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Ureteroscopic Treatment and Surveillance of Upper Urinary Tract Transitional Cell Carcinoma
0022-5347/97/1575-1560$03.00/0
Vol. 157, 1560-1565,May 1997 Printed in U.SA,
THEJOURNAL OF UROLOGY Copyright 0 1997 by AMERICAYUROLOCICAL ASSCCLKT~ON. Isc
Original Articles URETEROSCOPIC TREATMENT AND SURVEILLANCE OF UPPER URINARY TFUCT TRANSITIONAL CELL CARCINOMA FRANCIS X. KEELEY, J R . , MARLUCE BIBBO
AND
DEMETRIUS H. BAGLEY
From the Departments of Urology, Radiology and Cytology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
ABSTRACT
Purpose: We determined the efficacy of ureteroscopic t r e a t m e n t of upper u r i n a r y t r a c t t r a n s itional cell carcinoma. Materials a n d Methods: Of 92 patients diagnosed with upper u r i n a r y t r a c t transitional cell carcinoma at o u r institution from 1985 t o 1995, 38 (41 kidneys) u n d e r w e n t ureteroscopic treatment and followup. Semirigid and flexible ureteroscopes were used t o examine the collecting system. T u m o r s were biopsied, and t r e a t e d w i t h fulguration, the neodymium:YAG laser and/or the ho1mium:YAG laser. Patients were t r e a t e d every 6 t o 12 weeks until tumor-free a n d then followed o n a strict endoscopic protocol. Results: Mean and m e d i a n followup w a s 35.1 a n d 26 months, respectively (range 3 t o 116). Grading of ureteroscopic biopsies w a s possible in 40 of 41 cases. Initial grading of tumors w a s low (grade 1 o r 1 t o 2) in 21 kidneys, grade 2 in 14 and grade 3 in 5. Of 41 ludneys 28 (68%)were documented as tumor-free ureteroscopically at some time following t r e a t m e n t , including 8 (29%) w i t h subsequent recurrences that were treated endoscopically a n d 24 (86%)with n o evidence of disease at the most recent followup. No p a t i e n t to d a t e has had progression of disease during endoscopic followup. High t u m o r grade, size a n d multifocality w e r e significantly associated w i t h t u m o r persistence a n d recurrence. Location in the kidney versus ureter w a s n o t a significant prognostic factor. Of the r e c u r r e n t t u m o r s 75% were n o t identified radiographically but were only discovered endoscopically. Two of 8 kidneys removed after endoscopic treatment had n o t u m o r stage (pTO). Conclusions: Endoscopic treatment of u p p e r u r i n a r y t r a c t transitional cell carcinoma is a reasonable method t o treat carefully select patients based on strict indications. Complete endoscopic followup at regular intervals is essential to rule out recurrences. KEYWORDS:carcinoma, transitional cell; kidney neoplasms; ureteral neoplasms; laser surgery Transitional cell carcinoma of the upper urinary tract is relatively uncommon, accounting for 2 to 5% of urothelial tumors. The standard treatment consisted of nephroureterectomy with a cuff of bladder, which was adopted due to the unacceptably high recurrence rate associated with more conservative procedures.' Nephron sparing surgery has been attempted in special circumstances, such as tumors in a solitary kidney or in patients with bilateral disease, but recurrence rates have been high. In contrast, low grade, low stage distal ureteral tumors can be treated with distal ureterectomy alone with a high cure rate.2 Endoscopic treatment of neoplasms of the upper urinary tract has become possible with the development of improved instrumentation. A combination of accurate endoscopic diagnosis with techniques for tissue ablation makes endoscopic therapy possible. Ureteroscopic techniques now allow access to the entire collecting system without prior dilation of the ureter.".4 Improved biopsy and cytopathological techniques have improved ureteroscopic diagnosis of upper urinary tract Accepted for publication November 8, 1996. Editor's Note: This article is the first of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1910 and 1911.
endoluminal lesions.5.6 The development of small diameter electrosurgical devices and lasers has allowed for precise ablation of tumors.7 Several investigators reported results of endoscopic percutaneous*-ll or uretero~copic,12-~4 treatment of upper urinary tract tumors. We present our experience with 41 kidneys in 38 patients with transitional cell carcinoma of the upper urinary tract treated with endoscopic resection and regular ureteroscopic followup. We also report the pathological findings of open surgical specimens from 8 patients initially treated endoscopically. PATIENTS AND METHODS
Of 92 patients diagnosed ureteroscopically with transitional cell carcinoma of the upper urinary tract from 1985 to 1995, 46 underwent purely diagnostic ureteroscopy followed by open extirpation, while 46 underwent some form of endoscopic treatment. Of the latter patients 8 underwent open surgery following endoscopic therapy, leaving 14 women and 24 men (mean age 70.9 years, range 45 t o 87) who were treated endoscopically and followed on our surveillance protocol. At least 1 followup ureteroscopic examination was done in all 38 patients. The right and left collecting systems were
1560
1561
URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
involved in 26 and 15 cases, respectively (3 had bilateral involvement). Patients with positive cytology results from the upper urinary tract without evidence of gross exophytic neoplasm were not included in this study. Patients presented with a variety of signs and symptoms, including gross hematuria (16),microscopic hematuria (4), filling defects found during followup of bladder cancer (8), flank pain secondary to obstruction (3)and cystoscopically detected tumor fronds in a ureteral orifice (6). All patients had a history of cigarette smoking. Evaluation included cystoscopy, retrograde ureteropyelography, semirigid and flexible ureteroscopy, and biopsy of any visible tumor. Tumor in the lower pole calix of 1patient was an incidental finding during antegrade (percutaneous) endopyelotomy. All other cases were diagnosed ureteroscopically. Specimens were obtained by aspiration, saline wash biopsy with cup forceps, flat wire basket or graspers; postbiopsy aspiration, and post-laser aspiration. Multiple specimens were obtained during each p r o c e d ~ r e . ~ ~ . ~ ~ Once transitional cell carcinoma was diagnosed in tissue patients were counseled on the risks and benefits of open versus endoscopic treatment. It was emphasized consistently that open surgery was the standard treatment for upper urinary tract transitional cell carcinoma. Endoscopy with followup was chosen by 38 patients for a variety of indications, including a solitary kidney (7)or bilateral disease (8), palliation (21, renal insufficiency (2), high medical risk for open surgery (8),preference (4) and small, low grade tumors
(7). Ureteroscopic treatment consisted of removal or ablation of tissue using electrosurgical devices, mechanical techniques and lasers. Since 1994 we have used a combination of needymium:YAG and ho1mium:YAG lasers for coagulation and ablation of tumors as described previously.'*l6 Select patients with multifocal, large or incompletely treated tumors received 40 mg. mitomycin C in 3 divided doses via a ureteral catheter in the immediate postoperative period. Some patients with significant bladder and upper urinary tract disease were treated with a standard course of intravesical bacillus Calmette-Guerin (BCG) with an indwelling ureteral stent. Patients were examined with cystoscopy and ureteroscopy 3 months after initial treatment. Persistent or recurrent tumor was treated and the patients were examined again 3 months later. When found endoscopically at the same site it was impossible to determine if the tumor was, in fact, persistent or recurrent. A lesion at another site could be considered a recurrence or new tumor. The decision for continued endoscopic therapy or nephmureteredomy was based on the size, location and grade of the lesion, as well as patient desire.
If there was no evidence of tumor patients were followed on the surveillance protocol. Patients with large tumors requiring debulking were treated a t more frequent intervals (every 6 to 12 weeks) until tumor-free or a decision was made for other treatment. Followup consisted of cystoscopy and cytology at 3-month intervals, retrograde ureteropyelography and ureteroscopy at 6-month intervals, and imaging of the contralateral kidney at 12-month intervals. Several patients with severe medical problems were followed on a less rigorous schedule. Of the patients 11 were followed by a local urologist after a mean of 45 months of surveillance at our institution. Each patient was recently contacted and the records were reviewed. Recurrence was defined as grossly visible tumor on ureteroscopy andor a positive cytology study. Statistical analysis was performed with Fisher's exact test. RESULTS
During a 10-year period 49 renal units in 46 patients were treated endoscopically: 41 renal units in 38 patients who underwent only endoscopic treatment were followed endoscopically for a t least 3 months (mean 35.1, median 26, range 3 to 116)and 8 patients underwent nephroureterectomy after endoscopic treatment. Tumors were treated on a t least 90 separate occasions, with more than 200 ureteroscopic procedures being performed in these patients. Treatment consisted of fulguration only in 19 cases, ne0dymium:YAG laser only in 23, h0lmium:YAG laser only in 22 and combinations of each in 26. Of the renal units 28 (68%)were rendered tumor-free after an average of 1.57 ureteroscopic treatments (median 1,range 1to 6), including 8 (29%) that had recurrences.At the most recent followup 24 of the 28 tumor-free renal units (86%)had no evidence of disease, including 9 of 10 (90%)cases followed for at least 5 years. Overall, 24 of 41 renal units (59%) had no evidence of disease. No patient to date has suffered local or metastatic progression of disease during followup and none has had a bulky recurrence necessitating extirpation. Trrmor grade. Every patient had transitional cell carcinoma documented by positive cytology results. Grading of ureteroscopic biopsies by routine histopathological analysis, cell block technique or Cytospin tests was documented in 40 of 41 cases (table 1).One patient without disease grade had a 1 cm. papillary tumor in an upper pole calix and was followed for 82 months without recurrence. Low grade tumors (grade 1 or 1 and 2) were found in 21 renal units in 19 patienta (tumor size 0.5 to 3 cm.,mean 1.57). Of21 renal units 16 (76%)were rendered tumor-& at some time, including 4 (25%) that had recurrences with a mean followup of 40.3 months. At the most recent followup 15
TABLE1. Comparison of patients by tumor gmde,tumor size and indication versus disease-free and recurrence mtes No. Kidneys
No. TumorFree (%)
No Evidence of Disease
No. Reeurrenees
No. Pta.
%Au
(%)
(%)
Pts.
Mean Followup (mos.)
Grade:
LOW
21 14 5 41t
2 3
16 (76) 9 (64)
28 (68) Totals Tumor size (cm.): Less than 1.5 20 (91) 22 More than 1.5 19 7 (36) Indication: Elective 11 10 (91) Relative 8 7 (87) Absolute 20 10 (50) 2 160) Palliative * Followup was too short to amwas recurrence rate. f One patient had a tumor without a grade. $ Only 6 patienta had adequate followup for conaideration of recurrence. ~
4 (25.7) 4 (44.4)
-* -
15 (94) 6 (66) 2 (100) 24 (86)
5 (25) 3 (50)$
20 (91) 4 (21)
8
2 2 4
(29)
(20) (29)
(40)
-*
9 6 8 1
71 43
40 -
40.3 27.6 21
59
(82) (76)
60
(40) (60)
34
25
-
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URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
of 16 tumor-free renal units (94%)and 15 of 21 overall (71%) contraindication to definitive extirpation and palliativehad no evidence of disease. Grade 2 tumors occurred in 14 large, bleeding tumors in patients who would not tolerate renal units in 14 patients (tumor size 0.5 to 3 cm., mean open surgery. As expected, patients treated for elective or 1.88).Of 14 renal units 9 (64%)were rendered tumor-free a t relative indications had a high 1ikeWlood of becoming tumorsome time, including 4 (44%)that had recurrences with a free as well as low recurrence rates, while those with absomean followup of 27.6 months. At the most recent followup 6 lute or palliative indications fared worse (table 1). Incidence of bladder tumors. O v e r d 20 patients (53%)had of 9 tumor-free renal units (66%)and 6 of 14 overall (43%) had no evidence of disease. Grade 3 tumors were noted in 5 a history of transitional cell carcinoma of the bladder at renal units in 4 patients (tumor size 0.5to 3 cm., mean 2.1). diagnosis. Bladder tumors occurred during followup in 15 Two renal units were rendered disease-free. Followup was patients (40%),including 9 of 20 (45%)with and 6 of 18 (33%) too short to assess recurrence rates. Two kidneys had no without a history of transitional cell carcinoma of the bladder. Of the patients with such a history 7 were treated with evidence of disease a t the most recent followup. Tumor size. The size of the tumor correlated strongly with intravesical BCG during followup and 1 had invasive transtreatment success (table 1). Only 7 of 19 renal units (36%) itional cell carcinoma of the bladder. Accuracy of retrograde ureteropyehgruphy. Overall there with tumors larger than 1.5 ern. were ever rendered tumorfree, and 3 of 6 tumor-free renal units (50%) with adequate were 16 recurrences in 8 patients who at some point had been followup subsequently had recurrence. At the most recent fol- tumor-free (table 2). Only 4 recurrences were noted on retlowup (mean 22 months) 4 of 7 tumor-free renal units (57%) rograde ureteropyelography, so that the sensitivity in diagand only 4 of 19 collecting systems (21%) had no evidence of nosing recurrences was only 25%. Additional abnormalities disease. In contrast, 20 of 22 renal units (91%) with initial not related to recurrence were found on 4 retrograde studies, tumors no larger than 1.5 cm.have ever been rendered tumor- while 8 were read as normal. Pathological findings after open surgery. Of the patients 8 free and only 5 (25%) tumor-free kidneys had recurrences. At the most recent followup (mean 45 months) all 20 tumor-free underwent open extirpation after ureteroscopic treatment renal units (100%) and 20 of 22 collectingsystems overall (91%) due to high volume disease (2),persistent disease (4) or patient choice (2).The ureteroscopie biopsy, final pathologihad no evidence of disease. Multifocality. A total of 17 patients had multifocal disease cal and endoscopic Endings are listed in table 3.Of note, in 1 in 20 renal units (average tumor size 1.92 cm.). Of the 20 patient ureteroscopic treatment of a 1 cm. grade 2 mid ure renal units 10 (50%) were rendered tumor-free, with subse- teral tumor was successful but the patient elected nephrourequent recurrences found in 3 (30%) at a mean followup of 29 terectomy to avoid ureteroscopic followup. Pathological months. At the most recent followup 9 of 10 tumor-free renal examination revealed no tumor (stage pTO). In a patient with a 2.5 cm. grade 2 renal pelvic tumor treated with comunits (90%) and 9 of 20 overall had no evidence of disease. Of 21 patients with 1 tumor (average size 1.39 cm.) 17 bined h0lmium:YAG and neodymium:YAG laser therapy (81%)were rendered tumor-free, with 5 of them (29%)having nephroureteredomy was recommended because of the size recurrences at a mean followup 40 months. At the most and grade of the tumor. Pathological examination showed recent followup 15 of the 17 tumor-free kidneys (88%) and 15 dysplasia and inverted papilloma but no frank carcinoma. of 21 overall (72%) had no evidence of disease. One patient had an increase in tumor grade on pathological Location. The largest primary tumor was in the distal examination, while the remaining 5 had excellent correlation ureter in 7 cases, mid ureter in 8,proximal ureter in 3,renal of biopsy and final pathological grades. We previously repelvis in 11,lower pole infundibulum or calix in 4 and upper ported a series of 51 patients undergoing open surgery after pole infundibdum or calix in 8. A total of 10 patients had ureteroscopic biopsy and found good correlation of ureteromultiple ipsilateral tumors at presentation. The location (in- scopic biopsy and final pathological grade as well as pathotrarenal versus ureteral) had no statistically significant ef- logical stage.17 fect on the initial tumor-free rate (71versus 67%) or recurComplications. Complications were generally related to rence rate (25versus 33%). In fact, the renal pelvic tumors underlying cardiopulmonary disease, including atrial fibrilwere more likely to have no evidence of disease a t most recent lation, congestive heart failure, arrhythmias and pulmonary followup (65.2versus 50961, which was not statistically sig- edema. One patient with a solitary kidney suffered an epinificant (p = 0.358). Average tumor size (1.60 versus 1.67 sode of postoperative acute renal failure with clot retention cm.)a t each location was also similar. The only notable but baseline renal function recovered. One patient suffered a difference between the 2 groups was the percentage of low cerebrovascular accident postoperatively. No patient regrade tumors, which was greater in the intrarenal group quired a blood transfusion or emergency open surgery for (59.1versus 44.4%). bleeding. No perforations were noted during the ureteroClassi&ation by indication. Indications for endoscopic scopic procedures. Two patients had ureteral strictures 1 treatment can be classified as absolute-patients would not with a history of pelvic radiation for bladder cancer and 1 tolerate open surgery or would require dialysis, relativeafter neodymium:YAG laser treatment of a proximal ureteral severe medical problems or multifocal disease, elective-no tumor. We presently prefer to treat tumors with a combinaTABLE2. Tumor gmde,sue and location, as well as grade, location and retrograde findings in 8 patients with recurrent transitional cell carcinoma ~~
Recurrences Initial Grade
Size (an.)
Mos%mu~enceDetected After Initial No Evidence of Disease
Initial Loeation No.
Grade
Location
1 1 1 2 1 1 7
Not available* Not available'
Not available Not available Renal pelvis Low ureter Low ureter Not available Ureter and renal pelvis Ureter and renal pelvis
~~~~
1
0.5 1.o 0.5 0.5
2
1.5
Low
2.0 3.0 2.0
Renal pelvis Renal pelvis Renal pelvie Low ureter Low ureter Proximal ureter Proximal ureter Proximal ureter
LOW
1 Not available' Not available* 1-2 2
2 Positive cytology findings only. t Abnormality not related to tumor in 4 cases. whiie normal findings were noted in 1 and filling defect in 2
~
21 42 53 38 13 7 21 18
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URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
TABLE3. Correlation of ureteroscopic biopsy grade, treatment modality and pathological findings i n 8 patients who icnderulent nephroureterectomy after ureteroscopic treatment . ~ -~ ~ ~ . ~ . ~ _ ~ _ _ _ _ _ ~ _ _ _ ~ ~ ~ ~~~
Location Size Icm.) Treatment ~-_ ~ _ _ 1.5, 0.5 Holmium:YAG laser Renal pelvis, ureter 1.0 Neodymium:YAG laser Upper pole Mid ureter 1.0 Neodymium:YAG laser 2.5 Upper pole Ho1mium:YAG laser, neodymium:YAG laser Fulyration Upper pole 1.0 Multiple 0.2 Fulguration Ureter, renal pelvis Fulguration Renal pelvis 0.5 Ureter. renal pelvis 2.0 Holmium:YAG laser. neodymium:YAG laser ___ ~ _ _ _ _ _ _ _ ~ . _ ~ _ ~
~~
~
~~
~
~
~~~~
~~~~
~~~
~~
~~~~
-
Cytology
Grade/Cell Block
Pathological Grdddstage -~
Pos. Pos. Pos. Pas. Pas. Pas. Pas. Pas.
1-2 1 2 2 2 Low grade 2 1
m 1 lma No tumor Inverted papilloma. dysplasia 1ma 1-m1 2-3m3 1ma
~~~~
~
~
~~
~~
~
_
_
_
~
~ ~.
-
~~
~~~-~
ratory, where cell blocks are prepared for any visible tissue fragments.s,li The diagnosis from the ureteroscopic biopsy has correlated well with final pathological grading and staging of nephroureterectomy specimens.1i This diagnostic accuracy, particularly of the grade, permits selection of patients who may be treated better with nephroureterectomy than those who can be treated and followed safely endoscopically. Others have previously shown that the prognosis of patients with transitional cell carcinoma of the upper urinary tract is related to the grade and stage of the lesion.20.21 Our experience with ureteroscopic treatment and followup of upper urinary tract tumors compares favorably with other series of endoscopic treatment.*-’* There has been a low rate of complications, no blood transfusions and no regional or distant metastatic disease. Several important results have been noted in this study. Again, we can relate the success in achieving a disease-free status and the recurrence rate to the grade of the tumor. Low grade tumors were more likely to be eradicated with fewer recurrences than higher grade tumors. Smaller tumors, particularly those smaller than 1.5 cm., were also more likely to be treated successfully. Multifocality also increased the risk of recurrence in the upper urinary tract or bladder. However, the initial location of the tumor, whether intrarenal or ureteral, had no effect on the tumorFree or recurrence rates. Although previous studies suggested a greater recurrence rate for tumors within the renal pelvis or intrarenal collecting system, t h e effect of tumor size or multifocality was not considered in those shorter series. DISCUSSION Therefore, we believe that the location is less important than Standard treatment for transitional cell carcinoma of the tumor multifocality, size and grade. It has been impossible to determine the stage of transitionupper urinary tract has been nephroureterectomy including a cuff of bladder. Greater recurrence rates have been noted al cell carcinoma in the upper urinary tract without extirpawhen a less extensive operation has been performed, partic- tion. Endoscopic biopsy cannot provide a full thickness samularly with more proximal lesions.’ However, some patients ple of the ureter or renal pelvis to allow microscopic are at risk for significant morbidity and mortality with a examination of the muscle for invasion. Preoperative radiomajor open operation or for chronic hemodialysis from the logical studies, such as computerized tomography, have inloss of renal function. These patients can be treated best with adequate resolution for accurate staging.”” There h a s been parenchymal sparing treatment, including conservative open some promise from the use of endo-luminal ultrasound but surgery or endoscopy. Distal ureterectomy has produced sat- the results a r e too premature to allow valid conclusions.2:l We Isfactory success rates for t h e treatment of transitional cell previously demonstrated good correlation between the grade of a tumor determined by ureteroscopic biopsy and the final carcinoma of the lower ureter.2 Developments in ureteroscopic instruments and tech- pathological stage in nephroureterectomy specimens.li niques now allow for endoscopic access to the entire upper Therefore, presently we can only inferentially determine the urinary tract. Small diameter rigid and flexible uretero- stage of upper urinary tract neoplasms treated endoscopiscopes have been combined with endoscopic biopsy tech- cally. An essential part of any conservative surgical modality is niques and devices for tissue ablation to offer practical approaches to upper urinary tract tumors. In particular. close followup. Since we found only a 25% sensitivity for the ho1mium:YAG and neodymium:YAG lasers delivered retrograde ureteropyelography in detecting recurrent upper through small diameter, flexible fibers have permitted treat- tract tumors, we can recommend complete endoscopic folment of relatively larger tumors while maintaining hemosta- lowup at regular intervals, much as in bladder cancer. In the sis.7.1~) present series we observed 18 recurrences in 8 patients, A major impediment to t h e appropriate endoscopic treat- including 3 at 38. 42 and 53 months after being rendered ment of upper urinary tract tumors has been the difficulty in disease-free. No recurrences have been high grade or unreobtaining accurate biopsies. Our ureteroscopic biopsy tech- sectable. After recurrences were found, patients were treated W u e s combined with improved handling of the specimens and followed every 8 to 12 weeks until disease-free and then with cfiopathological techniques have markedly improved placed back on the followup protocol. In comparison, in a the accuracy of diagnostic biopsy. O u r practice since 1989 has recent series patients with renal pelvic tumors treated perbeen to send all of the specimens to the cytopathology labo- cutaneously experienced recurrences in the renal pelvis (6)
tion of the neodymium:YAG laser for deeper coagulation and the ho1mium:YAG laser for direct tissue ablation. Of 2 patients who underwent nephroureterectomy l subsequently died of unrelated causes and 1 required dialysis 22 months later. Length of stay arid operative time. We currently treat patients on a n outpatient basis and hospitalize them only for postoperative mitomycin C instillation or medical difficulties. Average operative time for our last 20 cases was 100 minutes (range 50 to 150). Patients who underwent followup ureteroscopy without bleeding or need for ureteral dilation were discharged home without a stent, while most had a stent with a string attached. One patient with a solitary kidney undergoing uncomplicated followup ureteroscopy required placement of a stent after becoming anuric in the recovery room. One female patient with a distal ureteral tumor was followed in the office with semirigid ureteroscopy with local anesthesia. Postoperative treatment. Mitomycin C was administered via a ureteral catheter on 24 occasions in 15 patients judged to be at high risk for recurrence. No toxicity was attributable to the mitomycin C instillations. Seven patients received intravesical BCG with a ureteral stent in place. No toxicity was noted in these patients. As in a previous report of mitomycin C instillation,’a no attempt was made to randomize these patients. Consequently little can be determined regarding the efficacy of either treatment.
1564
URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
patients, such as those with bilateral disease or a solitary kidney. Low grade, low stage disease of the distal ureter also appears to be particularly well suited to this approach. In other patients, particularly those with bulky or high grade tients treated endoscopically should undergo endoscopic fol- lesions, this therapy may be suboptimal and should be done only with the full understanding and consent of the patient. lowup on a long-term and probably lifelong basis. A major concern raised by any conservative surgical treat- The success for the treatment of solitary low grade lesions is ment is the possibility of a greater risk for recurrence com- sufficient to offer it as elective therapy in patients with pared to standard radical extirpation. Nephroureterectomy normal renal function when they can completely understand has been the standard treatment for most upper urinary the risks and benefits, and provided adequate endoscopic tract transitional cell carcinomas, although low grade and followup can be maintained. Adjuvant mitomycin C or BCG stage distal ureteral tumors can be treated successfully with appears to be safe but its efficacy is unknown. Followup for distal ureterectomy.2 The recurrence rate for small, low recurrence should be considered an essential part of any plan grade upper urinary tract lesions in our series is sufficiently for endoscopic therapy. low to indicate the value of this therapy. Such nephron conserving therapy is particularly valuable in patients with a REFERENCES solitary or compromised contralateral kidney. The 11 pa1. Mazeman, E.: Tumours of the upper urinary calyces, renal peltients in whom endoscopic treatment was totally elective vis, and ureter. Eur. Urol., 2 120,1976. have had excellent success, with 10becoming tumor-free and 2 having 3 recurrences. Clearly, these patients have been se- 2. Zincke, H.and Neves, R. J.: Feasibility of conservative surgery for transitional cell cancer of the umer urinarv tract. Urol. lected with the expectation of a good result, which was achieved. Clin. N.h e r . , 11: 717,1984. Similarly, there does not appear to be a greater risk for 3. Abdel-Razzak. 0.and Badey, D. H.: The 6.9F semiri&d - ureterobladder recurrence than in series with surgical treatment or uBe. u k i & , 41: 451,1993. scope in previous reports of endoscopic therapy. Bladder tumors oc- 4. Grasso, M. and Bagley, D. H.:A 7.5/8.2F actively deflectable, curred in 33%of patients without and 45% with a history of flexible ureteroscope: a new device for both diagnostic and bladder cancer. Bladder tumor recurrence rates of 23 to 30% therapeutic upper urinary tract endoscopy. Urology, 43: 435, 1994. have been reported among patients treated with nephroure5. Bian, Y.,Ehya, H. and Bagley, D. H.:Cytologic diagnosis of terectomy or diatal ureterect.omy.20.21 In a previous summary upper urinary tract neoplasms by ureteroscopic sampling. of patients with ureteroscopic treatment of upper tract transActa Cytol., 39 733,1995. itional cell carcinoma 39% had a subsequent bladder tu6. Chaubal, A,McCue, P. A, Bagley, D. H. and Bibbo, M.: Multimor.16 Among those with a previous bladder tumor 50% had modal cytologic evaluation of upper urinary tract urothelial recurrences. Thus, there appears to be a high incidence of lesions. J. Surg. Path., 1:31, 1995. recurrent bladder tumors in these patients regardless of the 7. Bagley, D. H. and Erhard, M.: Use of the holmium laser in the therapy and the recurrence rate does not appear to be exacupper urinary tract. Tech. Urol.,1: 25,1995. erbated by endoscopic treatment. 8. Jarrett, T. W., Sweetser, P. M., Weiss, G. H. and Smith, A. D.: Percutaneous management of transitional cell carcinoma of Percutaneous endoscopic resection of tumors in the intrathe renal collecting system: 9-year experience. J. Urol., 15L: renal collecting system has also been reported recently,s with 1629,1995. advantages including the ability to treat larger lesions and to obtain sufficient material to stage some tumors pathological- 9. Tasca, A, Zattoni, F., Garbeglio, A., Villi, G., Bassi, P. and Meneghini, A: Endourologic treatment of transitional cell car1y.S-11 However, inherent in the percutaneous treatment is cinoma of the upper urinary tract. J. Endourol., 6 253,1992. the risk of complications related to access (hemorrhage, ex- 10. Streem, S. B. and Pontes, E. J.: Percutaneous management of travasation and seeding of the tract), which can be avoided upper tract transitional cell carcinoma. J. Urol., 135 773, with a retrograde approach. The length of hospitalization 1986. (greater than 4 days) and the need for patients to maintain a 11. Patel, A., Soonawalla, P., Shepherd, S. F., Dearnaley, D. P., Kellett, M. J. and Woodhouse, C. R. J.: Long-term outcome percutaneous nephrostomy tube for several weeks are addiaRer percutaneous treatment of transitional cell carcinoma of tional disadvantages.8 In comparison, with a ureteroscopic the renal pelvis. J. Urol., 1SS: 868,1996. approach we found an excellent correlation between ureteroscopic grade and pathological stage, which permits some 12. Huffman, J. L.,Morse, M. J., Bagley, D. H., Herr, H., Lyon, E. S. and Whitmore, W. F.,Jr.: Endoscopic diagnosis and treatment confidence in determining treatment options. However, in of upper-tract urothelial tumors. A preliminary report. Canour series there has been a significant limitation with the cer, 55: 1422,1985. ureteroscopic treatment of larger tumors (table 1).The ma- 13. Grossman, H.B.,Schwartz, S. L. and Konnak, J. W.: Ureterojority of ureteroscopic treatments can be completed on an scopic treatment of urothelial carcinoma of the ureter and outpatient basis. Extravasation and propagation of tumor renal pelvis. J. Urol., 148: 275, 1992. cells outside the urinary tract using the ureteroscopic ap- 14. Blute, M. L.,Segura, J. W., Patterson, D. E., Benson, R. C., Jr. and Zincke, H.: Impact of endourology on diagnosis and manproach have been suggested in 1 case report.= However, in a agement of upper urinary tract urothelial cancer. J. Urol., 141: previous series of nephroureterectomy specimens25 and in 1298,1989. the clinical course of our series extrarenal spread of tumor 15. Abdel-Razzak,0.M., Ehya, H., Cubler-Goodman,A. and Bagley, has not been observed. D. H.: Ureteroscopic biopsy in the upper urinary tract. Urol-
and ipsilateral ureter (2), 4 of which became large enough to require nephroureterectomy.1' The patients were followed with periodic excretory urography andlor retrograde ureteropyelography without endoscopy. Thus, we can state that pa-
__
CONCLUSIONS
The ureteroecopic treatment of upper urinary transitional cell carcinoma can be performed with minimal morbidity and an excellent success rate, and it should be considered a first choice for solitary, low grade tumors in a patient requiring a nephron sparing procedure. It also is possible to obtain satisfactory success rates even with larger tumors and in some patients with higher grade transitional cell carcinoma. Ureteroscopic treatment is now possible for many patients with transitional cell carcinoma of the upper urinary tract, and it may be the preferred treatment in high risk
ogy, 44:451,1994. 16. Bagley, D. H.: Ureteroscopic treatment of upper urinary tract neoplasms. In: Smith's Textbook of Endourology. Edited by A. D. Smith, G. H. Badlani and D. H. Bagley. St. Louis: Quality Medical Publishing, Inc., p. 474, 1996. 17. Keeley, F. X.,Kulp, D. A., Bibbo, M., McCue, P. A. and Bagley, D. H.: Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J . Urol., 157: 33, 1997. 18. Eastham, J. A. and Huffman, J . L.: Technique of mitomycin c instillation in the treatment of upper urinary tract urothelid tumors. J. Urol., 1 5 0 324,1993. 19. Razvi, H. A., Chun, S. S., Denstedt, J. D. and Sales, J. L.: Soft-tissue applications of the Ho1mium:YAG laser in urology. J. Endourol., 9: 387, 1995.
URETEROSCOPIC TREATMENT O F UPPER URINARY TRACT TRANSITIONAL CELL CANCER
20. Murphy, D. M., Zincke, H. and Furlow, W. L.: Primary grade I transitional cell carcinoma of the renal pelvis and ureter. J. Urol., 123: 629, 1980. 21. Murphy, D. M., Zincke, H. and Furlow, W. L.: Management ofhigh grade transitional cell cancer of the upper urinary tract. J. Urol., 125: 25, 1981. 22. Badalament. R.A., Bennett, W. F., Bova, J. G . , Kenworthy, P. R., Wise, H. A., Jr., Smith, S. and Perez, J.: Computed tomography of primary transitional cell carcinoma of the upper urinary tracts. Urology, 4 0 71, 1992.
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23. Liu, J. B., Bagley, D. H., Conlin, M. J., Merton, D. A,, Alexander, A. A. and Goldberg, B. B.: Endoluminal ultrasound evaluation of ureteral and renal pelvic neoplasms, J. Ultrasound Med., submitted for publication. 24. Lim, D. J., Shattuck, M. C. and Cock, W. A.: Pyelovenous lymphatic migration of transitional cell carcinoma following flexible ureterorenoscopy. J. Urol., 1 4 9 109, 1993. 25. Kulp, D. A. and Bagley, D. H.: Does flexible ureteropyeloscopy promote local recurrence of transitional cell carcinoma? J. Endourol., 8 111, 1994.
Vol. 157, 1560-1565,May 1997 Printed in U.SA,
THEJOURNAL OF UROLOGY Copyright 0 1997 by AMERICAYUROLOCICAL ASSCCLKT~ON. Isc
Original Articles URETEROSCOPIC TREATMENT AND SURVEILLANCE OF UPPER URINARY TFUCT TRANSITIONAL CELL CARCINOMA FRANCIS X. KEELEY, J R . , MARLUCE BIBBO
AND
DEMETRIUS H. BAGLEY
From the Departments of Urology, Radiology and Cytology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
ABSTRACT
Purpose: We determined the efficacy of ureteroscopic t r e a t m e n t of upper u r i n a r y t r a c t t r a n s itional cell carcinoma. Materials a n d Methods: Of 92 patients diagnosed with upper u r i n a r y t r a c t transitional cell carcinoma at o u r institution from 1985 t o 1995, 38 (41 kidneys) u n d e r w e n t ureteroscopic treatment and followup. Semirigid and flexible ureteroscopes were used t o examine the collecting system. T u m o r s were biopsied, and t r e a t e d w i t h fulguration, the neodymium:YAG laser and/or the ho1mium:YAG laser. Patients were t r e a t e d every 6 t o 12 weeks until tumor-free a n d then followed o n a strict endoscopic protocol. Results: Mean and m e d i a n followup w a s 35.1 a n d 26 months, respectively (range 3 t o 116). Grading of ureteroscopic biopsies w a s possible in 40 of 41 cases. Initial grading of tumors w a s low (grade 1 o r 1 t o 2) in 21 kidneys, grade 2 in 14 and grade 3 in 5. Of 41 ludneys 28 (68%)were documented as tumor-free ureteroscopically at some time following t r e a t m e n t , including 8 (29%) w i t h subsequent recurrences that were treated endoscopically a n d 24 (86%)with n o evidence of disease at the most recent followup. No p a t i e n t to d a t e has had progression of disease during endoscopic followup. High t u m o r grade, size a n d multifocality w e r e significantly associated w i t h t u m o r persistence a n d recurrence. Location in the kidney versus ureter w a s n o t a significant prognostic factor. Of the r e c u r r e n t t u m o r s 75% were n o t identified radiographically but were only discovered endoscopically. Two of 8 kidneys removed after endoscopic treatment had n o t u m o r stage (pTO). Conclusions: Endoscopic treatment of u p p e r u r i n a r y t r a c t transitional cell carcinoma is a reasonable method t o treat carefully select patients based on strict indications. Complete endoscopic followup at regular intervals is essential to rule out recurrences. KEYWORDS:carcinoma, transitional cell; kidney neoplasms; ureteral neoplasms; laser surgery Transitional cell carcinoma of the upper urinary tract is relatively uncommon, accounting for 2 to 5% of urothelial tumors. The standard treatment consisted of nephroureterectomy with a cuff of bladder, which was adopted due to the unacceptably high recurrence rate associated with more conservative procedures.' Nephron sparing surgery has been attempted in special circumstances, such as tumors in a solitary kidney or in patients with bilateral disease, but recurrence rates have been high. In contrast, low grade, low stage distal ureteral tumors can be treated with distal ureterectomy alone with a high cure rate.2 Endoscopic treatment of neoplasms of the upper urinary tract has become possible with the development of improved instrumentation. A combination of accurate endoscopic diagnosis with techniques for tissue ablation makes endoscopic therapy possible. Ureteroscopic techniques now allow access to the entire collecting system without prior dilation of the ureter.".4 Improved biopsy and cytopathological techniques have improved ureteroscopic diagnosis of upper urinary tract Accepted for publication November 8, 1996. Editor's Note: This article is the first of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1910 and 1911.
endoluminal lesions.5.6 The development of small diameter electrosurgical devices and lasers has allowed for precise ablation of tumors.7 Several investigators reported results of endoscopic percutaneous*-ll or uretero~copic,12-~4 treatment of upper urinary tract tumors. We present our experience with 41 kidneys in 38 patients with transitional cell carcinoma of the upper urinary tract treated with endoscopic resection and regular ureteroscopic followup. We also report the pathological findings of open surgical specimens from 8 patients initially treated endoscopically. PATIENTS AND METHODS
Of 92 patients diagnosed ureteroscopically with transitional cell carcinoma of the upper urinary tract from 1985 to 1995, 46 underwent purely diagnostic ureteroscopy followed by open extirpation, while 46 underwent some form of endoscopic treatment. Of the latter patients 8 underwent open surgery following endoscopic therapy, leaving 14 women and 24 men (mean age 70.9 years, range 45 t o 87) who were treated endoscopically and followed on our surveillance protocol. At least 1 followup ureteroscopic examination was done in all 38 patients. The right and left collecting systems were
1560
1561
URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
involved in 26 and 15 cases, respectively (3 had bilateral involvement). Patients with positive cytology results from the upper urinary tract without evidence of gross exophytic neoplasm were not included in this study. Patients presented with a variety of signs and symptoms, including gross hematuria (16),microscopic hematuria (4), filling defects found during followup of bladder cancer (8), flank pain secondary to obstruction (3)and cystoscopically detected tumor fronds in a ureteral orifice (6). All patients had a history of cigarette smoking. Evaluation included cystoscopy, retrograde ureteropyelography, semirigid and flexible ureteroscopy, and biopsy of any visible tumor. Tumor in the lower pole calix of 1patient was an incidental finding during antegrade (percutaneous) endopyelotomy. All other cases were diagnosed ureteroscopically. Specimens were obtained by aspiration, saline wash biopsy with cup forceps, flat wire basket or graspers; postbiopsy aspiration, and post-laser aspiration. Multiple specimens were obtained during each p r o c e d ~ r e . ~ ~ . ~ ~ Once transitional cell carcinoma was diagnosed in tissue patients were counseled on the risks and benefits of open versus endoscopic treatment. It was emphasized consistently that open surgery was the standard treatment for upper urinary tract transitional cell carcinoma. Endoscopy with followup was chosen by 38 patients for a variety of indications, including a solitary kidney (7)or bilateral disease (8), palliation (21, renal insufficiency (2), high medical risk for open surgery (8),preference (4) and small, low grade tumors
(7). Ureteroscopic treatment consisted of removal or ablation of tissue using electrosurgical devices, mechanical techniques and lasers. Since 1994 we have used a combination of needymium:YAG and ho1mium:YAG lasers for coagulation and ablation of tumors as described previously.'*l6 Select patients with multifocal, large or incompletely treated tumors received 40 mg. mitomycin C in 3 divided doses via a ureteral catheter in the immediate postoperative period. Some patients with significant bladder and upper urinary tract disease were treated with a standard course of intravesical bacillus Calmette-Guerin (BCG) with an indwelling ureteral stent. Patients were examined with cystoscopy and ureteroscopy 3 months after initial treatment. Persistent or recurrent tumor was treated and the patients were examined again 3 months later. When found endoscopically at the same site it was impossible to determine if the tumor was, in fact, persistent or recurrent. A lesion at another site could be considered a recurrence or new tumor. The decision for continued endoscopic therapy or nephmureteredomy was based on the size, location and grade of the lesion, as well as patient desire.
If there was no evidence of tumor patients were followed on the surveillance protocol. Patients with large tumors requiring debulking were treated a t more frequent intervals (every 6 to 12 weeks) until tumor-free or a decision was made for other treatment. Followup consisted of cystoscopy and cytology at 3-month intervals, retrograde ureteropyelography and ureteroscopy at 6-month intervals, and imaging of the contralateral kidney at 12-month intervals. Several patients with severe medical problems were followed on a less rigorous schedule. Of the patients 11 were followed by a local urologist after a mean of 45 months of surveillance at our institution. Each patient was recently contacted and the records were reviewed. Recurrence was defined as grossly visible tumor on ureteroscopy andor a positive cytology study. Statistical analysis was performed with Fisher's exact test. RESULTS
During a 10-year period 49 renal units in 46 patients were treated endoscopically: 41 renal units in 38 patients who underwent only endoscopic treatment were followed endoscopically for a t least 3 months (mean 35.1, median 26, range 3 to 116)and 8 patients underwent nephroureterectomy after endoscopic treatment. Tumors were treated on a t least 90 separate occasions, with more than 200 ureteroscopic procedures being performed in these patients. Treatment consisted of fulguration only in 19 cases, ne0dymium:YAG laser only in 23, h0lmium:YAG laser only in 22 and combinations of each in 26. Of the renal units 28 (68%)were rendered tumor-free after an average of 1.57 ureteroscopic treatments (median 1,range 1to 6), including 8 (29%) that had recurrences.At the most recent followup 24 of the 28 tumor-free renal units (86%)had no evidence of disease, including 9 of 10 (90%)cases followed for at least 5 years. Overall, 24 of 41 renal units (59%) had no evidence of disease. No patient to date has suffered local or metastatic progression of disease during followup and none has had a bulky recurrence necessitating extirpation. Trrmor grade. Every patient had transitional cell carcinoma documented by positive cytology results. Grading of ureteroscopic biopsies by routine histopathological analysis, cell block technique or Cytospin tests was documented in 40 of 41 cases (table 1).One patient without disease grade had a 1 cm. papillary tumor in an upper pole calix and was followed for 82 months without recurrence. Low grade tumors (grade 1 or 1 and 2) were found in 21 renal units in 19 patienta (tumor size 0.5 to 3 cm.,mean 1.57). Of21 renal units 16 (76%)were rendered tumor-& at some time, including 4 (25%) that had recurrences with a mean followup of 40.3 months. At the most recent followup 15
TABLE1. Comparison of patients by tumor gmde,tumor size and indication versus disease-free and recurrence mtes No. Kidneys
No. TumorFree (%)
No Evidence of Disease
No. Reeurrenees
No. Pta.
%Au
(%)
(%)
Pts.
Mean Followup (mos.)
Grade:
LOW
21 14 5 41t
2 3
16 (76) 9 (64)
28 (68) Totals Tumor size (cm.): Less than 1.5 20 (91) 22 More than 1.5 19 7 (36) Indication: Elective 11 10 (91) Relative 8 7 (87) Absolute 20 10 (50) 2 160) Palliative * Followup was too short to amwas recurrence rate. f One patient had a tumor without a grade. $ Only 6 patienta had adequate followup for conaideration of recurrence. ~
4 (25.7) 4 (44.4)
-* -
15 (94) 6 (66) 2 (100) 24 (86)
5 (25) 3 (50)$
20 (91) 4 (21)
8
2 2 4
(29)
(20) (29)
(40)
-*
9 6 8 1
71 43
40 -
40.3 27.6 21
59
(82) (76)
60
(40) (60)
34
25
-
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URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
of 16 tumor-free renal units (94%)and 15 of 21 overall (71%) contraindication to definitive extirpation and palliativehad no evidence of disease. Grade 2 tumors occurred in 14 large, bleeding tumors in patients who would not tolerate renal units in 14 patients (tumor size 0.5 to 3 cm., mean open surgery. As expected, patients treated for elective or 1.88).Of 14 renal units 9 (64%)were rendered tumor-free a t relative indications had a high 1ikeWlood of becoming tumorsome time, including 4 (44%)that had recurrences with a free as well as low recurrence rates, while those with absomean followup of 27.6 months. At the most recent followup 6 lute or palliative indications fared worse (table 1). Incidence of bladder tumors. O v e r d 20 patients (53%)had of 9 tumor-free renal units (66%)and 6 of 14 overall (43%) had no evidence of disease. Grade 3 tumors were noted in 5 a history of transitional cell carcinoma of the bladder at renal units in 4 patients (tumor size 0.5to 3 cm., mean 2.1). diagnosis. Bladder tumors occurred during followup in 15 Two renal units were rendered disease-free. Followup was patients (40%),including 9 of 20 (45%)with and 6 of 18 (33%) too short to assess recurrence rates. Two kidneys had no without a history of transitional cell carcinoma of the bladder. Of the patients with such a history 7 were treated with evidence of disease a t the most recent followup. Tumor size. The size of the tumor correlated strongly with intravesical BCG during followup and 1 had invasive transtreatment success (table 1). Only 7 of 19 renal units (36%) itional cell carcinoma of the bladder. Accuracy of retrograde ureteropyehgruphy. Overall there with tumors larger than 1.5 ern. were ever rendered tumorfree, and 3 of 6 tumor-free renal units (50%) with adequate were 16 recurrences in 8 patients who at some point had been followup subsequently had recurrence. At the most recent fol- tumor-free (table 2). Only 4 recurrences were noted on retlowup (mean 22 months) 4 of 7 tumor-free renal units (57%) rograde ureteropyelography, so that the sensitivity in diagand only 4 of 19 collecting systems (21%) had no evidence of nosing recurrences was only 25%. Additional abnormalities disease. In contrast, 20 of 22 renal units (91%) with initial not related to recurrence were found on 4 retrograde studies, tumors no larger than 1.5 cm.have ever been rendered tumor- while 8 were read as normal. Pathological findings after open surgery. Of the patients 8 free and only 5 (25%) tumor-free kidneys had recurrences. At the most recent followup (mean 45 months) all 20 tumor-free underwent open extirpation after ureteroscopic treatment renal units (100%) and 20 of 22 collectingsystems overall (91%) due to high volume disease (2),persistent disease (4) or patient choice (2).The ureteroscopie biopsy, final pathologihad no evidence of disease. Multifocality. A total of 17 patients had multifocal disease cal and endoscopic Endings are listed in table 3.Of note, in 1 in 20 renal units (average tumor size 1.92 cm.). Of the 20 patient ureteroscopic treatment of a 1 cm. grade 2 mid ure renal units 10 (50%) were rendered tumor-free, with subse- teral tumor was successful but the patient elected nephrourequent recurrences found in 3 (30%) at a mean followup of 29 terectomy to avoid ureteroscopic followup. Pathological months. At the most recent followup 9 of 10 tumor-free renal examination revealed no tumor (stage pTO). In a patient with a 2.5 cm. grade 2 renal pelvic tumor treated with comunits (90%) and 9 of 20 overall had no evidence of disease. Of 21 patients with 1 tumor (average size 1.39 cm.) 17 bined h0lmium:YAG and neodymium:YAG laser therapy (81%)were rendered tumor-free, with 5 of them (29%)having nephroureteredomy was recommended because of the size recurrences at a mean followup 40 months. At the most and grade of the tumor. Pathological examination showed recent followup 15 of the 17 tumor-free kidneys (88%) and 15 dysplasia and inverted papilloma but no frank carcinoma. of 21 overall (72%) had no evidence of disease. One patient had an increase in tumor grade on pathological Location. The largest primary tumor was in the distal examination, while the remaining 5 had excellent correlation ureter in 7 cases, mid ureter in 8,proximal ureter in 3,renal of biopsy and final pathological grades. We previously repelvis in 11,lower pole infundibulum or calix in 4 and upper ported a series of 51 patients undergoing open surgery after pole infundibdum or calix in 8. A total of 10 patients had ureteroscopic biopsy and found good correlation of ureteromultiple ipsilateral tumors at presentation. The location (in- scopic biopsy and final pathological grade as well as pathotrarenal versus ureteral) had no statistically significant ef- logical stage.17 fect on the initial tumor-free rate (71versus 67%) or recurComplications. Complications were generally related to rence rate (25versus 33%). In fact, the renal pelvic tumors underlying cardiopulmonary disease, including atrial fibrilwere more likely to have no evidence of disease a t most recent lation, congestive heart failure, arrhythmias and pulmonary followup (65.2versus 50961, which was not statistically sig- edema. One patient with a solitary kidney suffered an epinificant (p = 0.358). Average tumor size (1.60 versus 1.67 sode of postoperative acute renal failure with clot retention cm.)a t each location was also similar. The only notable but baseline renal function recovered. One patient suffered a difference between the 2 groups was the percentage of low cerebrovascular accident postoperatively. No patient regrade tumors, which was greater in the intrarenal group quired a blood transfusion or emergency open surgery for (59.1versus 44.4%). bleeding. No perforations were noted during the ureteroClassi&ation by indication. Indications for endoscopic scopic procedures. Two patients had ureteral strictures 1 treatment can be classified as absolute-patients would not with a history of pelvic radiation for bladder cancer and 1 tolerate open surgery or would require dialysis, relativeafter neodymium:YAG laser treatment of a proximal ureteral severe medical problems or multifocal disease, elective-no tumor. We presently prefer to treat tumors with a combinaTABLE2. Tumor gmde,sue and location, as well as grade, location and retrograde findings in 8 patients with recurrent transitional cell carcinoma ~~
Recurrences Initial Grade
Size (an.)
Mos%mu~enceDetected After Initial No Evidence of Disease
Initial Loeation No.
Grade
Location
1 1 1 2 1 1 7
Not available* Not available'
Not available Not available Renal pelvis Low ureter Low ureter Not available Ureter and renal pelvis Ureter and renal pelvis
~~~~
1
0.5 1.o 0.5 0.5
2
1.5
Low
2.0 3.0 2.0
Renal pelvis Renal pelvis Renal pelvie Low ureter Low ureter Proximal ureter Proximal ureter Proximal ureter
LOW
1 Not available' Not available* 1-2 2
2 Positive cytology findings only. t Abnormality not related to tumor in 4 cases. whiie normal findings were noted in 1 and filling defect in 2
~
21 42 53 38 13 7 21 18
1563
URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
TABLE3. Correlation of ureteroscopic biopsy grade, treatment modality and pathological findings i n 8 patients who icnderulent nephroureterectomy after ureteroscopic treatment . ~ -~ ~ ~ . ~ . ~ _ ~ _ _ _ _ _ ~ _ _ _ ~ ~ ~ ~~~
Location Size Icm.) Treatment ~-_ ~ _ _ 1.5, 0.5 Holmium:YAG laser Renal pelvis, ureter 1.0 Neodymium:YAG laser Upper pole Mid ureter 1.0 Neodymium:YAG laser 2.5 Upper pole Ho1mium:YAG laser, neodymium:YAG laser Fulyration Upper pole 1.0 Multiple 0.2 Fulguration Ureter, renal pelvis Fulguration Renal pelvis 0.5 Ureter. renal pelvis 2.0 Holmium:YAG laser. neodymium:YAG laser ___ ~ _ _ _ _ _ _ _ ~ . _ ~ _ ~
~~
~
~~
~
~
~~~~
~~~~
~~~
~~
~~~~
-
Cytology
Grade/Cell Block
Pathological Grdddstage -~
Pos. Pos. Pos. Pas. Pas. Pas. Pas. Pas.
1-2 1 2 2 2 Low grade 2 1
m 1 lma No tumor Inverted papilloma. dysplasia 1ma 1-m1 2-3m3 1ma
~~~~
~
~
~~
~~
~
_
_
_
~
~ ~.
-
~~
~~~-~
ratory, where cell blocks are prepared for any visible tissue fragments.s,li The diagnosis from the ureteroscopic biopsy has correlated well with final pathological grading and staging of nephroureterectomy specimens.1i This diagnostic accuracy, particularly of the grade, permits selection of patients who may be treated better with nephroureterectomy than those who can be treated and followed safely endoscopically. Others have previously shown that the prognosis of patients with transitional cell carcinoma of the upper urinary tract is related to the grade and stage of the lesion.20.21 Our experience with ureteroscopic treatment and followup of upper urinary tract tumors compares favorably with other series of endoscopic treatment.*-’* There has been a low rate of complications, no blood transfusions and no regional or distant metastatic disease. Several important results have been noted in this study. Again, we can relate the success in achieving a disease-free status and the recurrence rate to the grade of the tumor. Low grade tumors were more likely to be eradicated with fewer recurrences than higher grade tumors. Smaller tumors, particularly those smaller than 1.5 cm., were also more likely to be treated successfully. Multifocality also increased the risk of recurrence in the upper urinary tract or bladder. However, the initial location of the tumor, whether intrarenal or ureteral, had no effect on the tumorFree or recurrence rates. Although previous studies suggested a greater recurrence rate for tumors within the renal pelvis or intrarenal collecting system, t h e effect of tumor size or multifocality was not considered in those shorter series. DISCUSSION Therefore, we believe that the location is less important than Standard treatment for transitional cell carcinoma of the tumor multifocality, size and grade. It has been impossible to determine the stage of transitionupper urinary tract has been nephroureterectomy including a cuff of bladder. Greater recurrence rates have been noted al cell carcinoma in the upper urinary tract without extirpawhen a less extensive operation has been performed, partic- tion. Endoscopic biopsy cannot provide a full thickness samularly with more proximal lesions.’ However, some patients ple of the ureter or renal pelvis to allow microscopic are at risk for significant morbidity and mortality with a examination of the muscle for invasion. Preoperative radiomajor open operation or for chronic hemodialysis from the logical studies, such as computerized tomography, have inloss of renal function. These patients can be treated best with adequate resolution for accurate staging.”” There h a s been parenchymal sparing treatment, including conservative open some promise from the use of endo-luminal ultrasound but surgery or endoscopy. Distal ureterectomy has produced sat- the results a r e too premature to allow valid conclusions.2:l We Isfactory success rates for t h e treatment of transitional cell previously demonstrated good correlation between the grade of a tumor determined by ureteroscopic biopsy and the final carcinoma of the lower ureter.2 Developments in ureteroscopic instruments and tech- pathological stage in nephroureterectomy specimens.li niques now allow for endoscopic access to the entire upper Therefore, presently we can only inferentially determine the urinary tract. Small diameter rigid and flexible uretero- stage of upper urinary tract neoplasms treated endoscopiscopes have been combined with endoscopic biopsy tech- cally. An essential part of any conservative surgical modality is niques and devices for tissue ablation to offer practical approaches to upper urinary tract tumors. In particular. close followup. Since we found only a 25% sensitivity for the ho1mium:YAG and neodymium:YAG lasers delivered retrograde ureteropyelography in detecting recurrent upper through small diameter, flexible fibers have permitted treat- tract tumors, we can recommend complete endoscopic folment of relatively larger tumors while maintaining hemosta- lowup at regular intervals, much as in bladder cancer. In the sis.7.1~) present series we observed 18 recurrences in 8 patients, A major impediment to t h e appropriate endoscopic treat- including 3 at 38. 42 and 53 months after being rendered ment of upper urinary tract tumors has been the difficulty in disease-free. No recurrences have been high grade or unreobtaining accurate biopsies. Our ureteroscopic biopsy tech- sectable. After recurrences were found, patients were treated W u e s combined with improved handling of the specimens and followed every 8 to 12 weeks until disease-free and then with cfiopathological techniques have markedly improved placed back on the followup protocol. In comparison, in a the accuracy of diagnostic biopsy. O u r practice since 1989 has recent series patients with renal pelvic tumors treated perbeen to send all of the specimens to the cytopathology labo- cutaneously experienced recurrences in the renal pelvis (6)
tion of the neodymium:YAG laser for deeper coagulation and the ho1mium:YAG laser for direct tissue ablation. Of 2 patients who underwent nephroureterectomy l subsequently died of unrelated causes and 1 required dialysis 22 months later. Length of stay arid operative time. We currently treat patients on a n outpatient basis and hospitalize them only for postoperative mitomycin C instillation or medical difficulties. Average operative time for our last 20 cases was 100 minutes (range 50 to 150). Patients who underwent followup ureteroscopy without bleeding or need for ureteral dilation were discharged home without a stent, while most had a stent with a string attached. One patient with a solitary kidney undergoing uncomplicated followup ureteroscopy required placement of a stent after becoming anuric in the recovery room. One female patient with a distal ureteral tumor was followed in the office with semirigid ureteroscopy with local anesthesia. Postoperative treatment. Mitomycin C was administered via a ureteral catheter on 24 occasions in 15 patients judged to be at high risk for recurrence. No toxicity was attributable to the mitomycin C instillations. Seven patients received intravesical BCG with a ureteral stent in place. No toxicity was noted in these patients. As in a previous report of mitomycin C instillation,’a no attempt was made to randomize these patients. Consequently little can be determined regarding the efficacy of either treatment.
1564
URETEROSCOPIC TREATMENT OF UPPER URINARY TRACT TRANSITIONAL CELL CANCER
patients, such as those with bilateral disease or a solitary kidney. Low grade, low stage disease of the distal ureter also appears to be particularly well suited to this approach. In other patients, particularly those with bulky or high grade tients treated endoscopically should undergo endoscopic fol- lesions, this therapy may be suboptimal and should be done only with the full understanding and consent of the patient. lowup on a long-term and probably lifelong basis. A major concern raised by any conservative surgical treat- The success for the treatment of solitary low grade lesions is ment is the possibility of a greater risk for recurrence com- sufficient to offer it as elective therapy in patients with pared to standard radical extirpation. Nephroureterectomy normal renal function when they can completely understand has been the standard treatment for most upper urinary the risks and benefits, and provided adequate endoscopic tract transitional cell carcinomas, although low grade and followup can be maintained. Adjuvant mitomycin C or BCG stage distal ureteral tumors can be treated successfully with appears to be safe but its efficacy is unknown. Followup for distal ureterectomy.2 The recurrence rate for small, low recurrence should be considered an essential part of any plan grade upper urinary tract lesions in our series is sufficiently for endoscopic therapy. low to indicate the value of this therapy. Such nephron conserving therapy is particularly valuable in patients with a REFERENCES solitary or compromised contralateral kidney. The 11 pa1. Mazeman, E.: Tumours of the upper urinary calyces, renal peltients in whom endoscopic treatment was totally elective vis, and ureter. Eur. Urol., 2 120,1976. have had excellent success, with 10becoming tumor-free and 2 having 3 recurrences. Clearly, these patients have been se- 2. Zincke, H.and Neves, R. J.: Feasibility of conservative surgery for transitional cell cancer of the umer urinarv tract. Urol. lected with the expectation of a good result, which was achieved. Clin. N.h e r . , 11: 717,1984. Similarly, there does not appear to be a greater risk for 3. Abdel-Razzak. 0.and Badey, D. H.: The 6.9F semiri&d - ureterobladder recurrence than in series with surgical treatment or uBe. u k i & , 41: 451,1993. scope in previous reports of endoscopic therapy. Bladder tumors oc- 4. Grasso, M. and Bagley, D. H.:A 7.5/8.2F actively deflectable, curred in 33%of patients without and 45% with a history of flexible ureteroscope: a new device for both diagnostic and bladder cancer. Bladder tumor recurrence rates of 23 to 30% therapeutic upper urinary tract endoscopy. Urology, 43: 435, 1994. have been reported among patients treated with nephroure5. Bian, Y.,Ehya, H. and Bagley, D. H.:Cytologic diagnosis of terectomy or diatal ureterect.omy.20.21 In a previous summary upper urinary tract neoplasms by ureteroscopic sampling. of patients with ureteroscopic treatment of upper tract transActa Cytol., 39 733,1995. itional cell carcinoma 39% had a subsequent bladder tu6. Chaubal, A,McCue, P. A, Bagley, D. H. and Bibbo, M.: Multimor.16 Among those with a previous bladder tumor 50% had modal cytologic evaluation of upper urinary tract urothelial recurrences. Thus, there appears to be a high incidence of lesions. J. Surg. Path., 1:31, 1995. recurrent bladder tumors in these patients regardless of the 7. Bagley, D. H. and Erhard, M.: Use of the holmium laser in the therapy and the recurrence rate does not appear to be exacupper urinary tract. Tech. Urol.,1: 25,1995. erbated by endoscopic treatment. 8. Jarrett, T. W., Sweetser, P. M., Weiss, G. H. and Smith, A. D.: Percutaneous management of transitional cell carcinoma of Percutaneous endoscopic resection of tumors in the intrathe renal collecting system: 9-year experience. J. Urol., 15L: renal collecting system has also been reported recently,s with 1629,1995. advantages including the ability to treat larger lesions and to obtain sufficient material to stage some tumors pathological- 9. Tasca, A, Zattoni, F., Garbeglio, A., Villi, G., Bassi, P. and Meneghini, A: Endourologic treatment of transitional cell car1y.S-11 However, inherent in the percutaneous treatment is cinoma of the upper urinary tract. J. Endourol., 6 253,1992. the risk of complications related to access (hemorrhage, ex- 10. Streem, S. B. and Pontes, E. J.: Percutaneous management of travasation and seeding of the tract), which can be avoided upper tract transitional cell carcinoma. J. Urol., 135 773, with a retrograde approach. The length of hospitalization 1986. (greater than 4 days) and the need for patients to maintain a 11. Patel, A., Soonawalla, P., Shepherd, S. F., Dearnaley, D. P., Kellett, M. J. and Woodhouse, C. R. J.: Long-term outcome percutaneous nephrostomy tube for several weeks are addiaRer percutaneous treatment of transitional cell carcinoma of tional disadvantages.8 In comparison, with a ureteroscopic the renal pelvis. J. Urol., 1SS: 868,1996. approach we found an excellent correlation between ureteroscopic grade and pathological stage, which permits some 12. Huffman, J. L.,Morse, M. J., Bagley, D. H., Herr, H., Lyon, E. S. and Whitmore, W. F.,Jr.: Endoscopic diagnosis and treatment confidence in determining treatment options. However, in of upper-tract urothelial tumors. A preliminary report. Canour series there has been a significant limitation with the cer, 55: 1422,1985. ureteroscopic treatment of larger tumors (table 1).The ma- 13. Grossman, H.B.,Schwartz, S. L. and Konnak, J. W.: Ureterojority of ureteroscopic treatments can be completed on an scopic treatment of urothelial carcinoma of the ureter and outpatient basis. Extravasation and propagation of tumor renal pelvis. J. Urol., 148: 275, 1992. cells outside the urinary tract using the ureteroscopic ap- 14. Blute, M. L.,Segura, J. W., Patterson, D. E., Benson, R. C., Jr. and Zincke, H.: Impact of endourology on diagnosis and manproach have been suggested in 1 case report.= However, in a agement of upper urinary tract urothelial cancer. J. Urol., 141: previous series of nephroureterectomy specimens25 and in 1298,1989. the clinical course of our series extrarenal spread of tumor 15. Abdel-Razzak,0.M., Ehya, H., Cubler-Goodman,A. and Bagley, has not been observed. D. H.: Ureteroscopic biopsy in the upper urinary tract. Urol-
and ipsilateral ureter (2), 4 of which became large enough to require nephroureterectomy.1' The patients were followed with periodic excretory urography andlor retrograde ureteropyelography without endoscopy. Thus, we can state that pa-
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CONCLUSIONS
The ureteroecopic treatment of upper urinary transitional cell carcinoma can be performed with minimal morbidity and an excellent success rate, and it should be considered a first choice for solitary, low grade tumors in a patient requiring a nephron sparing procedure. It also is possible to obtain satisfactory success rates even with larger tumors and in some patients with higher grade transitional cell carcinoma. Ureteroscopic treatment is now possible for many patients with transitional cell carcinoma of the upper urinary tract, and it may be the preferred treatment in high risk
ogy, 44:451,1994. 16. Bagley, D. H.: Ureteroscopic treatment of upper urinary tract neoplasms. In: Smith's Textbook of Endourology. Edited by A. D. Smith, G. H. Badlani and D. H. Bagley. St. Louis: Quality Medical Publishing, Inc., p. 474, 1996. 17. Keeley, F. X.,Kulp, D. A., Bibbo, M., McCue, P. A. and Bagley, D. H.: Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J . Urol., 157: 33, 1997. 18. Eastham, J. A. and Huffman, J . L.: Technique of mitomycin c instillation in the treatment of upper urinary tract urothelid tumors. J. Urol., 1 5 0 324,1993. 19. Razvi, H. A., Chun, S. S., Denstedt, J. D. and Sales, J. L.: Soft-tissue applications of the Ho1mium:YAG laser in urology. J. Endourol., 9: 387, 1995.
URETEROSCOPIC TREATMENT O F UPPER URINARY TRACT TRANSITIONAL CELL CANCER
20. Murphy, D. M., Zincke, H. and Furlow, W. L.: Primary grade I transitional cell carcinoma of the renal pelvis and ureter. J. Urol., 123: 629, 1980. 21. Murphy, D. M., Zincke, H. and Furlow, W. L.: Management ofhigh grade transitional cell cancer of the upper urinary tract. J. Urol., 125: 25, 1981. 22. Badalament. R.A., Bennett, W. F., Bova, J. G . , Kenworthy, P. R., Wise, H. A., Jr., Smith, S. and Perez, J.: Computed tomography of primary transitional cell carcinoma of the upper urinary tracts. Urology, 4 0 71, 1992.
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23. Liu, J. B., Bagley, D. H., Conlin, M. J., Merton, D. A,, Alexander, A. A. and Goldberg, B. B.: Endoluminal ultrasound evaluation of ureteral and renal pelvic neoplasms, J. Ultrasound Med., submitted for publication. 24. Lim, D. J., Shattuck, M. C. and Cock, W. A.: Pyelovenous lymphatic migration of transitional cell carcinoma following flexible ureterorenoscopy. J. Urol., 1 4 9 109, 1993. 25. Kulp, D. A. and Bagley, D. H.: Does flexible ureteropyeloscopy promote local recurrence of transitional cell carcinoma? J. Endourol., 8 111, 1994.