|Year : 2012 | Volume
| Issue : 4 | Page : 467-468
Impact of timing of surgery in upper tract urothelial carcinoma
|Date of Web Publication||10-Jan-2013|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Mandal S. Impact of timing of surgery in upper tract urothelial carcinoma. Indian J Urol 2012;28:467-8
Gadzinski AJ, Roberts WW, Faerber GJ, Wolf JS Jr. Long-term outcomes of immediate versus delayed nephroureterectomy for upper tract urothelial carcinoma. J Endourol 2012;26:566-73.
| Summary|| |
Upper tract urothelial carcinoma (UTUC) is a rare disease, accounting for approximately 5% of all renal and urothelial tumors. Radical nephroureterectomy (NUx) with bladder cuff remains the gold-standard treatment but emerging alternatives like ureteroscopic and percutaneous techniques have provided reasonable alternatives to NUx. The initial good results of nephron-sparing approaches in UTUC for imperative indications (like bilateral disease, solitary kidney) led to its successful use in elective (normal contralateral kidney and limited low-grade tumor) situations also. Despite this success, 19-33% of patients managed by nephron-sparing approach experience disease progression necessitating NUx. 
The authors in this retrospective study, report the long-term results of patients who later needed NUx (n = 11) after an initial trial of nephron-sparing management, and compare them with patients who underwent immediate NUx (n = 62). The aim was to elucidate whether delayed NUx adversely affected the final outcome as compared to patients who underwent immediate NUx.
All delayed NUx patients (n = 11) initially underwent ureteroscopic (if failed, percutaneous) complete tumor ablation. UTUC was confirmed with biopsy in most cases and with cytology from saline barbotage in the remaining. After initial successful tumor ablation, patients were counseled regarding continued endoscopic management vs. NUx. Patients who declined endoscopic management or had high-grade disease (not amenable to nephron-sparing) were included in the immediate NUx group. Those who pursued endoscopic management were required to have complete endoscopic tumor resection and agreed to active surveillance. Of the eight patients who were followed at the author's institution, 42 subsequent operations (37 Ureteroscopy, 5 percutaneous) were required. On an average, these eight patients underwent an operation every 3.7 ± 1.0 months while on active surveillance. The reason for delayed NUx was high-volume recurrence (n = 5) and endoscopically unresectable recurrence (n = 5); one patient underwent NUx at an outside institution (unknown reason).
Mean follow-up from initial complete resection in delayed and immediate groups was 61 months and 58 months, respectively. Progression to high-grade disease occurred in three (43%) patients at the time of delayed NUx. For delayed NUx patients, median time to disease recurrence was 4.0 months, and median time to NUx was 10 months. There was no significant difference in overall survival (OS) from date of first complete resection with five-year survivals in the delayed and immediate group of 64% and 59%, respectively. No significant differences were found in the five-year metastasis-free survivals (5 MFS) from initial treatment for delayed and immediate NUx, 77% and 73%, respectively, and in cancer-specific survival (CSS) 91% and 80%, respectively.
Thus the study shows that patients with small, low-grade disease may elect a trial of conservative management knowing that if disease progression necessitates delayed NUx, systemic long-term cancer progression, CSS, 5MFS and OS will not be adversely affected. In cases of resectable low-grade disease, initiating endoscopic monitoring is an alternative to immediate NUx for nephron sparing and only 32% later needed NUx. 
| Comments|| |
These results are critical in determining the relative safety of attempting endoscopic management, especially in light of the reported risks of delaying cystectomy in patients with clinical Stage T2 or higher bladder cancer. Most endoscopically treated UTUC patients are similar to pTa bladder cancer patients, where superficial disease can frequently be treated effectively by transurethral resection, reserving extirpative surgery (cystectomy) for patients with invasive disease progression.
A large study  involving 6078 NUx performed for non-metastatic UTUC reported that overall 90-day perioperative mortality was 4.4%. The mortality rate was 4.4% in patients 70-79 years of age and 8.3% in patients >80 years of age. The most common cause of perioperative death was renal insufficiency (45%). This statistic is critical when elderly patients select radical surgery. Similar large-population statistics for endoscopic procedures were not found in the current literature; however, endoscopic procedures are anecdotally considered safer regarding perioperative mortality.
In this study Gadzinski et al., demonstrate no difference in five-year cancer-specific survival and metastasis-free survival among patients undergoing immediate nephroureterectomy (NUx) and delayed (on an average after 10 months) NUx for small and low-grade upper urinary tract urothelial tumor following endoscopic management. This is in contradiction to a multicentric study of 187 patients which demonstrated that a delay >45 days between diagnosis and resection of the tumor constitutes a risk for disease progression. 
The diagnosis of UTUC is fortuitous or related to the exploration of symptoms which tend to be generally restricted.  Radiological investigations often fail to detect small tumors adding to the diagnostic dilemma.  Thus patients usually present with advanced disease that is not amenable to endoscopic management. Moreover, endoscopic treatment requires advanced instrumentations (like flexible endoscopes, lasers etc.), a dedicated team and high surgical expertise. At present, such treatment can be offered only at select centers of the world thus limiting the wide usage of this technique all over the globe. 
On an average eight patients underwent 42 operations (37 ureteroscopies, 5 percutaneous procedures; 5.2 operations per patient) every 3.7 ± 1.0 months while on active surveillance. In an elderly group of patients repeated procedures under anesthesia may be difficult while repeated ureteroscopies and laser ablation can lead to iatrogenic ureteral strictures as well, further increasing the morbidity. 
Further prospective studies, with a larger number of patients with longer follow-up are required to analyze the results of the present study.
| References|| |
|1.||Gadzinski AJ, Roberts WW, Faerber GJ, Wolf JS Jr. Long-term outcomes of nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma. J Urol 2010;183:2148-53. |
|2.||Jeldres C, Sun M, Isbarn H, Lughezzani G, Budäus L, Alasker A, et al. A population based assessment of perioperative mortality after nephroureterectomy for upper-tract urothelial carcinoma. Urology 2010;75:315-20. |
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|4.||Mandal S, Goel A. Re: Gadzinski AJ, Roberts WW, Faerber GJ, Wolf JS. Long-term Outcomes of Immediate Versus Delayed Nephroureterectomy for Upper Tract Urothelial Carcinoma. J Endourol. 2012 Mar 14. [Epub ahead of print] |
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