Radiation Oncology/Urethra

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.

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.