Ini J Rndmrwn Oncolqy Bml. Phw Vol. Printed in the US A All nghts reserved.
t .Xl
036%3016/92 $5.00 Copyright 0 IW? Pergamon Press Ltd.
24. PP. 743-145
??Brief Communication
ADJUVANT RADIOTHERAPY IN HIGH STAGE TRANSITIONAL CARCINOMA OF THE RENAL PELVIS AND URETER
CELL
SCOTTC.
COZAD, D.D.S., M.D.,’ STEPHEN R. SMALLEY, M.D., * MARK AUSTENFELD, M.D.,2 MARK NOBLE, M.D.,2 SCOTT JENNINGS, M.D.* AND RALPH REYMOND, M.D.3
‘Departmentof Radiation Oncology, ‘Department of Urology, University of Kansas Medical Center, Kansas City, KS; and 3Department of Radiation Oncology, St. Francis Hospital, Topeka, KS
This review was undertakento assess the influenceof adjuvantradiationtherapyon failure patternsand survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-fourpatients with transitionalcell carcinomaof the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 NO/+, MO disease and underwent curative resections (median follow-up 13.5 months, range 331 I). Local failure was defined as recurrence in the tumor bed, regional nodes, or ureteral stump. Time to recurrence and survival were calculated from the time of pathologic diagnosis. Variables associated with local failure, distant metastasis, and survival were analyzed using univariate and multivariate analysis. Seventeen received surgery only, nine received adjuvant radiation therapy (median dose 50 Gy). Local failure occurred in 9 of 17 without and 1 of 9 with adjuvant radiation therapy (p = 0.07). Actuarial S-year local control was 34% without and 88% with adjuvant radiation therapy. Cox step-wise regression confirmed adjuvant radiation therapy (p = 0.006) and grade (p = 0.006) as significantly associated with local failure. No patients with low grade lesions suffered local failure either with or without adjuvant radiation therapy. High grade lesions had an local failure rate of 15%with and 71%withoutadjuvantradiationtherapy.Metastaticdisease occurredin 4 of 9 and 8 of 17 with and without radiation therapy. No significant factors influencing distant failure were identified. Five-year actuarial survival was 44% with and 24% without adjuvant radiation therapy. The survival differences were not statistically significant on univariate or multivariate analysis. High staged transitional cell carcinoma of the renal pelvis or ureter has a substantial local failure risk after surgery alone. Adjuvant radiation therapy markedly reduces this risk but has no impact on distant disease which occurs in approximately 50%. Effective adjuvant therapy will require effective systemic therapy in addition to adjuvant radiation therapy. Transitional cell carcinoma, Renal pelvis, Ureter, Radiotherapy.
eluding type of surgical procedure and use of adjuvant RT or chemotherapy (CT) was collected (3). All were free of gross residual or metastatic disease following resection. Continuous course adjuvant RT was administered to nine with a median dose of 50 Gy (range 37.4 to 56.0). A variety of techniques were used including opposed AP/PA in four, AP/PA with a lateral field in one, posterior wedged pairs with a PA boost in one, PA and lateral in one, 360” rotational in one, and unknown fields in one. All were treated with megavoltage energies. In seven cases, treatment volume was known from port films or diagrams. Six of these had only the tumor bed (i.e., renal fossa or ureteral bed) included in the field. Local failure (LF) was defined as recurrence in the tumor bed, regional nodes, or in the ureteral stump. TCC of the bladder or contralateral renal pelvis and ureter were considered second primaries. The time to recurrence and survival were calculated from the time of histologic diagnosis. Median follow-up was 13 months (range 3-3 11).
INTRODUCl3ON The use of radiation in the treatment of transitional cell carcinoma (TCC) of the renal pelvis or ureter has proponents and detractors (1, 2, 4-6, 8, 11, 12). Many of these are based on poorly defined populations, and include recurrent or palliatively treated cases. This review will describe the outcome for high stage TCC resected for cure treated with or without adjuvant radiation therapy (RT). METHODS
AND MATERIALS
Twenty-six cases of TCC resected for cure and having American Joint Commission (AJC) pathologic Stage III or IV by virtue of positive nodes, were identified in the Medical Records at the University of Kansas Medical Center or the St. Francis Hospital in Topeka, Kansas. Information regarding patient age and gender, tumor histology, grade, size and nodal status, presence of close (~5 mm) or positive microscopic residual, and therapy in-
Accepted for publication
Reprint requests to: Dr. S. C. Cozad. 743
12 May 1992
744
I. J. Radiation Oncology 0 Biology 0 Physics
Survival and failure curves were generated for the variablesgender, age (80), grade (I and 2 vs 3 and 4), adjuvant RT, surgical procedure (nephroureterectomy with bladder cuff vs all others) and close or positive microscopic residual using the KaplanMeier actuarial method (9). The significance of individual variables were tested using the generalized Savage (MantleCox) test (10). Multivariate analysis with the same variables was performed using the Cox step-wise method (7).
Table 1. Probability of local recurrence by grade and use of adjuvant RT in high stage patients Local recurrence
Adjuvant
RT
Grade
Yes No Yes No
o/4 o/4 115 9/13
Low Low High Hiah
three cases treated adjuvantly failed compared to both not receiving adjuvant RT.
RESULTS
The median ages of the adjuvant RT and surgery groups were 7 1 and 68, respectively. Six of nine adjuvant patients were male versus 12 of 17 treated surgically. Five and 13 high grade lesions were seen in the two groups. The adjuvant RT group had three cases in which there were close margins or microscopic residual disease. Two such cases were found in the surgery only group. Six patients received less than a total nephroureterectomy in the surgery group compared to one in the adjuvant RT. None of these patient, tumor, or treatment parameters was significantly different between the two groups. Local recurrence Local recurrence occurred in 10 cases and was always a component of initial failure. The absolute number of local recurrences were 9 of 17 and 1 of 9 for the surgery only and adjuvantly treated groups. Actuarial rates at 5 years are 34% and 88%, respectively (Fig. 1). The difference is of borderline significance by the Savage (Mantel Cox) test with a value ofp = 0.07. Controlling for the variables age, sex, adjuvant RT, surgical procedure, grade, and closer microscopic residual disease, only the use of adjuvant RT (p = 0.006) and grade (p = 0.006) were significant factors influencing local recurrence. Table 1 shows the probability of local recurrence by grade and use of adjuvant RT in these high stage patients. The presence of close margins or microscopic residual disease did not effect local control, however, none of the
Yes
Volume 24, Number 4, 1992
Metastasis Overall, 14 of 26 developed metastasis, 12 as a component of initial failure. In the group receiving adjuvant RT, 4 of 9 developed metastasis compared to 10 of 17 treated surgically. There were no significant tumor or treatment parameters effecting the development of metastasis. Survival Twenty of 26 patients have died. The absolute and 5year actuarial rates are 5 of 9 and 44% for those treated adjuvantly compared to 2 of 17 and 24% for those treated surgically (Fig. 2). This was not significant (p = 0.23). Controlling for age, sex, surgical procedure, and grade, adjuvant therapy continued to be without significance (p = 0.14) and no other variables became significant. DISCUSSION
This review contains 26 stage T3 cases of TCC of the renal pelvis or ureter. Only nine were treated with adjuvant RT. However, inspite of the small number of patients, local control was statistically significantly improved from 34% to 88%. Although 5 of 9 adjuvantly treated patients were long-term survivors compared to 2 of 17 treated surgically, a possible statistical advantage was obscured by the small numbers and unaltered rate of metastasis. Brady (5) published a report of six cases of ureteral TCC treated with RT. Of these, two were treated primarily with doses of 22 and 50 Gy with the second being locally
RT
i 5 f$
II
.60-
(p&07)
I,, S
50
:-1
.40-
No RT I____________________-.
s .20 1
OR 0
40
80
120
160
200
240
280
320
0
Months
Fig. 1. Kaplan-Meier curves for local control comparing therapy (n = 9) to no radiation (n = 17).
40
80
120
160
200
240
280
320
Months
radiation
Fig. 2. Kaplan-Meier survival curves comparing adjuvant diation (n = 9) to no adjuvant radiation (n = 17).
ra-
Transitional
cell carcinoma
controlled. Two others with local recurrences were locally controlled with 50 and 60 Gy. Of the two patients receiving adjuvant RT, one had a local recurrence after 40 Gy, the other being disease-free after receiving 50 Gy. Batata (2) compared adjuvant treatment to surgery alone. Five-year survivals were 1 of 6 and 1 of 5, respectively, however, the groups were selected with those receiving surgery only being Staged A or B and those treated adjuvantly Staged C or D. In addition, those treated postoperatively had gross residual disease and received mean doses of 33.75 Gy. Regional nodal failures to the ipsilateral pelvic and para-aortics were seen in all five patients who recurred in the postoperatively treated group. These were both in and out of the field of RT. Babaian (1) reported the M. D. Anderson Experience with true adjuvant RT given to eight patients. Only 1 of 8 had documented local recurrence, seen in conjunction with metastasis. Fields were tailored to the primary location with coverage of the para-aortics in renal pelvic or proximal ureteral lesions and the ipsilateral pelvic nodes for distal ureteral lesions. Adjuvant RT was given to I I Stage C or high grade cases and compared to 12 similar patients treated surgically by Brookland (6). A median dose of 50 Gy given with megavoltage energies was used. One LF in conjunction with metastasis compared to 5 of 11 were seen in the adjuvant and surgery only groups, respectively. Metastasis was unaffected by adjuvant radiation. Median survivals were 35 and 26 months in favor of the adjuvantly treated group. Others do not advocate RT. Rubenstein (11) reports on six patients: one treated preoperatively for residual disease, and two palliatively. Of the three treated postoperatively, one developed metastasis after starting treatment and the other two were lost to follow-up. Those treated palliatively had short-term relief of symptoms. He concluded the value of RT would be low because of the high risk of metastasis. The results of the current study correlate closely with
0 S. C. COZAD rl u/.
745
others (1, 6). Local recurrences are significantly reduced in this high stage population. In addition, grade is an independent prognostic factor that infers an approximate 70% risk of local recurrence which can be reduced to 1520% with the use of adjuvant RT. Decreased LF was accomplished with 6 of 9 receiving RT to tumor volumes that did not encompass the regional nodes. Since nodal recurrences were defined as LF’s, it seems unlikely that improved results could be achieved with fields large enough to treat the para-aortics and pelvic nodes. However, the high risk of recurrence in regional nodes suggest some patients could benefit from tumor nodal adjuvant RT. No dose response can be shown in this study because of the small numbers and narrow range of doses used. The one local recurrence followed a dose of 46 Gy. The 50% incidence of metastasis is unaffected by adjuvant RT and overshadows any possible survival benefit. This parallels Stage III and IV TCC of the bladder in which improved surgical techniques have reduced pelvic failures without increased survival because of distant recurrence. A recently reported trial of Cisplatin-based adjuvant treatment significantly increased disease-free progression and determinate survival in this population ( 13). Although this study has flaws and pertains to a different site, the similarities in clinical behavior and identical histology suggest a similar application in TCC of the ureter. Although it is risky to base patient management decisions on retrospective studies with their attendant patient selection biases, there are no prospective trials in this setting. We would, therefore, advocate ad.juvant RT in high stage or grade patients, or those with close or microscopic residual disease, with fields to encompass the primary tumor volume as well as regional nodes with a dose of 45 Gy followed by a boost to the primary site to approximately 50 Gy based upon the demonstrated decrease in local recurrence. Ideally, this would be combined with adjuvant systemic therapy in an effort to improve survival as well as local control.
REFERENCES 1. Babaian, R. J.; Johnson, D. E.; Chan, R. C. Combination nephroureterectomy and postoperative radiotherapy for in2.
3.
4.
5.
6.
filtrative ureteral carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 6:1229-1232;1980. Batata, M. A.; Whitmore, Jr., W. F.; Hilaris, B. S.; Tokita N.; Grab&d, H. Primary carcinoma of the ureter: A prognostic study. Cancer 35: 1626-1632;1975. Beahrs, 0. H.; Henson, D. E.; Hutler, R. V. P.; Myers, M. H.; American Joint Commission. Manual for staging of cancer, 3rd edition. Philadelphia, PA: J. B. Lippincott Company; 1988. Bloom, N. A.; Vidone, R. A.; Lytton, B. Primary carcinoma of the ureter: A report of 102 new cases. J. Ural. 103:590598;1970. Brady, L. W.; Gislason, G. J.; Faust, D. S.; Kazem, I.; Antoniades, J.; Davis, J. A. Radiation therapy. A valuable adjunct in the management of carcinoma of the ureter. JAMA 206:2871-2874;1968. Brookland, R. K.; Richter, M. P. The postoperative irra-
7. 8.
9. 10.
11.
12. 13.
diation of transitional cell carcinoma of the renal pelvis and ureter. J. Urol. 133:952-955;1985. Cox, D. R. Regression models and life tables. J. R. Stat. Sot. (B) 34:187-220;1972. Heney, N. M.; Necks, B. N.; Daly, J. J.; Blitzer, P. H.; Parkhurst, E. C. Prognostic factors in carcinoma of the ureter. J. Urol. 125:632-636;1981. Kaplan, E.; Meier, P. Nonparametric estimation from incomplete observations. J. Am. Stats. Ass. 53:457-481;1958. Mantel, N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50: 163- 170; 1966. Rubenstein, M. A.; Walz, B. J.; Bucy, J. G. Transitional cell carcinoma of the kidney: 25-year experience. J. Urol. 119:594-597;1978. Scott, W. W. A review of primary carcinoma of the ureter. J. Ural. 50:45-64;1943. Skinner, D. G.; Daniels, J. R.; Russell, C. A.; et al. J. Ural. 145:459-467;1991.
t .Xl
036%3016/92 $5.00 Copyright 0 IW? Pergamon Press Ltd.
24. PP. 743-145
??Brief Communication
ADJUVANT RADIOTHERAPY IN HIGH STAGE TRANSITIONAL CARCINOMA OF THE RENAL PELVIS AND URETER
CELL
SCOTTC.
COZAD, D.D.S., M.D.,’ STEPHEN R. SMALLEY, M.D., * MARK AUSTENFELD, M.D.,2 MARK NOBLE, M.D.,2 SCOTT JENNINGS, M.D.* AND RALPH REYMOND, M.D.3
‘Departmentof Radiation Oncology, ‘Department of Urology, University of Kansas Medical Center, Kansas City, KS; and 3Department of Radiation Oncology, St. Francis Hospital, Topeka, KS
This review was undertakento assess the influenceof adjuvantradiationtherapyon failure patternsand survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-fourpatients with transitionalcell carcinomaof the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 NO/+, MO disease and underwent curative resections (median follow-up 13.5 months, range 331 I). Local failure was defined as recurrence in the tumor bed, regional nodes, or ureteral stump. Time to recurrence and survival were calculated from the time of pathologic diagnosis. Variables associated with local failure, distant metastasis, and survival were analyzed using univariate and multivariate analysis. Seventeen received surgery only, nine received adjuvant radiation therapy (median dose 50 Gy). Local failure occurred in 9 of 17 without and 1 of 9 with adjuvant radiation therapy (p = 0.07). Actuarial S-year local control was 34% without and 88% with adjuvant radiation therapy. Cox step-wise regression confirmed adjuvant radiation therapy (p = 0.006) and grade (p = 0.006) as significantly associated with local failure. No patients with low grade lesions suffered local failure either with or without adjuvant radiation therapy. High grade lesions had an local failure rate of 15%with and 71%withoutadjuvantradiationtherapy.Metastaticdisease occurredin 4 of 9 and 8 of 17 with and without radiation therapy. No significant factors influencing distant failure were identified. Five-year actuarial survival was 44% with and 24% without adjuvant radiation therapy. The survival differences were not statistically significant on univariate or multivariate analysis. High staged transitional cell carcinoma of the renal pelvis or ureter has a substantial local failure risk after surgery alone. Adjuvant radiation therapy markedly reduces this risk but has no impact on distant disease which occurs in approximately 50%. Effective adjuvant therapy will require effective systemic therapy in addition to adjuvant radiation therapy. Transitional cell carcinoma, Renal pelvis, Ureter, Radiotherapy.
eluding type of surgical procedure and use of adjuvant RT or chemotherapy (CT) was collected (3). All were free of gross residual or metastatic disease following resection. Continuous course adjuvant RT was administered to nine with a median dose of 50 Gy (range 37.4 to 56.0). A variety of techniques were used including opposed AP/PA in four, AP/PA with a lateral field in one, posterior wedged pairs with a PA boost in one, PA and lateral in one, 360” rotational in one, and unknown fields in one. All were treated with megavoltage energies. In seven cases, treatment volume was known from port films or diagrams. Six of these had only the tumor bed (i.e., renal fossa or ureteral bed) included in the field. Local failure (LF) was defined as recurrence in the tumor bed, regional nodes, or in the ureteral stump. TCC of the bladder or contralateral renal pelvis and ureter were considered second primaries. The time to recurrence and survival were calculated from the time of histologic diagnosis. Median follow-up was 13 months (range 3-3 11).
INTRODUCl3ON The use of radiation in the treatment of transitional cell carcinoma (TCC) of the renal pelvis or ureter has proponents and detractors (1, 2, 4-6, 8, 11, 12). Many of these are based on poorly defined populations, and include recurrent or palliatively treated cases. This review will describe the outcome for high stage TCC resected for cure treated with or without adjuvant radiation therapy (RT). METHODS
AND MATERIALS
Twenty-six cases of TCC resected for cure and having American Joint Commission (AJC) pathologic Stage III or IV by virtue of positive nodes, were identified in the Medical Records at the University of Kansas Medical Center or the St. Francis Hospital in Topeka, Kansas. Information regarding patient age and gender, tumor histology, grade, size and nodal status, presence of close (~5 mm) or positive microscopic residual, and therapy in-
Accepted for publication
Reprint requests to: Dr. S. C. Cozad. 743
12 May 1992
744
I. J. Radiation Oncology 0 Biology 0 Physics
Survival and failure curves were generated for the variablesgender, age (80), grade (I and 2 vs 3 and 4), adjuvant RT, surgical procedure (nephroureterectomy with bladder cuff vs all others) and close or positive microscopic residual using the KaplanMeier actuarial method (9). The significance of individual variables were tested using the generalized Savage (MantleCox) test (10). Multivariate analysis with the same variables was performed using the Cox step-wise method (7).
Table 1. Probability of local recurrence by grade and use of adjuvant RT in high stage patients Local recurrence
Adjuvant
RT
Grade
Yes No Yes No
o/4 o/4 115 9/13
Low Low High Hiah
three cases treated adjuvantly failed compared to both not receiving adjuvant RT.
RESULTS
The median ages of the adjuvant RT and surgery groups were 7 1 and 68, respectively. Six of nine adjuvant patients were male versus 12 of 17 treated surgically. Five and 13 high grade lesions were seen in the two groups. The adjuvant RT group had three cases in which there were close margins or microscopic residual disease. Two such cases were found in the surgery only group. Six patients received less than a total nephroureterectomy in the surgery group compared to one in the adjuvant RT. None of these patient, tumor, or treatment parameters was significantly different between the two groups. Local recurrence Local recurrence occurred in 10 cases and was always a component of initial failure. The absolute number of local recurrences were 9 of 17 and 1 of 9 for the surgery only and adjuvantly treated groups. Actuarial rates at 5 years are 34% and 88%, respectively (Fig. 1). The difference is of borderline significance by the Savage (Mantel Cox) test with a value ofp = 0.07. Controlling for the variables age, sex, adjuvant RT, surgical procedure, grade, and closer microscopic residual disease, only the use of adjuvant RT (p = 0.006) and grade (p = 0.006) were significant factors influencing local recurrence. Table 1 shows the probability of local recurrence by grade and use of adjuvant RT in these high stage patients. The presence of close margins or microscopic residual disease did not effect local control, however, none of the
Yes
Volume 24, Number 4, 1992
Metastasis Overall, 14 of 26 developed metastasis, 12 as a component of initial failure. In the group receiving adjuvant RT, 4 of 9 developed metastasis compared to 10 of 17 treated surgically. There were no significant tumor or treatment parameters effecting the development of metastasis. Survival Twenty of 26 patients have died. The absolute and 5year actuarial rates are 5 of 9 and 44% for those treated adjuvantly compared to 2 of 17 and 24% for those treated surgically (Fig. 2). This was not significant (p = 0.23). Controlling for age, sex, surgical procedure, and grade, adjuvant therapy continued to be without significance (p = 0.14) and no other variables became significant. DISCUSSION
This review contains 26 stage T3 cases of TCC of the renal pelvis or ureter. Only nine were treated with adjuvant RT. However, inspite of the small number of patients, local control was statistically significantly improved from 34% to 88%. Although 5 of 9 adjuvantly treated patients were long-term survivors compared to 2 of 17 treated surgically, a possible statistical advantage was obscured by the small numbers and unaltered rate of metastasis. Brady (5) published a report of six cases of ureteral TCC treated with RT. Of these, two were treated primarily with doses of 22 and 50 Gy with the second being locally
RT
i 5 f$
II
.60-
(p&07)
I,, S
50
:-1
.40-
No RT I____________________-.
s .20 1
OR 0
40
80
120
160
200
240
280
320
0
Months
Fig. 1. Kaplan-Meier curves for local control comparing therapy (n = 9) to no radiation (n = 17).
40
80
120
160
200
240
280
320
Months
radiation
Fig. 2. Kaplan-Meier survival curves comparing adjuvant diation (n = 9) to no adjuvant radiation (n = 17).
ra-
Transitional
cell carcinoma
controlled. Two others with local recurrences were locally controlled with 50 and 60 Gy. Of the two patients receiving adjuvant RT, one had a local recurrence after 40 Gy, the other being disease-free after receiving 50 Gy. Batata (2) compared adjuvant treatment to surgery alone. Five-year survivals were 1 of 6 and 1 of 5, respectively, however, the groups were selected with those receiving surgery only being Staged A or B and those treated adjuvantly Staged C or D. In addition, those treated postoperatively had gross residual disease and received mean doses of 33.75 Gy. Regional nodal failures to the ipsilateral pelvic and para-aortics were seen in all five patients who recurred in the postoperatively treated group. These were both in and out of the field of RT. Babaian (1) reported the M. D. Anderson Experience with true adjuvant RT given to eight patients. Only 1 of 8 had documented local recurrence, seen in conjunction with metastasis. Fields were tailored to the primary location with coverage of the para-aortics in renal pelvic or proximal ureteral lesions and the ipsilateral pelvic nodes for distal ureteral lesions. Adjuvant RT was given to I I Stage C or high grade cases and compared to 12 similar patients treated surgically by Brookland (6). A median dose of 50 Gy given with megavoltage energies was used. One LF in conjunction with metastasis compared to 5 of 11 were seen in the adjuvant and surgery only groups, respectively. Metastasis was unaffected by adjuvant radiation. Median survivals were 35 and 26 months in favor of the adjuvantly treated group. Others do not advocate RT. Rubenstein (11) reports on six patients: one treated preoperatively for residual disease, and two palliatively. Of the three treated postoperatively, one developed metastasis after starting treatment and the other two were lost to follow-up. Those treated palliatively had short-term relief of symptoms. He concluded the value of RT would be low because of the high risk of metastasis. The results of the current study correlate closely with
0 S. C. COZAD rl u/.
745
others (1, 6). Local recurrences are significantly reduced in this high stage population. In addition, grade is an independent prognostic factor that infers an approximate 70% risk of local recurrence which can be reduced to 1520% with the use of adjuvant RT. Decreased LF was accomplished with 6 of 9 receiving RT to tumor volumes that did not encompass the regional nodes. Since nodal recurrences were defined as LF’s, it seems unlikely that improved results could be achieved with fields large enough to treat the para-aortics and pelvic nodes. However, the high risk of recurrence in regional nodes suggest some patients could benefit from tumor nodal adjuvant RT. No dose response can be shown in this study because of the small numbers and narrow range of doses used. The one local recurrence followed a dose of 46 Gy. The 50% incidence of metastasis is unaffected by adjuvant RT and overshadows any possible survival benefit. This parallels Stage III and IV TCC of the bladder in which improved surgical techniques have reduced pelvic failures without increased survival because of distant recurrence. A recently reported trial of Cisplatin-based adjuvant treatment significantly increased disease-free progression and determinate survival in this population ( 13). Although this study has flaws and pertains to a different site, the similarities in clinical behavior and identical histology suggest a similar application in TCC of the ureter. Although it is risky to base patient management decisions on retrospective studies with their attendant patient selection biases, there are no prospective trials in this setting. We would, therefore, advocate ad.juvant RT in high stage or grade patients, or those with close or microscopic residual disease, with fields to encompass the primary tumor volume as well as regional nodes with a dose of 45 Gy followed by a boost to the primary site to approximately 50 Gy based upon the demonstrated decrease in local recurrence. Ideally, this would be combined with adjuvant systemic therapy in an effort to improve survival as well as local control.
REFERENCES 1. Babaian, R. J.; Johnson, D. E.; Chan, R. C. Combination nephroureterectomy and postoperative radiotherapy for in2.
3.
4.
5.
6.
filtrative ureteral carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 6:1229-1232;1980. Batata, M. A.; Whitmore, Jr., W. F.; Hilaris, B. S.; Tokita N.; Grab&d, H. Primary carcinoma of the ureter: A prognostic study. Cancer 35: 1626-1632;1975. Beahrs, 0. H.; Henson, D. E.; Hutler, R. V. P.; Myers, M. H.; American Joint Commission. Manual for staging of cancer, 3rd edition. Philadelphia, PA: J. B. Lippincott Company; 1988. Bloom, N. A.; Vidone, R. A.; Lytton, B. Primary carcinoma of the ureter: A report of 102 new cases. J. Ural. 103:590598;1970. Brady, L. W.; Gislason, G. J.; Faust, D. S.; Kazem, I.; Antoniades, J.; Davis, J. A. Radiation therapy. A valuable adjunct in the management of carcinoma of the ureter. JAMA 206:2871-2874;1968. Brookland, R. K.; Richter, M. P. The postoperative irra-
7. 8.
9. 10.
11.
12. 13.
diation of transitional cell carcinoma of the renal pelvis and ureter. J. Urol. 133:952-955;1985. Cox, D. R. Regression models and life tables. J. R. Stat. Sot. (B) 34:187-220;1972. Heney, N. M.; Necks, B. N.; Daly, J. J.; Blitzer, P. H.; Parkhurst, E. C. Prognostic factors in carcinoma of the ureter. J. Urol. 125:632-636;1981. Kaplan, E.; Meier, P. Nonparametric estimation from incomplete observations. J. Am. Stats. Ass. 53:457-481;1958. Mantel, N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50: 163- 170; 1966. Rubenstein, M. A.; Walz, B. J.; Bucy, J. G. Transitional cell carcinoma of the kidney: 25-year experience. J. Urol. 119:594-597;1978. Scott, W. W. A review of primary carcinoma of the ureter. J. Ural. 50:45-64;1943. Skinner, D. G.; Daniels, J. R.; Russell, C. A.; et al. J. Ural. 145:459-467;1991.
