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UROSCAN
Year : 2012  |  Volume : 28  |  Issue : 4  |  Page : 464-465
 

Effectiveness of a single post-operative Mitomycin-C on prevention of bladder tumor after nephroureterectomy for primary upper urinary tract urothelial carcinoma


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Date of Web Publication10-Jan-2013

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How to cite this article:
Paul S. Effectiveness of a single post-operative Mitomycin-C on prevention of bladder tumor after nephroureterectomy for primary upper urinary tract urothelial carcinoma. Indian J Urol 2012;28:464-5

How to cite this URL:
Paul S. Effectiveness of a single post-operative Mitomycin-C on prevention of bladder tumor after nephroureterectomy for primary upper urinary tract urothelial carcinoma. Indian J Urol [serial online] 2012 [cited 2019 Oct 14];28:464-5. Available from: http://www.indianjurol.com/text.asp?2012/28/4/464/105796

O'Brien T, Ray E, Singh R, Coker B, Beard R. British Association of Urological Surgeons Section Oncology. Prevention of Bladder Tumours after Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma: A Prospective, Multicentre, Randomised Clinical Trial of a Single Postoperative Intravesical Dose of Mitomycin C (the ODMIT-C Trial). Eur Urol 2011;60:703-10.



   Summary Top


Upper urinary tract urothelial carcinoma (UUTUC) constitutes 10% of renal tumors. Standard management of UUTUC is nephroureterectomy but 40% of these patients develop bladder cancer after surgery [1] due to implantation metastasis. In this multicentric, prospective, randomized study, the authors evaluated the effect of administration of single dose (40 mg) of intravesical Mitomycin-C (MMC) in the early postoperative period, before catheter removal (to minimize the risk of extravasation) after nephroureterectomy for UUTUC to prevent seeding of transitional cancer cells and thereby reduce bladder carcinoma in the first year postsurgery.

Suspicion of UUTUC was based on imaging, urine cytology, or appearances at ureterorenoscopy and a histologic proof of UUTUC prior to nephroureterectomy was not required. The primary endpoint was the incidence of bladder carcinoma in the first 12 months following nephroureterectomy. Patients (n=284) with no prior or concurrent history of bladder carcinoma were enrolled in the study. After randomization, 105 of 144 patients allocated to the MMC group received MMC and 115 of 140 patients allocated to the non-MMC group received standard postoperative care. Follow-up cystoscopy was done at 3, 6, and 12 months postsurgery and recurrence was judged on visual appearance (histologic proof was not required). Recurrence was observed in 17 out of 105 (16%) MMC-treated arm and 31 of 115 (27%) of the standard treatment arm (P=0.03). Recurrence was only seen in 1 of 18 patients (6%) who had a well-differentiated tumor but in 31 of 122 patients (25%) with moderately differentiated and 20 of 92 patients (22%) with poorly differentiated tumors. There were no serious adverse events reported as a result of MMC treatment.

Thus, this largest randomized trial ever performed on the management of patients with UUTUC concluded that single dose of intravesical MMC can reduce the risk of developing a bladder carcinoma in the subsequent year by almost 40%, with little risk of an adverse event.


   Comments Top


The pathogenesis of bladder carcinoma following previous UUTUC is controversial. It could result either due to the field effect, or due to implantation metastases resulting from seeding. Molecular and clinical evidence suggests that seeding is a possible factor. The molecular evidence suggests that UUTUC and bladder carcinoma are often monoclonal. [2] Multifocal bladder tumors could be monoclonal and therefore were likely to be implantation metastases. [3] The clinical evidence supporting implantation metastasis of UUTUC is threefold: first, around 70% of cases that develop following nephroureterectomy do so in the first year following surgery; [3] second, the incidence of bladder carcinoma following a diagnosis of UUTUC is about 35%, whereas the incidence of UUTUC following a bladder tumor is around 5%; [3] third, single dose of intravesical chemotherapy following transurethral resection of a bladder tumor reduces recurrence from around 40% to 26%. [4]

The intravesical administration of MMC [4] possibly reduces successful seeding of cells shed from the UUTUC. The milieu in the bladder at the time of nephroureterectomy is conducive to tumor growth for three reasons: (1) manipulation of the tumor could lead to tumor cells' shedding; (2) various angiogenic factors are supposed to release from the bladder wound into the bladder; and (3) the patient is immunocompromised to a degree by surgery. MMC in this study could not have prevented implantation, but could possibly have prevented cells that did implant themselves from establishing a significant new tumor.

There were some demerits related to the study like a histological proof for recurrence was not considered. Moreover, no attempts were made to match potential risk factors particularly multifocality and grade of tumor.

MMC affects only the mucosal surface of the bladder and has minimal side effects. [5] It has been suggested [5] that intravesical MMC can be given 2 days prior to nephroureterectomy. This dose may prevent implantation of tumor cells at the time of nephroureterectomy and thus may partially overcome the problem associated with delayed instillation. As the effect of MMC is confined to the mucosa, there would be no risk of delayed wound healing of the bladder.

Importantly, the question remains as to what will be the impact of this trial, which provides level 1 evidence to support the use of intravesical MMC after nephroureterectomy, on clinical practice? The answer would come from upcoming studies from different centers with larger study population and where histopathological conformation is done both preoperatively and postoperatively. Until then, due to scarcity of level 1 evidence in urological literature, the author's recommendation seems acceptable.

 
   References Top

1.Wu WJ, Ke HL, Yang YH, Li CC, Chou YH, Huang CH. Should patientswith primary upper urinary tract cancer receive prophylactic intravesical chemotherapy after nephroureterectomy? J Urol 2010;183:56-61.  Back to cited text no. 1
[PUBMED]    
2.Habuchi T, Takahashi R, Yamada H, Kakehi Y, Sugiyama T, Yoshida O. Metachronous multifocal development of urothelial cancers byintraluminal seeding. Lancet 1993;342:1087-8.  Back to cited text no. 2
[PUBMED]    
3.Krogh J, Kvist E, Rye B. Transitional cell carcinoma of the upperurinary tract: Prognostic variables and post-operative recurrences. Br J Urol 1991;67:32-6.  Back to cited text no. 3
[PUBMED]    
4.O'Brien T, Ray E, Singh R, Coker B, Beard R. British association of urological surgeons section oncology. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: A prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol 2011;60:703-10.  Back to cited text no. 4
    
5.Goel A, Paul S. Re: O'Brien T, Ray E, Singh R, Coker B, Beard R. British association of urological surgeons section oncology. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: A prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol 2012;61:e14.  Back to cited text no. 5
    




 

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