Radiation Oncology/Ureter

Renal Pelvis and Ureter

Prognostic factors
most important prognostic factors are stage at presentation and histological grade location of tumor in locally advanced disease may be of prognostic significance
 * 5 year OS
 * stage I and II >60%
 * stage III ~33%
 * stage IV <15%
 * long-term prognosis adversely related to
 * number lesions multifocal disease
 * DNA pattern (e.e heteroploid)
 * hypermethylation of promoter region

Staging
AJCC 7th Edition (2009) Primary Tumor:
 * Ta - papillary non-invasive carcinoma
 * Tis - carcinoma in situ
 * T1 - invades subepithelial connective tissue
 * T2 - invades muscularis
 * T3 (Renal pelvis) - invades into peripelvic fat or renal parenchyma
 * T3 (Ureter) - invades into periureteric fat
 * T4 - invades adjacent organs or through the kidney into perinephric fat

Regional Lymph Nodes:
 * Regional lymph nodes (for renal pelvis) - renal hilum, paracaval, aortic, retroperitoneal
 * Regional lymph nodes (for ureter) - renal hilum, iliac, paracaval, periureteral, pelvic


 * N1 - single lymph node, 2 cm or less in greatest dimension
 * N2 - single lymph node, 2-5 cm; or multiple lymph nodes, none > 5 cm
 * N3 - node > 5 cm

Distant Metastases:
 * M0 - no
 * M1 - yes

Stage Grouping:
 * I - T1 N0
 * II - T2 N0
 * III - T3 N0
 * IV - T4, N+, M1

AJCC 6th Edition No changes compared to 7th edition

General Principles of treatment

 * surgery only curative treatment and should be considered
 * Adjuvant XRT used with locally advanced (stage III or above) or grade 3-4 TCC
 * Adjuvant chemo effect unknown. Because of high risk of distant mets, may be considered after complete resection
 * If unresectable (or medically inoperable), treat with definitive chemoXRT.

Surgery

 * use nephron-sparing surgery or partial ureterectomy for single site, stage I and low grade lesions <1.5 cm
 * standard technique is nephroureterectomy with removal of the bladder cuff

Radiation

 * adjuvant XRT shown to improve locoregional control and disease-free survival but effect on OS not consistently demonstrated (small retrospective series, Cozad 1995) (NO prospective randomized trials)

Studies:
 * U.Kansas 1992 PMID 1429099 -- "Adjuvant radiotherapy in high stage transitional cell carcinoma of the renal pelvis and ureter." (Cozad SC, Int J Radiat Oncol Biol Phys. 1992;24(4):743-5.)
 * Retrospective. 26 pts w/ TCC of renal pelvis or ureter, Stage III-IV (M0), treated w/ curative attempt surgery. Adjuvant RT given to 9 pts, median 50 Gy. Treatment volume was the tumor bed only in 6 pts
 * Median f/u 13 mo. LR in 10 pts; 9 of 17 (no RT group), 1 of 9 (RT group). 5-yr LC 34% (no RT) vs 88% (RT). On multivariate analysis, only RT was significant for influencing LR. Metastasis: DM in 14 pts (12 as a component of first failure); 10 of 17 (no RT), 4 of 9 (RT). Survival: 20 of 26 have died; 5-yr OS 24% (no RT), 44% (RT). RT did not have a significant effect on survival.
 * Conclusion: RT decreases the rate of local failure. Advocate adjuvant RT for pts with high stage or high grade tumors or those with close or positive margins. Ideally, this should be combined with systemic therapy.

Chemo

 * platinum-based given concurrently with XRT for localled advanced (T3-T4, N+) TCC upper urinary tract
 * in adjuvant setting reduces risk of distant mets upper urinary tract (bamias 2004, kwak 2006)
 * adjuvant chemoXRT more effective than adjuvant XRT alone based on retrospective study from mass gen for T3,T4,N+ (Czito, et al, 2004)

Studies:
 * Mass General, 2004 (1970-1997) PMID 15371822 -- "Adjuvant radiotherapy with and without concurrent chemotherapy for locally advanced transitional cell carcinoma of the renal pelvis and ureter." (Czito B, J Urol. 2004 Oct;172(4 Pt 1):1271-5.)
 * Retrospective. 31 pts (renal pelvis-13, ureter-15, both-3) treated with RT following curative resection. Most (28 of 31) had T3/4 or N+ disease. Median RT dose 46.9 Gy. 9 pts treated with chemotherapy (MTX,cisplatin,vinblastine x 2-4 cycles, followed by concurrent cisplatin with RT).
 * Median f/u 2.6 yrs. MS 2.4 yrs. 52% with relapse; 29% with DM alone; 23% had LRF (with DM developing in all but 1 pt). 5-yr OS 39%, DSS 52%, LRC 62%, metastasis-free survival 48%. On univariate analysis, concurrent chemotherapy improved OS (27% vs 67%) and DSS (41% vs 76%).
 * Conclusion: suggests that the addition of concurrent chemotherapy to radiotherapy improves outcomes for resected locally advanced disease