european urology 50 (2006) 1129 1138 available at www.sciencedirect.com journal homepage: www.europeanurology.com Editorial 50th Anniversary Radical Cystectomy Often Too Late? Yes, But... Urs E. Studer * University Hospital of Bern, Department of Urology, Bern, Switzerland The editors of European Urology elected to reprint this manuscript, which was initially published almost 20 yr ago and continues to contain important messages. Not only was the Mainz group one of the initiators advocating radical cystectomy as the optimal treatment for invasive bladder cancer, but they also made the following important points that are still true to this day. In the hands of experienced surgeons, the mortality rate of radical cystectomy is low. In addition, the evolution of urinary diversion has provided patients a more normal lifestyle and improved self-image after bladder removal. The presence or absence of tumour invasion across the basal membrane is a significant prognostic factor. As long as the basal membrane is intact, even multifocal or recurrent noninvasive tumours have albeit a high recurrence, but a low progression rate [1]. If, however, the bladder cancer penetrates the basal membrane, then it has the potential to infiltrate and disseminate. Indeed, the prognosis of patients with T1 grade 3 cancer that invades the muscularis mucosa is just as poor as a T2a/ T2b cancer that deeply invades the detrusor muscle [2]. Consequently, the conclusion at a recent bladder cancer consensus meeting was to abandon the expression superficial bladder cancer, for both Ta G1/G2 papillary tumours and T1G3 invasive bladder cancers [3]. These two heterogenous groups not only have a different prognosis but also require different treatment algorithms [3]. The authors pointed to the relevance of lymphovascular invasion. It is the reason that some patients die of progressive disease even when no cancer is found in the cystectomy specimen (pt0). Death results from micrometastases that were present at the time of cystectomy. Perhaps the most provocative finding of the manuscript is that the group of patients who had cystectomy immediately after initial diagnosis of bladder cancer (group A) fared significantly better than the group who underwent cystectomy for recurrent disease (group B) despite apparently similar pt stages. Approximately 70% of the cystectomy specimens in both groups had organ-confined disease, that is, pt1/pt2 according to the UICC 1978 classification. The impressive difference observed in the overall survival for the two groups with apparently similar tumour stages but with either immediate or deferred cystectomy motivated the authors to recommend early cystectomy for all patients with superficially invasive bladder cancer (pt1). Even though the above finding has repeatedly been confirmed by others [4], one must be aware that the two groups with either immediate or deferred cystectomy are not comparable. The patients who underwent a deferred cystectomy were initially part of a larger group of patients with superficially invasive bladder cancer (pt1) who were managed conservatively with transurethral resection (TUR) and intravesical immunotherapy or chemotherapy. Obviously, only patients in whom the bladder-sparing policy failed were referred for * Tel. +41 31 6323641; Fax: +41 31 6322191. E-mail address: urs.studer@insel.ch. 0302-2838/$ see back matter # 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2006.07.056
1130 european urology 50 (2006) 1129 1138 cystectomyandallocatedtotheabovegroupb.asa result, group B represents only the subset of patients in whom conservative therapy failed and is known to have a particularly poor prognosis [5] and excludes all those successfully treated conservatively. Therefore, when determining the outcome of conservative management for organconfined bladder cancer it is imperative to not only evaluate the subgroup that failed but also to consider the subgroup of patients (50 70%) in whom disease did not progress. Indeed, several series report a 60 80% 5-yr progression-free survival rate for T1G3 bladder cancer patients treated with TUR and intravesical immunotherapy/chemotherapy [6,7] provided that cystectomy was performed when early or multiple recurrences were diagnosed. With immediate radical cystectomy for T1G3/T2 bladder cancer the 5-yr progression-free survival is also reported to be 65 85% [1,8,9]. Thus, the outcome of the two treatment approaches does not seem to differ that much. The answer to the question of immediate versus deferred cystectomy for superficial invasive bladder cancer is not quite so evident. Perhaps this is why Dr Stoeckle added the question mark to his title. Today, radical cystectomy is considered the safest way to treat invasive bladder cancer, even if it is organ-confined. However, radical cystectomy is still an aggressive form of treatment and it is our responsibility to use it judiciously and appropriately. Therefore, the following recommendations can made to the practicing urologist: For small (<1.5 cm) solitary organ-confined invasive bladder cancer (stage T1, rarely T2a) a radical TUR can be offered as a therapeutic strategy, provided random biopsies are negative and no residual tumour is found in a vigorous repeated resection of the primary tumor site [10]. However, with this treatment strategy, there still is a small risk of persistent perivesical lymphatic tumour spread. In some of these cases cystectomy combined with a meticulous pelvic lymph node dissection may be curative. Radical cystectomy offers the best chance of cure for patients with recurrent invasive T1G3 disease after failed conservative management who were initially diagnosed with multifocal T1G3 bladder cancer, especially those with concomitant carcinoma in situ, as well as for patients with extensive invasive cancer. Of concern is the poor prognosis for patients with non organ-confined disease, that is, stage pt3a/b. Although the chance of cure has improved since the early reports of 20% and 40% to current reports of 60%, the death toll is still too high [1,7,8]. Itis often argued that this disease, if diagnosed at an earlier stage, would result in improved overall survival. This is certainly true, but it must be noted that 85 90% of patients with pt3 disease are diagnosed with this advanced tumour stage when they become symptomatic for the first time and is not the result of an inadequately prolonged bladder preservation treatment strategy for initially superficial or organ-confined bladder cancer. So although an institution may elect to perform more cystectomies for noninvasive bladder tumours or superficially invasive bladder cancers, and thus improve the overall cystectomy results of the institution, it will not decrease the prevalence of patients with pt3/pt4 bladder cancer nor increase their overall survival rate. For early detection of asymptomatic invasive bladder cancer, programs to screen for microhaematuria would be more helpful [11]. References [1] Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49: 466 75. [2] Stein JP, Lieskovsky G, Skinner DG, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1054 patients. J Clin Oncol 2001; 19:666 75. [3] Soloway M, Carmack A, Khoury S, editors. Bladder tumors. Health Publications; 2006. pp. 141 2. [4] Volkmer B, Hautmann R, Gschwend J. Early versus late cystectomy for T1G3 transitional cell carcinoma (TCC) of the bladder. Eur Urol Suppl 2006;5:24 (abstract no. 5). [5] Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol 2001;166:1296 9. [6] Serretta V, Pavone C, Ingargiola GB, et al. TUR and adjuvant intravesical chemotherapy in T1G3 bladder tumors: recurrence, progression and survival in 137 selected patients followed up to 20 years. Eur Urol 2004;45:730 5. [7] Pansadoro V, Emiliozzi P, Sternberg CN, et al. Long-term follow-up of G3 T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Guérin: 18-year experience. Urology 2002;59:227 31. [8] Madersbacher S, Hochreiter W, Studer UE, et al. Radical cystectomy for bladder cancer today a homogeneous series without neoadjuvant therapy. J Clin Oncol 2003; 21:690 6.
european urology 50 (2006) 1129 1138 1131 [9] Hautmann RE, Gschwend JE, Volkmer BG, et al. Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 2006;176:486 92. [10] Herr HW. Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. J Clin Oncol 2001;19:89 93. [11] Messing EM, Teot L, Bostwick DG, et al. Performance of urine test in patients monitored for recurrence of bladder cancer: a multicenter study in the United States. J Urol 2005;174:1238 41.
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