Upper Tract Urothelial Cancers Nephron Sparing Strategies Girish Kulkarni, MD, PhD, FRCSC Urologic surgeon, Division of Urology Princess Margaret Hospital, University Health Network Assistant Professor, Department of Surgery, Faculty of Medicine, University of Toronto Institute of Health Policy, Management and Evaluation University of Toronto Toronto, Ontario
Faculty Disclosure Statement Industry financial relationships for the 2-year period prior to ICUC: Honorarium/consultant fees/ grants: - Astellas, Janssen, Bayer Girish Kulkarni MD, PhD, FRCSC
Key Learning Objectives By participating in this session, health care professionals will: Understand the indications for and classification of organ preservation for upper tract urothelial carcinoma Appreciate the evidence for varied organ-preserving approaches and outcomes Understand published follow up recommendations postorgan preservation
Upper Tract Urothelial Cancers Nephron Sparing Strategies Girish Kulkarni, MD PhD FRCSC Assistant Professor, Division of Urology University Health Network
Conflicts of Interest None to declare
Learning Objectives Understand the indications for and classification of organ preservation for UTUC Appreciate the evidence for varied organpreserving approaches and outcomes Understand the published follow up recommendations post-organ preservation
Outline Why organ preservation Indications for organ preservations Organ-preserving approaches and outcomes Endoscopy BCG in the Upper Tract Segmental resection Partial nephrectomy Follow up after organ preservation
Gold Standard Treatment Nephroureterctomy with bladder cuff excision (NU) ± LND But. Impairment in renal function Impaired QOL Complications Higher costs Suriano and Brancato, Rev Urol 2014 Pak et al, J Endourol 2009
Why Organ Preservation Imperative vs Elective Solitary Kidney avoid dialysis (maintain QOL) Bilateral disease Maintain renal function Candidacy for chemotherapy High perioperative risk with NU Potential for recurrent disease Lynch Syndrome Balkan nephropathy Arsenic exposure Smoking Analgesic abuse
Classifying Organ Preservation Endoscopic Retrograde Antegrade (percutaneous access) Endoscopic plus adjuvant therapy (BCG) Segmental resection Partial nephrectomy
When to Consider Endoscopic Approaches EAU Guidelines (no AUA or CUA guidelines exist) Depends on technical constraints, tumour factors and surgeon expertise Tumour factors: size, focality, grade Roupret et al, Eur Urol 2013
Treatment Algorithm Roupret et al, Eur Urol 2011
Diagnosis H&P, Cystoscopy, CT/MRI, RGP + ureteral washings, URS + biopsy Need for tissue to determine optimal technique URS and biopsy mandatory Needed for grade of tissue stage and recurrence risk correlate Grade determination in 75-90% of cases El-Hakim et al, Urol 2004 Keeley et al, J Urol 1997
Diagnostic Accuracy: Bx and Cyto Urol Oncol 2012 Comparison of preop bx and cyto grade with NU specimens in 77 pts Test characteristics of Bx and cyto together: Overall Sensitivity to detect any tumour: 84% Sensitivity for High Grade: 83%
Test Characteristics 19/59 (32%) of high grade tumours detected as low grade and benign! Careful interpreting biopsy results
Endoscopic Approaches For low risk tumours Small Low grade tumours Unifocal Risk of understaging Requires closer follow up
Ureteroscopy Preferred method Maintains closed system (low risk of seeding) Less invasive Technique Re-biopsy and debulk with graspers or basket pathology Laser base (Nd:YAG or Ho:YAG) Disadvantages Small working channel Access to LP calyces Pyelolymphatic seeding Complications: 8-13%
Percutaneous Advantages Calyceal tumours difficult to access via URS Bigger tumours (larger instruments) Patients with diversions Disadvantages Theoretical seeding risk More invasive PCNL expertise Higher complication rate than URS (20-30%) Sorokin et al, Case Rep Urol 2013
Endoscopic Outcomes Suriano and Brancato, Rev Urol 2014
Radical nephroureterectomy versus endoscopic procedures for the treatment of localised upper tract urothelial carcinoma: A meta-analysis and a systematic review of current evidence from comparative studies str act R. Yakoubi a, P. Colin b, T. Seisen c,d,p.leon c,d, L. Nison e, G. Bozzini e, S.F. Shariat f, M. Roupr^et c,d, * a Department of Urology, Centre Hospitalier de Boulogne-sur-Mer, Boulogne, France b Department of Urology, Hopital Prive de la Louviere, Generale de Sante, Lille, France c AP-HP, Hopital Pitie-Salpetriere, Academic Department of Urology, F-75013 Paris, France d UPMC Univ Paris 06, GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancerologie, F-75005 Paris, France e Department of Urology, H^opital Claude Huriez, CHRU Lille, Universite Lille Nord de France, Lille, France f Department of Urology, Medical University of Vienna, Vienna, Austria 8 studies, all retrospective 1002 patients, 322 endoscopic vs 680 NU Accepted 19 June 2014 Available online - - - Higher grade and stage in NU patients Quality of studies poor EJSO 2014 The conservative management of upper tract urothelial carcinoma (UTUC) has seen important developments over the last 10 years wi ances in endoscopy. Our aim was to compare the available evidence regarding the impact of endoscopic nephron sparing procedur P) and radical nephroureterectomy (RNU) on survival of upper tract urothelial carcinoma (UTUC). A critical review of Pubmed/Me, Embase and the Cochrane Central Register of Controlled Trials was performed in July 2013 according to the preferred reporting item systematic reviews and meta-analysis (PRISMA) statement. Overall, eight publications were selected for inclusion in this meta-analys all of them were retrospective or non-randomised comparative studies. The primary end points were the overall and cancer-specifi vivals (OS and CSS) in the two treatment groups. We achieved to pool data on 1002 patients diagnosed with localised UTUC and treate er by endoscopic NSP (n ¼ 322) or by RNU (n ¼ 680). No significant difference was found in terms of OS and CSS between RNU an oscopic NSP (HR ¼ 1.47 and p ¼ 0.31; HR ¼ 0.96 and p ¼ 0.91, respectively). However, the low level of evidence (3b) and the he geneity of the studies limited the quality of the results. In the absence of prospective and randomised studies, the equivalent oncolog
Oncologic Outcomes OS CSS
Upper Tract Topical Therapy BCG or MMC after endoscopic management Administration: Antegrade (percutaneous tube) vs Retrograde (passive: JJ stent vs active: ureteral catheter) Adjuvant therapy or primary therapy for CIS
BCG for UTUC CIS Overall 32% recurrence rate Carmignani, Rev Urol 2014
Adjuvant therapy papillary disease BCG MMC 26.5% recurrence rate Carmignani, Rev Urol 2014
Segmental Resection Distal tumours >> Proximal tumours Distal ureterectomy + reimplant: high grade, large, invasive Ureteroureterostomy for proximal tumours Wide excision to ensure negative margins Lymph node dissection possible!
BJU Int 2012 416 NU vs 52 segmental ureterectomy Confirmed in SEER data Lughezzani et al, Eur J Cancer 2009 NU SU
Partial Nephrectomy Only if imperative For polar tumours, large, high grade or stage Few case series
8 patients with imperative indications Recurrence in 5/7 patients (1 lost to f/u) 1 metastatic death Conclusion: acceptable DSS Int J Urol 2014
Follow Up CUA Guidelines 2013 Table 1: Recommended protocol for follow-up after surgery for UTUC Pathology Investigations Number of months after surgery for UTUC LG pt<2 Nx/0 3 6 12 18 24 30 36 48 60 Hx and PE x x x x x x x x Blood work x x x x x x x x Urine cytology x x x x x x x x Cystoscopy x x x x x x x x CXR x x x x x CTU x x x x x +/-Ureteroscopy* x x x x x x x x LG pt2 Nx/0 HG pt<2 Nx/0 or LG/HG pt>2 or pn+ Hx and PE x x x x x x x x Blood work x x x x x x x x Urine cytology x x x x x x x x Cystoscopy x x x x x x x x CXR x x x x x x x CTU x x x x x x x +/-Ureteroscopy* x x x x x x x x Hx and PE x x x x x x x x x Blood work x x x x x x x x x Urine cytology x x x x x x x x Cystoscopy x x x x x x x x CXR x x x x x x x x x CTU x x x x x x x x x +/-Ureteroscopy* x x x x x x x x LG: low grade; HG: high grade; Hx: History; PE: physical examination; CXR: chest x ray; CTU: computed tomography urography; pt<2 includes ptis, pta and pt1; *Ipsilateral ureteroscopy with selective cytology or biopsy should be performed following nephron-sparing procedures *Ipsilateral URS with biopsy or cytology if nephron-sparing
Conclusions Nephron-sparing approaches for UTUC are feasible Many approaches tailored to grade and stage Evidence to date is weak