Urothelial Cancer of the Prostate

Background

• 90% of cases of urothelial carcinoma of the prostate occur in patients with a history of urothelial cancer of the bladder, primarily bladder carcinoma in situ (CIS)
  • However, only 3% patients with primary urothelial cancer of the bladder develop prostatic urothelial carcinoma
    • In males undergoing radical cystectomy for urothelial cancer, 40% will be found to have urothelial carcinoma of the prostate
      • In patients undergoing cystectomy for bladder cancer, extension of the tumor into the prostatic urethra without stromal invasion does not carry an adverse prognosis
• Primary urothelial carcinoma of the prostate without bladder involvement is uncommon, accounting for 1-4% of all prostate carcinomas

Pathophysiology

• Most patients with urothelial carcinoma of the prostatic ducts and acini will have direct extension of the bladder cancer into the prostatic urethra; however, some patients will have pagetoid spread underneath normal-appearing urothelium at the bladder neck
  • Intraductal and infiltrating urothelial carcinoma involving the prostate tends to be seen in higher-stage bladder tumors

• Risk factors for prostatic urethral involvement include (5):
  1. Presence of bladder CIS
  2. Previous intravesical chemotherapy
  3. Multi-focal disease
  4. Tumours at the trigone or bladder neck
  5. High-risk NMIBC

TNM staging of Urethral Carcinoma (AJCC 8th edition§)

Prostatic urethra

• pTX: cannot be assessed
• pT0: no evidence of primary tumor
• pTa: non-invasive papillary carcinoma
• pTis: carcinoma in situ of the prostatic urethra, periurethra or ducts
  • Tis pu: Carcinoma in situ, involvement of prostatic urethra
  • Tis pd: Carcinoma in situ, involvement of prostatic ducts
• pT1: invasion of prostatic urethral subepithelial connective tissue
• pT2: invasion of prostatic stroma
  • In the bladder cancer TNM staging system, only patients with prostatic stromal invasion, either direct or indirect, are considered to have T4a-staged bladder cancer disease
  • Extension of the tumor into the prostatic urethra without stromal invasion is currently classified under the prostatic urethral section, not bladder
• pT3: invasion of peri-prostatic fat or bladder neck (extraprostatic extension)
• pT4: invasion of adjacent organs (example: bladder wall, rectal wall)

Penile urethra

• pTX: cannot be assessed
• pT0: no evidence of primary tumor
• pTa: noninvasive papillary carcinoma
• pTis: carcinoma in situ
• pT1: invasion of urethral subepithelial connective tissue
• pT2: invasion of corpus spongiosum
• pT3: invasion of corpus cavernosum
• pT4: invasion of adjacent organs (example: bladder wall)

Diagnosis and Evaluation

• Transurethral resection of the prostatic urethra
  • Primary method for detecting prostatic urethral carcinoma
    • For highest yield, prostatic urethral biopsies should include any suspicious area, as well as at 5 and 7 o’clock (precollicular area) especially at the level of the verumontanum, as this area contains the highest concentration of prostatic ducts
  • Indications:
    1. Positive urine cytology but a negative bladder biopsy
    2. Recurrent bladder cancer after multiple courses of intravesical chemotherapy
    3. Visible tumour in prostatic urethra

Management

• Based on the degree or depth of involvement
  • See 2015 CUA NMIBC Guideline Notes
    • pTis pu (CIS of the prostatic urethra) or visible prostatic urethra tumour concomitant with NMIBC of the bladder: TURP then BCG.
      • BCG is given after TURP for accurate staging and increasing efficacy by increasing surface area
    • pTis pd (CIS involving the prostatic ducts): treatment controversial, consider TURP + BCG
      • Despite good response to BCG, prostatic ductal involvement has potential for invasion, and if invasion occurs there is a high risk of metastasis.
    • Re-biopsy of the prostatic urethra is recommended after BCG to detect recurrences early
      • Recurrence of any HG lesion in prostatic urethra after TURP + BCG: consider radical cystectomy plus urethrectomy
        • If patient prefers bladder-sparing approach, consider repeat BCG or intra-vesical gemcitabine
    • pT2 (prostatic stromal invasion (pT2): radical cystectomy +/- urethrectomy
      • Consideration of urethrectomy should be made, especially if tumor is present near or at the surgical margin
  • Campbell’s:
    • For patients with non-invasive prostatic urethral cancer, TURP with BCG therapy is appropriate. For patients with prostatic ductal disease, complete TURP is warranted, plus BCG therapy
    • Prostatic stromal invasion is a poor prognostic factor and is treated with multimodal therapy combining chemotherapy and radical cystectomy

Prognosis

• 5-year survival varies by stage: up to 100% for those with urethral mucosal involvement; 50% with ductal/acinar/glandular involvement; and 40% with stromal invasion

Questions

1. What are the risk factors for urothelial carcinoma of the prostate?
2. What is the pT staging of a patient found to have bladder cancer invading the prostatic stroma?

Answers

1. What are the risk factors for urothelial carcinoma of the prostate?
   1. Presence of bladder CIS
   2. Previous intravesical chemotherapy
   3. Multifocal disease
   4. Tumours at the trigone or bladder neck
   5. High-risk NMIBC
2. pT4a

References

• Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 92