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.

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.