1318-22. doi: 10.1097/01.ju.0000149080.82697.65.
Abstract/Text
PURPOSE: Continent forms of urinary diversion have become a gold standard of urinary tract reconstruction after radical cystectomy, based mostly on the premise of improved quality of life. It is unclear whether the existing body of literature supports this assumption.
MATERIALS AND METHODS: We performed a systematic review to determine if differences exist in health related quality of life (HRQOL) outcomes among different types of urinary diversion after radical cystectomy. A MEDLINE search was performed inclusive of the dates 1966 to January 2004. Inclusion criteria included adult patients, patients with bladder cancer, comparative studies, original research, primary study outcome related to quality of life, and use of a quality of life instrument to measure outcomes. Only studies comparing neobladder, continent reservoir, or conduit diversion were included.
RESULTS: Of 378 initial articles 15 studies met all inclusion criteria. None of the studies were randomized trials. Only 1 study was prospective. Of 15 studies 10 (67%) used some type of previously validated HRQOL instrument, 10 (67%) used some form of ad hoc instrument, 11 (73%) used bladder cancer disease specific instruments, while 9 (60%) used general instruments. Only 1 of the bladder cancer specific instruments had been previously validated. Common limitations included unvalidated HRQOL instruments, use of general HRQOL instruments only, lack of baseline data, cross- sectional analysis, and retrospective study design.
CONCLUSIONS: To date, the current body of published literature is insufficient to conclude that 1 form of urinary diversion is superior to another based on HRQOL outcomes. Future studies should attempt to incorporate prospective data collection, longer term followup and validated disease specific HRQOL instruments.
Wassim Kassouf, David Swanson, Ashish M Kamat, Dan Leibovici, Arlene Siefker-Radtke, Mark F Munsell, H Barton Grossman, Colin P N Dinney
Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the M. D. Anderson Cancer Center experience.
J Urol. 2006 Jun;175(6):2058-62. doi: 10.1016/S0022-5347(06)00322-3.
Abstract/Text
PURPOSE: Partial cystectomy is a surgical option for select patients diagnosed with urothelial carcinoma. We review our experience with partial cystectomy for muscle invasive urothelial carcinoma to assess local control and survival rates.
MATERIAL AND METHODS: From 1982 to 2003 a total of 37 patients with muscle invasive urothelial carcinoma underwent partial cystectomy with curative intent. Reviewed data included history of superficial tumors, presence of variant histology, tumor location, clinical stage, pathological stage, presence of carcinoma in situ, adjuvant therapy and disease status.
RESULTS: The 5-year overall, disease specific and recurrence-free survival rates were 67%, 87% and 39%, respectively. Mean followup was 72.6 months (range 6 to 217). Of the 37 patients 19 (51%) did not have tumor recurrence, 9 (24%) had superficial recurrence in the bladder that was treated successfully and 9 (24%) had recurrence with advanced disease. A total of 24 patients (65%) had an intact bladder with no evidence of disease after a median of 53 months. There were 6 patients (16%) who died of bladder cancer, 3 of whom died of late recurrence of muscle invasive cancer (41, 44 and 138 months after partial cystectomy). On multivariate analysis higher pathological stage (HR 3.4, p = 0.04) was associated with shorter recurrence-free survival. A history of superficial tumors (p <0.01) and clinical stage (p = 0.01) was associated with advanced recurrence-free survival. The use of adjuvant chemotherapy (HR 0.18, p = 0.03) was associated with prolonged advanced recurrence-free survival, however adjuvant chemotherapy did not impact overall survival.
CONCLUSIONS: Partial cystectomy provides adequate local control of muscle invasive bladder cancer in select patients. Because late recurrence is not uncommon and is potentially life threatening, lifelong followup with cystoscopy is recommended.
John P Stein, Peter Clark, Gus Miranda, Jie Cai, Susan Groshen, Donald G Skinner
Urethral tumor recurrence following cystectomy and urinary diversion: clinical and pathological characteristics in 768 male patients.
J Urol. 2005 Apr;173(4):1163-8. doi: 10.1097/01.ju.0000149679.56884.0f.
Abstract/Text
PURPOSE: We evaluated the incidence and risks of urethral recurrence following radical cystectomy and urinary diversion in men with transitional cell carcinoma of the bladder.
MATERIAL AND METHODS: Clinical and pathological results were evaluated in 768 consecutive male patients undergoing radical cystectomy with intent to cure for bladder cancer with a median followup 13 years, including 397 (51%) who underwent orthotopic urinary diversion with a median followup of 10 years and 371 (49%) who underwent cutaneous urinary diversion with a median followup of 19 years. Demographically and clinically these 2 groups were well matched with the only exception being longer median followup in the cutaneous group (p <0.001). Urethral recurrence was analyzed by univariate and multivariable analysis according to carcinoma in situ, tumor multifocality, pathological characteristics (tumor grade, stage and subgroup), the presence and extent of prostate tumor involvement (superficial vs stromal invasion) and the form of urinary diversion (cutaneous vs orthotopic).
RESULTS: A total of 45 patients (6%) had urethral recurrence at a median of 2 years (range 0.2 to 13.6), including 16 (4%) with an orthotopic and 29 (8%) with a cutaneous form of urinary diversion. Carcinoma in situ and tumor multifocality were not significantly associated with an increased risk of urethral recurrence (p = 0.07 and 0.06, respectively). The presence of any (superficial and/or stromal invasion) prostatic tumor involvement was identified in 129 patients (17%). Prostate tumor involvement was associated with a significantly increased risk of urethral recurrence (p = 0.01). The estimated 5-year chance of urethral recurrence was 5% without any prostate involvement, increasing to 12% and 18% with superficial and invasive prostate involvement, respectively. Patients undergoing orthotopic diversion demonstrated a significantly lower risk of urethral recurrence compared with those undergoing cutaneous urinary diversion (p = 0.02). Patients without any prostate tumor involvement and orthotopic diversion (lowest risk group) demonstrated an estimated 4% year chance of urethral recurrence compared with a 24% chance in those with invasive prostate involvement undergoing cutaneous diversion (highest risk group). On multivariate analysis any prostate involvement (superficial and/or invasive) and urinary diversion form remained independent and significant predictors of urethral recurrence (p = 0.035 and 0.01, respectively).
CONCLUSIONS: At long-term followup urethral tumor recurrence occurs in approximately 7% of men following cystectomy for bladder transitional cell carcinoma. Involvement of the prostate with tumor and the form of urinary diversion were significant and independent risk factors for urethral tumor recurrence. Patients undergoing orthotopic diversion have a lower incidence of urethral recurrence compared with those undergoing cutaneous diversion. Although prostate tumor involvement is a risk factor for urethral recurrence, it should not preclude orthotopic diversion, provided that intraoperative frozen section analysis of the urethral margin is without evidence of tumor.
Nobuo Shinohara, Toru Harabayashi, Shin Suzuki, Kazuhiro Nagao, Haruo Seki, Masashi Murakumo, Kimiyoshi Mitsuhashi, Takayoshi Demura, Satoshi Nagamori, Hideyasu Matsuyama, Katsusuke Naito, Katsuya Nonomura
Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy.
Cancer Chemother Pharmacol. 2006 Sep;58(3):402-7. doi: 10.1007/s00280-005-0175-4. Epub 2006 Jan 17.
Abstract/Text
BACKGROUND AND AIMS: The aim of the present phase II study was to evaluate the efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) in patients with recurrent urothelial cancer who had been treated with cisplatin-based chemotherapy.
PATIENTS/METHODS: Eligible patients were those with histologically confirmed urothelial cancer who had progressed or relapsed after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175 mg/m(2) on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and nedaplatin 70 mg/m(2) on day 1; PIN was given every 28 days.
RESULTS: Among the 32 patients enrolled in the study (median age, 66 years), complete and partial responses were obtained in 5 patients and 19 patients, respectively, with an overall response rate of 75% (95% confidence interval [CI], 59-91%). The median time to progression was 8 months (range, 0-50+ months) and the median survival was 22 months (range, 4-52+ months). The 1- and 2-year overall survival rates were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4 neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3 or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient, for whom the PIN therapy was discontinued. There were no treatment-related deaths.
CONCLUSION: The PIN combination was highly active and tolerable in previously treated patients with urothelial cancer as a second-line treatment.
