Probability of non-organ confined disease, from Margulis et al
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)
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
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
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
References
AUA Core Curriculum
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Djaladat, Hooman, et al. "Reproductive organ involvement in female patients undergoing radical cystectomy for urothelial bladder cancer." The Journal of urology 188.6 (2012): 2134-2138.
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