T1 Bladder Cancer

Reviewing the Literature

RIU0368_12-12.qxd 12/12/07 8:29 PM Page 239 REVIEWING THE LITERATURE News and Views from the Literature T1 Bladder Cancer Selecting Patients for Immediate Cystectomy Reviewed by Shahrokh F. Shariat, MD Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX [Rev Urol. 2007;9(4):239-241] © 2007 MedReviews, LLC to accurately identify life-threatening, high-grade T1 tumors. Multiple tumors, larger size (more than 3 cm), carcinoma in situ (CIS), and tumor at first follow-up cystoscopy after treatment are associated with greater risk of disease progression and reduced survival. Other prognostic factors under investigation are lymphovascular invasion, depth of lamina propria invasion, and tumor marker expression.6-8 Can Restaging Transurethral Resection of T1 Bladder Cancer Select Patients for Immediate Cystectomy? Herr HW, Donat SM, Dalbagni G. anagement of high-grade urothelial carcinoma of the bladder involving the lamina propria (stage T1) but not penetrating into the muscularis propria represents a challenge for both physician and patient. There is no level I evidence to direct us. Transurethral resection (TUR) has long been recognized as an inadequate complete treatment, with recurrence rates approaching 80% and the risk of progression to muscle invasion approaching 60%.1,2 Adjuvant intravesical therapy with Bacille Calmette-Guérin (BCG) or chemotherapeutic agents, such as mitomycin C, may decrease the overall recurrence rate by approximately 30% compared with TUR alone,3,4 but tumor progression still occurs in 15% to 40% of patients within the first 5 years, and these patients are at risk of dying from urothelial cancer.4,5 It remains difficult M J Urol. 2007;177:75-79 This article by Herr and colleagues shows that restaging TUR can identify patients at high risk for tumor progression, and, thus, can be used to stratify which patients should be offered early cystectomy. A cohort of 352 patients with T1 bladder cancer underwent a second or restaging TUR after a 2- to 4-week interval. All patients received induction BCG therapy, but none received maintenance therapy. Overall 203 (58%) had residual tumor on restaging TUR, from which 92 (26%) had T1 cancer. During the first 5 years, 66% of patients experienced disease recurrence, and 35% experienced progression to muscleinvasive disease. Five-year progression rates based on findings on restaging TUR increased from 8% for patients VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 239 RIU0368_12-12.qxd 12/12/07 8:29 PM Page 240 T1 Bladder Cancer continued with no residual tumor to 16% for those with residual TaG3 tumor, to 37% for those with CIS, and reached 82% for those with residual T1 tumor. In other words, 75 of the 92 patients with residual T1 cancer on restaging TUR (82%) experienced disease progression to muscle invasion within the first 5 years (median follow-up 7.5 years [range: 1-14]). In a multivariate analysis of risk factors, restaging TUR pathology was the most important single determinant associated with tumor progression (HR 6.7; P
.001) followed by the presence of complete response to BCG at first cystoscopy performed 3 to 6 months after TUR (HR 2.7; P
.001), presence of multiple tumors (HR 3.3; P  .04), and high-grade disease (HR 3.1; P  .05). These authors found that the majority of patients with high-grade T1 who had residual T1 cancer on restaging TUR had lifethreatening muscle-invasive cancer within 12 to 17 months despite bladder-sparing methods. There was a clear difference in progression rates between T1 low-grade and high-grade categories. The authors concluded that patients who have high-grade T1 disease on restaging TUR at 2-4 weeks after primary resection are at high risk for early tumor progression and therefore should be considered for/offered early cystectomy. This study has limitations. First and foremost, it is a retrospective study. Second, some of the patients may not have undergone complete TUR in the first instance. Third, none of the patients received maintenance BCG, an approach that has been demonstrated to decrease progression rates relative to induction BCG alone. Fourth, none of the patients had immediate postoperative chemotherapy to reduce post-resection seeding, a technique that has been confirmed in multiple, randomized, clinical trials and a meta-analysis to reduce tumor recurrence significantly.9 However, I believe that intravesical therapy targets “floating” cells and abnormal bladder mucosa not included in the resection sites, whereas TUR is directed at eradicating the invasive component of the disease. Therefore, incomplete resection and tumor implantation can be avoided by including biopsy adjacent to the tumor, extended resection of the base and margins, and immediate postoperative chemotherapy. The evidence of a high incidence of residual or recurrent bladder tumor (64%-78%) following resection by competent, experienced urologists is consistent and convincing, and supports the routine use of repeat TUR.10,11 Therefore one should perform routinely a second TUR 2-6 weeks after the first to identify patients at high risk of early tumor recurrence and progression. This is preferable to waiting for progression to muscle-invasive disease, as high-risk patients who would benefit from immediate cystectomy can be identified in time. Herr and Donat’s earli- 240 VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY er work suggested that these patients might be better served by immediate cystectomy rather than BCG therapy. Understaging is among the limitations of effective surveillance and appropriate treatment. The accuracy of staging is poor, with only 50% of clinical T1 patients accurately staged.12-14 Several reports have shown that approximately 10%-15% of patients treated with radical cystectomy for high-grade T1 disease have lymph node metastases.15-18 The rate of nodal involvement increases proportionally to the number of TURs before cystectomy.15 Radical cystectomy is a highly effective treatment for pathologically organ-confined bladder cancers, with 5year recurrence-free survival rates ranging from 80% to 88%.18,19 Patients with clinical stage T1 cancers who undergo early rather than delayed cystectomy have substantially better 5-year recurrence-free survival rates (90% vs 62%).20 Moreover, patients who experience progression to muscle-invasive disease have a significantly worse survival compared with those who present with de novo clinical T2 disease (3-year bladder-cancer-specific survival: 37% vs 67%).21 Moreover, patients with high risk non-muscle-invasive bladder tumors who underwent earlier rather than delayed cystectomy for tumor relapse after initial treatment with TUR and BCG therapy were shown to have a better survival rate (92% for patients who underwent cystectomy less than 2 years after initial BCG therapy vs 56% for patients treated after 2 years).22 Taken together, these data imply that radical cystectomy should be performed sooner rather than later for recurrent highgrade T1 cancers. Therefore, with current limitations of staging modalities, waiting for muscle-invasion before performing cystectomy may be too late for optimal quality of life and oncologic outcomes in patients with highgrade T1 bladder cancer. Patients must be counseled and educated early regarding the need for cystectomy so that it does not come as a surprise and lead to unwanted delay. Despite technical advances that may minimize the impact of bladder removal on health-related quality of life, such as nerve-sparing and prostate-sparing techniques, and the application of orthotopic urinary diversion to a broad array of patients in certain centers, the functionality of diversion typically falls short of that of the native bladder. Furthermore, the perioperative consequences of radical cystectomy are not trivial, with morbidity and mortality rates approaching 30% and 3%, respectively.20 Given the potential benefits and trade-offs associated with cystectomy for clinical stage T1 bladder cancer, in what contexts is extirpative treatment appropriate? The ideal candidate for conservative treatment of T1 bladder cancer is a patient with a solitary or at least completely resectable tumor, a negative upper-tract evaluation, and RIU0368_12-12.qxd 12/12/07 8:29 PM Page 241 Incontinence no evidence of invasive disease in the prostatic urethra. Patients with T1 tumors should be considered for cystectomy if they have: 1. multifocal or extensive tumors that cannot be completely and reliably resected, either during the first resection or soon thereafter 2. deep penetration of the lamina propria approaching muscularis propria 3. involvement of the prostatic mucosa or ducts 4. recurrent T1 within 3 months after intravesical therapy 5. residual T1 disease on repeat TUR 6. concurrent CIS or onset while receiving therapy 7. micropapillary variant 8. extensive invasion of the lymphatic space 9. poor patient compliance The presence of 1 or more of these risk factors should prompt the clinician to consider the pitfalls of proceeding with conservative treatment compared with the trade-offs of radical cystectomy. Whereas a single risk factor may not be sufficient to warrant early cystectomy, the aggregate risk of multiple factors supports the need for immediate cystectomy. 14. 15. 16. 17. 18. 19. 20. 21. 22. tumors: a combined analysis of 5 European Organization for Research and Treatment of Cancer Trials. J Urol. 2000;164:1533-1537. Shariat SF, Palapattu GS, Karakiewicz PI, et al. Discrepancy between clinical and pathologic stage: impact on prognosis after radical cystectomy. Eur Urol. 2007;51:137-149. Wiesner C, Pfitzenmaier J, Faldum A, et al. Lymph node metastases in nonmuscle invasive bladder cancer are correlated with the number of transurethral resections and tumour upstaging at radical cystectomy. BJU Int. 2005;95: 301-305. Bianco FJ Jr, Justa D, Grignon DJ, et al. Management of clinical T1 bladder transitional cell carcinoma by radical cystectomy. Urol Oncol. 2004;22: 290-294. Nieder AM, Simon MA, Kim SS, et al. Radical cystectomy after bacillus Calmette-Guérin for high-risk Ta, T1, and carcinoma in situ: defining the risk of initial bladder preservation. Urology. 2006;67:737-741. Shariat SF, Karakiewicz PI, Palapattu GS, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the bladder cancer research consortium. J Urol. 2006;176:2414-2422. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19:666-675. Stockle M, Alken P, Engelmann U, et al. Radical cystectomy—often too late? Eur Urol. 1987;13:361-367. Schrier BP, Hollander MP, van Rhijn BW, et al. Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy. Eur Urol. 2004;45:292-296. Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol. 2001;166:1296-1299. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Heney NM. Natural history of superficial bladder cancer. Prognostic features and long-term disease course. Urol Clin North Am. 1992;19:429-433. Heney NM, Ahmed S, Flanagan MJ, et al. Superficial bladder cancer: progression and recurrence. J Urol. 1983;130:1083-1086. Shelley MD, Court JB, Kynaston H, et al. Intravesical bacillus Calmette-Guérin versus mitomycin C for Ta and T1 bladder cancer. Cochrane Database Syst Rev: CD003231. 2003. Huncharek M, Kupelnick B. The influence of intravesical therapy on progression of superficial transitional cell carcinoma of the bladder: a metaanalytic comparison of chemotherapy versus bacilli Calmette-Guérin immunotherapy. Am J Clin Oncol. 2004;27:522-528. Cookson MS, Herr HW, Zhang ZF, et al. The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol. 1997;158:62-67. Shariat SF, Weizer AZ, Green A, et al. Prognostic value of P53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder. Urology. 2000;56:735-740. Shariat SF, Kim JH, Ayala GE, et al. Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder. J Urol. 2003;169:938-942. Shariat SF, Ashfaq R, Sagalowsky AI, Lotan Y. Predictive value of cell cycle biomarkers in nonmuscle invasive bladder transitional cell carcinoma. J Urol. 2007;177:481-487. Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol. 2004;171:2186-2190. Herr HW, Donat SM. A re-staging transurethral resection predicts early progression of superficial bladder cancer. BJU Int. 2006;97:1194-1198. Herr HW. Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guérin therapy. J Urol. 2005;174:2134-2137. Chang BS, Kim HL, Yang XJ, Steinberg GD. Correlation between biopsy and radical cystectomy in assessing grade and depth of invasion in bladder urothelial carcinoma. Urology. 2001;57:1063-1066. Van Der Meijden A, Sylvester R, Collette L, et al. The role and impact of pathology review on stage and grade assessment of stages Ta and T1 bladder Incontinence Curing Stress Urinary Incontinence, or Shades of Dryness Reviewed by Frank Costa, MD, Michael Chancellor, MD Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA. [Rev Urol. 2007;9(4):241-242] © 2007 MedReviews, LLC istorically the gold standard in treatment of stress urinary incontinence (SUI) in urologists' hands is the pubovaginal sling, whereas gynecologists have often preferred the Burch and MMK procedure. The ageadjusted rate of inpatient surgical procedures for SUI in women in the United States increased from 0.32 per 1000 women in 1979 to 0.60 per 1000 women in 1997. Given the aging of the US population, the total number of procedures for treatment of SUI is expected to continue to rise. Yet there are few data from randomized trials to inform surgical decision making. We would like to review an important recent paper and companion editorial on this topic in the New England Journal of Medicine. H VOL. 9 NO. 4 2007 REVIEWS IN UROLOGY 241