Radiation Therapy for Ureteral Metastases from Breast Carcinoma

GENE KOPELSON, MD,' JOHN E. MUNZENRIDER, MD,' RITA M. KELLEY, MD,t AND WILLIAM U. SHIPLEY, MD*

Seven breast cancer patients received supervoltage radiation therapy in the Department of Radiation Medicine, Massachusetts General Hospital from 1970- 1978 for ureteral-periureteral metastases. Urinary symptoms (flank pain, urgency, hematuria) disappeared completely and permanently for four of five patients; abnormal pyelograms returned completely to normal for three of three; and abnormal renal function tests for two of two. Six of seven patients survived at least one year after irradiation. In- dications for irradiation, dose, and techniques are discussed.

Cancer 47:1976-1979, 1981.

R E T E R A L M E T A S T ~ S E S from breast carcinoma U were first reported by Rathbun in 1929,' and approximately 8% of autopsied breast cancer patients have ureteral or periureteral metastases.'..' The largest clinical series was 24 patients reported from Memorial Hospital by Grabstadt and Kaufman-'; five of their pa- tients were irradiated primarily, one survived 17 months. Subsequent reports from the same institution describe irradiation of six additional patients."." Surgi- cal management has consisted of stent, ureteroly- sis, ureterostomy, nephrostomy, or nephroureterec- t ~ m y . ~ , ' . ~ . ~ Hormonal manipulation in patients with estrogen receptor positive ureteral metastasis has been advocated.x.9 The use of chemotherapy has also been described.-'.'sX Because reports documenting the ef- ficacy of radiation therapy in this potential life-threat- ening condition are sparse, we report our experience with supervoltage radiotherapy in seven patients with ureteral obstruction from metastatic breast cancer.

Materials and Methods

From January 1970 to September 1978, seven women received supervoltage radiation therapy for ureteral and/or periureteral metastases from breast carcinoma in the Department of Radiation Medicine, Massachu-

From the "Department of Radiation Medicine and tDivision of Medical Oncology, Massachusetts General Hospital, Boston, Massa- chusetts.

Address for reprints: Gene Kopelson, MD, Department of Radiation Medicine. Massachusetts General Hospital, Boston, M A 02114.

The authors thank Mindy Printz-Kopelson for her help in the preparation of this rnanuscnpt.

Accepted for publication May 5 . 1980.

setts General Hospital. The time interval from initial management of the breast carcinoma to diagnosis of ureteral metastasis ranged from 17 months to 15 years, 4 months with a median of five years. Four patients had ureteral metastasis as their initial site of failure: five had had hormonal manipulation and/or chemo- therapy for other metastatic disease or adjuvantly be- fore the recognition of the ureteral metastasis. Six of the seven had histologic proof of ureteral metastasis.

The patient population and their clinical course are presented in Table 1 . The one patient (Patient 5) with- out preirradiation pyelogram had tumor obstruction at the ureteropelvic junction at cystoscopy. Only three (Patients 1, 4, 7) had palliative surgical diversionary procedures before irradiation. Patients 4 and 7 were referred for irradiation when renal function tests re- mained elevated after surgery. Patient 1 was treated because of rising B U N and creatinine levels after stent plus ureteral reimplantation.

Patients were treated with ""Co gamma rays, or with 2, 10, or 25 MV x-rays. Parallel-opposed anterior- posterior fields were used in each patient, usually covering the ipsilateral uretedperiureteral tissues (Fig. 1 AB) for unilateral disease; bilateral ureters for bi- lateral disease; or treatment to the distal ureter and pelvis for ureterovesical junction metastases (Fig. 2AB). Individual doses appear in Table 1. Patients 2 and 3 were placed on adjuvant combination chemotherapy after irradiation.

Response

Symptoms of flank pain, urgency, and/or hematuria disappeared completely and permanently for four of

0008-543X/81/0415/1976 $0.75 C American Cancer Society

1976

No. 8 IRRADIATION FOR URETERAL METASTASES ' Kopelsori et d. 1977

FIG. I . A 72 year-old woman (patient 1 ) with elevated BUN and creatinine levels 15 years after mastectomy, whose initial pyelogram showed hydronephrosis of her right double collecting system. At exploration, a long sleeve of biopsy-proven metastatic breast carcinoma en- veloped both right ureters. Ureteral stent and ureteroureterostomy were performed. Rising BUN and creatinine levels postoperatively prompted referral for irradiation. She received 4000 rads in 16 fractions on a 25 MeV linear accelerator via these anterior-posterior portals (Fig. 1A) encompassing the ipsilateral ureters and ureterovesical junction. One year later, her pyelogram was normal (Fig. IB). Time-course changes in her renal function are in Figure 3.

five patients (3/3 flank pain, 3/4 urgency/dysuria, 1/1 hematuria). Pyelograms returned completely to normal for three patients in whom pre- and postirradiation studies were obtained (Fig. l B , 2B), although reob- struction due to biopsy-proven local failure at 28 months postirradiation occurred in one (Table 1). Ab- normal preirradiation renal function tests in two pa- tients returned to normal postirradiation (Fig. 3). Thus, symptoms, creatinine level, and/or pyelograms re- turned completely to normal for the remainder of the patient's life in six of seven patients.

Six of seven patients survived at least one year after completion of irradiation.

Discussion

Palliation achieved with irradiation, i.e., sympto- matic relief, improved renal function, and relief of ob- struction on pyelography, is similar to that reported

previously.4-" The volume irradiated should include the ipsilateral ureter for unilateral disease and both ureters and pelvis in patients with bilateral disease. The one patient with recurrent obstruction after irradi- ation received the highest dose (250 rads x 19, time dose fractionation 89: Patient 2) and also has had the longest follow-up. Thus, because of the possibility that more in-field failures will be observed with longer follow-up, we recommend doses higher than the 3600 rads recommended by Memorial Hospital"." and would treat such patients to 4500 rads at 180-200 rads per day to the ureter(s) with subsequent small-field boost of about 1000 rads to the area of demonstrable ob- struction. In patients with advanced metastatic disease involving other sites, shorter irradiation courses would seem more justifiable, however.

Computed body tomography and/or ultrasound of ureteral metastases can provide additional informa- tion about tumor extent"' beyond that provided by routine uroradiologic studies, and thus may better de-

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FIG. 2. A 50 year-old women (patient 2) with right hydronephrosis 18 months after initial treatment for a T,N,,, primary. Exploration revealed biopsy-proven metastasis at the distal ureter and uretrovesicaljunction. She received 4000rads in 16fractionsviaanterior-posterior 14 x IS cm fields with " T o to the entire bladder. both distal ureters, and ureterovesical junctions with subsequent boost via 9 x 10 cm portals (Fig. 2A) to the area marked by clips (clips not seen here because her fields were redrawn onto her initial preirradiation pyelogram: her simulatorfilms were only of the lower pelvis). Ten months later. her pyelograni was normal (Fig. 28) .

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lineate the complete extent of tumor and aid in de- signing subsequent irradiation portals.

It is not known whether combined surgical decom- pression and irradiation might be better than either modality alone. Individualization of treatment of such patients seems justifiable. Patients with isolated ure- teral metastases should probably be treated with an aggressive combination of surgery, irradiation, and chemo/hormonal therapy in a vigorous attempt at long- term control. The addition of irradiation in a patient already relieved by surgical means in the face of limited life-span may not be indicated. However, patients 1,4, and 5 had distant metastases present before diagnosis of their ureteral metastasis; two are alive at 22 and 19 months, respectively, and one died at 20 months after completion of irradiation (Table 1). Thus, irradi- <

FIG. 3 . Time-course changes in B U N and creaiinine levels for pa- tient l , whose radiographic changes after irradiation are seen in Figure 1. Although renal function transiently returned toward normal after stent and ureteroureterostomy. levels rose again before irradi- ation. However. B U N and creatinine levels fell dramatically during course of irradiation and remained normal as of last follow-up.

No. 8 I R R A D I A T I O N FOR URETERAL ME I'ASTASES . Kopelsoii ef ( 1 1 . I979

TABLE 1 . Clinical Course of Irradiated Patients

Laboratory studies belore Rndiiition therapy technique Follow-up after I r r ;d imon irradiation

Surgery before C l e a t l ~ Kad, Urinary' K a d w CI-eati- I i i $ l

A;:e irradiation Radiographic B U N nine Modality frdction5 T D F ,ymptoms graphic B U N nine Survival stdtu,

Patient I 7: yr. Stent t Urr tero Ureteroatomy

Piitient 2 ?O yr None

Patient 3 47 yr None

Patient 4 S X yr. Percutaneous Nephrostomiea

Patient 5 31 )I- None

Patient 6 44 yr None

Patient 7 h? yr. Stent.

Unilateral ureteral 33 obstruction

Unilateral ureteral W N L ohstruction

Unilateral ureteral W N L obstruction

Bilateral ureteral i obstruction

- W N L

Bilateral ureteral -

obstruction

Unilateral ureteral - obstruction

2.9

W N L

W N L

i

1.8

25X 3060117

IOX 3000/1?

14 W N L

89 Gone" W N L "

48 i WNL

68 Gone -

62 Gone -

40 Gone -

26 Gone -

WN L

WNL.

WNL.

WNL.

WNI.

-

-

W N L

W N L

W N L

-

WNL.

-

W N I .

I yr. I0 imo

3 y i . 3 mo

I yr. 3 mo.

I y r . 7 mo.

I yr. 8 mo

I yr. 4 mil.

I mo.

A . 1.C

A . 1.F

1). I c

A . I C

I). 1.c

D. L C

I). 1 c

A ~ alive: D ~ dead. LC = local control o f ureteral metastases: LF = Inca1 failure:

' Flank pain. urgency. dysuria. and/or hematuria. 7 Patient had cramps. abdominal pain. and fullness due to pelvic-periureferal mas%.

T D F = time-do~e-Fractionation.

hut no specific iirologic 3ymptoms.

ation should generally be considered in this situation because of the long history that patients with breast carcinoma metastatic to the ureter can exhibit.H

REFERENCES

I . Rathbun NP. Scirrhous carcinoma of the ureter: late metas- tasis from carcinoma of the breast. J Urol 1929; 21:507-509.

2 . Abrams HL. Spiro R, Goldstein N. Metastases in carcinoma. c~</!rcc,r 19x1: 3:74-85.

3 . Geller SE, Lin LS. Ureteral obstruction from metastatic breast carcinoma. Arc.11 Prrrhol 1975: 99:476-479.

4. Grabstald H, Kaufman R. Hydronephrosis secondary to ure- teral obstruction by metastatic breast cancer. J Urol 1969: 102: 569-573.

i Laboratory values were abnormal before nephrostomies. hut none were recorded after

8 After completion o f irradiation: status as of (180. " Later symptomatic recurrence at bilateral ureteiopelvic junctwn\ with ?tent plxement

nephrmtomies but before irradiation.

(ree textl.

5 . Chu FCH. Radiotherapy for Symptomatic Relief. I ~ J : Stoll BA, ed., Brrtrst CNIICCI. Mtrtitr,gc,rtJetrt, Chicago: Year Book Medical Publishers. 1977: 129- 135.

6. Chu FCH. Solis M. Grabstald H . Radiation therapy for ureteral metastases for breast cancer. Clit7 Err// 1977: 7: 105- 108.

7. Case Records of the MGH (Case 44-1975). N Etrgl J , \ I d 1975; 293: 1034- 1038.

8. Feun LG. Drelichman A. Singhakowinta A, Vaitkevicius VK. Ureteral obstruction secondary to metastatic breast carcinoma. C.trric.cr 1979: 44: 1164- 1171.

9 . Giuliano A E . Sparks FC. Morton DL. Breast cancer presenting as I-enal colic. Aui J Sro'g 1978: 135:842-845.

10. Ambos MA. Bosniak M A . Megibow AJ. Raghavendra B. Ureteral involvement by metastatic disease. Urol Kircliol. 1979; 1:105-112.