# Radiation Oncology/Urethra

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Urethra - includes urothelial (transitional cell) carcinoma of the prostate

## Epidemiology

* Male urethral CA occurs in 40's
* Female urethral CA occurs in pts >50.
* F>M 4:1

## Anatomy

Male Urethra
* Runs from bladder neck to glans penis.
* Anterior Urethra includes glandular, penile, and bulbous urethra.
* Posterior Urethra includes membranous and prostatic urethra.
Female Urethra
* Mostly buried in anterior wall of vagina.
* Proximal Urethra includes proximal 2/3 of urethra.
* Distal Urethra includes distal 1/3 of urethra.
Nodal drainage
* Anterior urethra drains to superficial and deep inguinal nodes.
* Posterior urethra drains to pelvic nodes (ext iliac, hypogastric, obturator).
Sites of disease
* Most common site of disease in males is bulbomembranous urethra.
* Most common site of disease in females is near meatus.

## Staging
### AJCC Staging (7th edition, 2009)

T-stage (Male and Female)
* Ta - non-invasive papillary, polypoid, or verrucous carcinoma
* Tis - carcinoma in situ
* T1 - invades subepithelial connective tissue
* T2 - invades any of the following: corpus spongiosum, prostate, periurethral muscle
* T3 - invades any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder neck
* T4 - invades other adjacent organs
T-stage - Urothelial (transitional cell) carcinoma of the prostate:
* Tis (pu) - in situ, involvement of the prostatic urethra
* Tis (Pd) - in situ, involvement of the prostatic ducts
* T1 - invades subepithelial connective tissue
* T2 - invades any of the following: prostatic stroma, corpus spongiosum, periurethral muscle
* T3 - invades any of the following: corpus cavernosum, beyond prostatic capsule, bladder neck (extraprostatic extension)
* T4 - invades other adjacent organs (invasion of the bladder)
N-stage:
* N0 - none
* N1 - single lymph node 2 cm or less
* N2 - single lymph node > 2 cm, or multiple nodes
M-stage:
* M0 - no
* M1 - yes
Overall stage:
* I - T1 N0
* II - T2 N0
* III - T3 or N1
* IV - T4 or N2 or M1

### Prempree Staging

for carcinoma of female urethra
* Prempree Stage I - distal 1/2 urethra
* Prempree Stage II - entire urethra, peri-urethral tissues; no vulvar or bladder neck involvement
* Prempree Stage IIIA - urethra + vulva
* Prempree Stage IIIB - vaginal mucosa
* Prempree Stage IIIC - urethra + bladder neck
* Prempree Stage IVA - parametrium or paracolpium
* Prempree Stage IVB - +nodes or distant mets

## Treatment of Female Urethral Cancer

* Small lesions (<4cm) can be treated w/ brachytherapy alone.
* Larger lesions are treated with combination of external beam radiation and brachytherapy.

### Definitive Radiation

* Mallinckrodt (1959-95) PMID 9635699 -- Grigsby PW. "Carcinoma of the urethra in women," Int J Radiat Oncol Biol Phys. 1998 Jun 1;41(3):535-41.
** 44 women w/ carcinoma of the urethra. T1-T4. Median FU time 8.25 yrs. Tx w/ surgery in 7, xrt in 25, surg + xrt in 12.
** 5yr OS 42%, 5yr CSS 40%
** Tumor size (>4cm) and histology (adenoCA) were poor prognostic factors on multi-variate analysis. Tumor location not prognostic.
* Princess Margaret (1961-90) PMID 10869752 -- Milosevic MF. "Urethral carcinoma in women: results of treatment with primary radiotherapy," Radiother Oncol. 2000 Jul;56(1):29-35.
** 34 women w/ primary urethral CA (stage I-IV) tx'd w/ xrt; xrt fields included to tumor only, to tumor + nodes, and w/ interstitial brachytherapy.
** 7yr OS 41%, 7yr CSS 45%
** Benefit of brachytherapy seen most in pts w/ bulky tumor. Large tumor size only independent predictor of dz recurrence.
* M.D. Anderson (1955-89) PMID 8490839 -- Garden AS. "Primary carcinoma of the female urethra. Results of radiation therapy." Cancer. 1993 May 15;71(10):3102-8.
** 97 pts w/ primary urethral CA tx'd w/ xrt
** 5yr OS 41%, 10yr OS 31%, 64% local control at 5 yrs w/ xrt alone.
** 49% of those whose dz was controlled locally had symptomatic complications (urethral stenosis, fistula, necrosis)

## Treatment of Male Urethral Cancer

* Standard treatment option for T1-T3 disease remains surgical (amputation or partial amputation).
* Distal lesions have been treated curatively with definitive xrt w/ doses >70 Gy.

### Surgery

* MSKCC (1958-96) PMID 10367840 -- Dalbagni G et al. "Male urethral carcinoma: analysis of treatment outcome." Urology. 1999 Jun;53(6):1126-32.
** 46 pts w/ primary CA of bulbar/anterior urethra. 78% w/ locally advanced dz. External beam xrt used as part of salvage for locally recurrent.
** 5 yr OS 42%
* M.D. Anderson (1979-90) PMID 8154072 -- Dinney CP et al. "Therapy and prognosis for male anterior urethral carcinoma: an update." Urology. 1994 Apr;43(4):506-14.
** 23 pts tx'd w/ primary urethral CA
** Tumors of fossa navicularis and penile urethra could be tx'd w/ distal urethrectomy/partial penectomy.
** Tumors of bulbomembranous urethra best tx'd w/ en bloc excision of penis, scrotum, prostate, bladder.
* St. George's Hospital, UK PMID 17488307 -- Smith Y et al. "Penile-preserving surgery for male distal urethral carcinoma." BJU Int. 2007 May 4
** 18 consecutive pts w/ distal urethral CA tx'd w/ penile-preserving surgery; median FU 26 mo's
** No local recurrences, but 4 w/ regional nodal dz progressed.

### Chemoradiation

* Lahey Clinic PMID 8944514 -- Oberfield RA et al. "Management of invasive squamous cell carcinoma of the bulbomembranous male urethra with co-ordinated chemo-radiotherapy and genital preservation." Br J Urol. 1996 Oct;78(4):573-8.
** Suprapubic urinary diversion followed by 45 Gy in 25 fx to penis, perineum, regional lymphatics w/ concurrent Mitomycin C and 5FU.
* UPDATE at AUA 2005 (Medscape Review):
** 14 pts tx'd from 1991-2004. T2-4 dz in distal or bulbomembranous urethra.
** 12/14 locally controlled. 1 pt died of metastatic dz. Urethral stricture common, often requiring urethral reconstruction.