PANCE Blueprint Genitourinary (4%)

• Most common GU malignancy (after prostate cancer); most common type: urothelial (transitional cell) carcinoma — 90%
• Risk factors: cigarette smoking (#1 risk factor), occupational exposure (dyes, aniline, benzidine, arsenic), cyclophosphamide (hemorrhagic cystitis → bladder cancer), chronic Foley catheter, Schistosoma haematobium (squamous cell — Middle East/Africa)
• Classic presentation: painless gross hematuria in an older smoker
• DX: Cystoscopy with biopsy — gold standard; urine cytology; CT urogram for upper tract

TX:

• Superficial (Ta, T1): TURBT (transurethral resection) + intravesical BCG (bacillus Calmette-Guérin) immunotherapy
• Muscle-invasive: radical cystectomy ± neoadjuvant chemotherapy (cisplatin-based)

3D medical animation still showing urinary bladder cancer.

Penile cancer is a rare squamous cell carcinoma of the penis associated with poor hygiene and HPV infection

• Rare; squamous cell carcinoma most common (95%)
• Typically presents in uncircumcised men >50 with a painless ulcer, mass, or verrucous lesion on the glans or prepuce ± foul discharge or bleeding
• Strongly associated with HPV types 16 & 18, phimosis, poor hygiene, smoking, and chronic inflammation (e.g., balanitis)
• Lesion is often non-healing, indurated, and may progress to inguinal lymphadenopathy (key prognostic factor)
• Differentiated from benign lesions (e.g., condyloma) by ulceration, firmness, and persistence
• Classic presentation = painless penile lesion/ulcer or mass, often on glans or prepuce; foul-smelling discharge; inguinal lymphadenopathy (late)

DX: Diagnosis is made with biopsy (definitive); imaging (CT/MRI) used for staging and nodal involvement

• Early disease confined to glans/prepuce vs advanced disease with regional lymph node spread → worsens prognosis

TX: Surgical excision (partial or total penectomy, depending on stage) with sentinel lymph node biopsy or lymphadenectomy if nodal disease is present

• Radiation or chemotherapy for advanced/metastatic disease; topical 5-FU or imiquimod may be used for carcinoma in situ
• Prevention includes neonatal circumcision, improved hygiene, smoking cessation, and HPV vaccination (reduces risk of HPV-associated disease)

Penile tumor with left Inguinal lymphadenopathy

ReelDx Virtual Rounds (Prostate cancer)

Symptoms include difficulty with urination (obstructive symptoms), but most patients are asymptomatic at the time of diagnosis.

• Most common cancer in men; second leading cause of cancer death in men (after lung) AND (excluding skin)
• Adenocarcinoma (95%); The most common site of origin is the peripheral zone (the area furthest from the urethra and easiest to palpate on DRE)
• Risk factors: age (most important), Black race (highest incidence/mortality), family history, BRCA2 mutation
• On DRE, carcinoma is characteristically hard, irregular, and nodular (vs. BPH — rubbery, smooth, diffusely enlarged)

The primary tumor marker is Prostate-Specific Antigen (PSA). Note that PSA is organ-specific, not cancer-specific (it is also elevated in BPH, prostatitis, and after recent ejaculation or vigorous exercise)

• PSA is considered normal < 4 ng/mL
• PSA > 4 ng/mL: High suspicion for prostate cancer, BPH, or prostatitis
• PSA >10 = high risk
• PSA velocity (rising PSA) more predictive than single value

DX: Modern workup uses a combination of PSA, DRE, and increasingly multiparametric MRI (mpMRI) to reduce unnecessary biopsies

• If PSA level > 10 ng/mL: TRUS with biopsy is indicated, regardless of DRE findings
• If DRE is abnormal (nodular/hard): TRUS with biopsy is indicated, regardless of PSA level
• If PSA is 4.1 to 10.0 (The "Gray Zone"): Consider a multiparametric MRI (mpMRI) first. If MRI shows a suspicious lesion, a fusion biopsy is recommended
• Definitive Diagnosis: Transrectal ultrasound (TRUS) guided needle biopsy

TX: Treatment is individualized based on the Gleason Score (grades the aggressiveness of the tumor cells), stage, and life expectancy

• Low-risk/Slow-growing: Active Surveillance is the preferred management for many low-grade tumors (regular PSA and DRE monitoring)
• Localized Disease: Radical prostatectomy or radiation therapy (External Beam or Brachytherapy)
• Metastatic Disease: Androgen Deprivation Therapy (ADT) is the mainstay (e.g., Leuprolide or orchiectomy)
• Common Metastasis: Prostate cancer commonly spreads to the bone (axial skeleton); these are classically osteoBLASTIC (appearing white/dense on X-ray) — distinguishes prostate from most other cancers (which cause lytic lesions)
• Radical Prostatectomy - complication is erectile dysfunction!
• Monitor PSA should be less < 0.1

A 22-year-old male who develops a firm, painless, non-tender testicular mass with elevated serum β-HCG

Testicular cancer is the most common solid malignancy in young men ages 15-40 (average age 32 years old), usually a germ cell tumor (seminoma or nonseminoma).

• Presents as a firm, painless, non-tender testicular mass, and a feeling of heaviness in the scrotum, does NOT transilluminate (distinguishes from hydrocele)
• Risk factors: cryptorchidism (#1 risk factor) (risk remains even after orchiopexy), family history, prior testicular cancer, and infertility
• Types:
  • Seminoma (↑ β-hCG, radiosensitive, better prognosis)
  • Nonseminoma (↑ AFP ± β-hCG, more aggressive)
• Spreads to retroperitoneal para-aortic lymph nodes first (not inguinal unless scrotal violation)
• May present with gynecomastia (β-hCG effect) or symptoms from metastases (e.g., back pain, cough)

DX: Scrotal ultrasound (initial test) showing a solid mass → radical inguinal orchiectomy (We do NOT biopsy the testicle first → biopsy risks tumor seeding and spreading cancer via lymphatics)

• Key labs: AFP (never elevated in seminoma), β-hCG, and LDH (tumor burden/prognosis)

💡AFP elevated = NSGCT (never in pure seminoma) — this is the most board-tested tumor marker distinction in testicular cancer!

TX:  Radical inguinal orchiectomy followed by stage-based management (surveillance, chemotherapy [e.g., chemotherapy bleomycin/etoposide/cisplatin (BEP)], or radiation for seminoma)

• Prevention includes early orchiopexy for cryptorchidism and monthly testicular self-exam'

Left testicular seminoma, hypoechoic nodule, ultrasound image