NC.com

Diagnosis

UTUC by the numbers

• Bilateral: 1-5%
• Multifocal: 10-20%
• History bladder cancer: 4-41%, depending on population
• Disease recurrence: 22-47% in bladder, 2-6% in contralateral renal unit
• Spread: 60% are invasive, 7% are metastatic

Risk Factors

• Lynch syndrome (HPNCC): suspect if UTUC and age < 60, or first degree relatives x2 with HPNCC-related cancers, Amsterdam II criteria (3+ relatives w/ HPNCC cancer, 2+ generations affected, 1+ tumors before 50yo)
• Tobacco: 2.5-7x increased risk
• Occupational: exposure to aromatic amines increases risk 4-5.5x
• Aristolochic acid (Chinese herb) nephropathy: Aristolochia fangchi produces compound that induces p53 mutation, resulting in ESRD and UTUC
• Arsenic: associated with UTUC and peripheral vascular disease (blackfoot)
• Inflammation: increased risk with chronic irritation (stones, UTI)

Workup

• Symptoms: hematuria (56-98%), flank pain (20-30%), lumbar mass (10%) - incidental diagnosis (15%)
• Cystoscopy: assess for associated bladder cancer
• CT urography: sensitivity 67-100%, specificity 93-99%
• Hydronephrosis: seen with invasive ureteral tumors in 80%
• Further imaging: obtain if concern for HG or invasive disease, obtain chest imaging on every patient, bone scan and brain imaging on select patients
• Genetic testing: 5% risk Lynch syndrome, check if < 60yo, personal/family hx UTUC or Lynch syndrome cancers

Conservative treatment

Organ-sparing management

• Warranted if low risk (needs all criteria): low grade pathology, no high grade cytology, papillary (not sessile), tumor < 1.5cm, solitary tumor, no invasion on iamging, no variant histology, no hydronephrosis, no prior cystectomy for HG bladder cancer
• Relative indications: for poor renal function, solitary kidney, poor surgical candidate, bilateral tumors

Endoscopic management

• Diagnostic ureteroscopy: beneficial for diagnosis (some treat based on imaging alone), can obtain tissue via biopsy (low false-negative rate), can be performed antegrade if necessary (potential risk of tract seeding), can use basket, laser, or loop resection
• Risks: stricture (5-25%, more common with cautery than laser), perforation (uncommon)
• Recurrence after endoscopy: 30-50% at 5yr, 20-30% will require NUx

Intracavitary therapy

• Indications: Ta, T1, or CiS
• Mitomycin hydrogel (Jelmyto): can administer antegrade/retrograde, stays in kidney then dissolves, administer weekly, 58% showed complete response at 3mo (56% sustained response at 12mo), ureteral stenosis is potential risk
• Jelmyto instillation tips: wait 3-4wks after endoscopic surgery, do not perform if perforation, check CBC each time, alkalinize urine (1.3g NaBicarb night before and morning of), measure renal pelvis volume with contrast
• Jelmyto side effects: ureteral stenosis (44%), UTI (32%), hematuria (31%), flank pain (30%), nausea (24%), myelosuppression (3%), contact dermatitis
• BCG: previously used but not currently recomended

Aggressive treatment

Nephroureterectomy

• Nephroureterectomy with bladder cuff is gold standard for any high-grade or invasive lesions, prevents ipsilateral recurrence (15-44%), low risk for contralateral recurrence (< 8%)
• Intravesical chemotherapy: give single dose mitomycin or gemcitabine immediately postoperatively to decrease risk for bladder cancer
• Not taking bladder cuff: recurrence risk 16-58%
• 5yr survival after nephroureterectomy: Ta/T1 60-90%, T2 43-75%, T3 16-33%, T4 0-5%, N1+ 0-4%, M1+ 0%

Other surgical options

• Indications: limited renal reserve, low grade/stage tumors easily removed, isolated tumor, cannot be adequately treated with endoscopic or intracavitary therapy alone
• Partial nephrectomy: need to be able to remove portion of collecting system without urine leak
• Segmental ureterectomy: reanastomose over a stent, avoid tumor spillage, distal tumors less likely to recur
• Distal ureterectomy with reimplant: use only for distal third of ureter, unclear benefit to non-refluxing reimplant
• Ureterectomy + ileal ureter: unable to remove via segmental ureterectomy, higher risk for complications

Lymph node dissection

• Indications: high grade, high risk, potentially invasive
• Volume: recommended to remove 8+ nodes to confirm pN0 status
• Pelvic ureter template: remove common/external/internal iliac, obturator nodes
• Left abdominal ureter and renal pelvis: remove renal hilar, paraaortic, interaortocaval nodes, from renal hilum down to aortic bifurcation
• Right abdominal ureter and renal pelvis: remove renal hilar, paracaval, retrocaval, interaortocaval nodes, from renal hilum down to caval bifurcation

(Neo)Adjuvant Chemotherapy

• Neoadjuvant: benefits based mainly off bladder cancer data, indicated if patient would not have adequate renal function for adjuvant chemotherapy
• Adjuvant: per POUT trial, improves disease-free survival, indicated if no neoadjuvant chemotherapy and pT2-T4 or N1-N3, can use gem/cis (GFR > 50) or gem/carbo (GFR < 50)
• XRT: minimal data, not usually indicated

Metastatic disease

• Management: systemic chemotherapy, consider NUx if adequately downstages afterwards
• XRT: indicated for symptom control
• For LN+ or metastatic disease, give chemotherapy and only consider surgery for good radiographic response
• Immunotherapy (PDL-1 inhibitors): may be warranted for neoadjuvant and post-chemo relapses