Most superficial tumors are likely to be well differentiated, and those tumors that are infiltrative are likely to be poorly differentiated. The incidence of synchronous or metachronous contralateral upper tract cancers ranges from 2% to 4%; the incidence of subsequent bladder cancer after prior upper tract transitional cell cancer ranges from 30% to 50%.When involvement of the upper tract is diffuse (involving both the renal pelvis and ureter), the likelihood of subsequent development of bladder cancer increases to 75%.

see guidelines from the NCCN below which recommend surgery followed by chemotherapy (T3) or chemoradiation for T4 or node + cases

Adjuvant radiotherapy in high stage transitional cell carcinoma of the renal pelvis and ureter.

Cozad SC, Smalley SR, Austenfeld M, Noble M, Jennings S, Reymond R

Department of Radiation Oncology, University of Kansas Medical Center, Kansas City.

This review was undertaken to assess the influence of adjuvant radiation therapy on failure patterns and survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-four patients with transitional cell carcinoma of the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 N0/+, M0 disease and underwent curative resections (median follow-up 13.5 months, range 3-311). 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 5-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% without adjuvant radiation therapy. Metastatic disease occurred in 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.

The postoperative irradiation of transitional cell carcinoma of the renal pelvis and ureter.

Brookland RK, Richter MP.   J Urol 1985 Jun;133(6):952-5

The role of adjuvant irradiation in the treatment of transitional cell carcinoma of the renal pelvis and ureter was reviewed. Between June 1966 and March 1981, 41 patients underwent curative resections. A poor risk group was identified, with 23 patients demonstrating disease greater than grade 2 or stage B. Postoperative irradiation was administered to 11 of 23 patients. Median patient followup was 40 months. Two-thirds of all failures occurred within the first 12 months and no failure was seen beyond 35 months. Patients with poor prognostic features had a 60 per cent failure rate compared to 11.8 per cent of the patients with good risk factors (p equals 0.023). The median survival of the 2 groups was 28 and 99 months, respectively (p less than 0.001). Outcome of the poor risk patients was analyzed whether or not the patient received postoperative irradiation. None of the irradiated patients failed with local disease only, while there was 1 patient with local and distant recurrence. In contrast, the nonirradiated group had 5 local failures and twice the number of failures over-all. Median survival of the irradiated and nonirradiated patients was 35 and 26 months, respectively. The number of patients treated is too small to permit valid statistical conclusions and indicates the need for a multi-institutional study to determine if these suggestive findings of improved local control will be corroborated and translate into an improved survival rate.

Postoperative radiation therapy in 26 patients with invasive transitional cell carcinoma of the upper urinary tract: no impact on survival?

Maulard-Durdux C, J Urol 1996 Jan;155(1):115-7

Department of Radiation Therapy, St. Louis Hospital, Paris, France.

Between February 1980 and October 1993, 18 men and 8 women (mean age 65 +/- 9 years, standard deviation) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 (58%). Tumor grade was 2 in 10 patients, 3 in 15 and unknown in 1. One patient had epidermoid metaplasia of urothelial cancer and 9 had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy. to the tumor bed (23) and/or regional nodes (18). RESULTS: After a mean followup of 45 months 13 patients (50%) were alive and 11 were disease-free at analysis. Local tumor relapse, nodal recurrence and metastasis were noted in 1, 4 (15%) and 14 (54%) patients, respectively. All patients with nodal recurrence had metastasis. A secondary location was noted frequently (6 bladder, 1 contralateral renal pelvis and 1 urethral tumors). Overall 5-year survival rate and 5-year survival rate with no evidence of disease were 49% and 30%, respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (p = 0.07), 49% for node-negative versus 15% for node-positive cancer (p = 0.04), and 90% for grade 2 and 0% for grade 3 tumors (p < 0.01). CONCLUSIONS: In our trial using a radio-surgical approach, local control of disease and survival rates were similar to those reported previously in surgical series. Prophylactic postoperative radiation therapy is not recommended except in prospective randomized studies.

Advanced transitional cell carcinoma of the upper urinary tract: patterns of failure, survival and impact of postoperative adjuvant radiotherapy.

Hall MC, J Urol 1998 Sep;160(3 Pt 1):703-6

Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA.

PURPOSE: We review the outcome of patients with advanced stage III or IV transitional cell carcinoma of the upper urinary tract and the impact of postoperative radiotherapy. MATERIALS AND METHODS: We identified 74 patients who were treated surgically with curative intent for stage III (49) or IV (25) transitional cell carcinoma of the upper urinary tract. Median followup was 21 months (range 1 to 236) for all patients and 60 months (range 29 to 172) for those alive at last contact. A median dose of 40 Gy. adjuvant radiotherapy was delivered to the tumor bed and regional nodes of 15 patients (30%) with stage III and 13 (52%) with stage IV disease. RESULTS: The actuarial 5-year overall and disease specific survival for patients with stage III disease was 28 and 40%, respectively. Median disease specific survival was 37 months. Median overall and disease specific survival for patients with stage IV disease was 7 months. Isolated local recurrence was identified in 5 of 49 patients with stage III and only 1 of 25 with stage IV disease. The 5-year actuarial disease specific survival rate in patients with stage III disease whether or not they were treated with postoperative radiotherapy was 45 versus 40%, respectively. For patients with stage IV disease median survival was 7 and 9 months for those who were and those who were not treated with postoperative radiotherapy, respectively. CONCLUSIONS: Patients with stages III and IV transitional cell carcinoma of the upper urinary tract have a high risk of disease relapse and cancer mortality. The major clinical feature is distant failure with isolated local relapse uncommon following initial aggressive surgical therapy. There is no survival benefit with postoperative adjuvant radiotherapy. More effective systemic adjuvant therapy is necessary to improve the outcome of these patients.