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.