Bladder and Upper Urinary Tract Cancers PDF

Bladder and Upper Urinary Tract Cancers Cevdet Kaya MD. Professor of Urology  Learning Outcomes Staging is  Able to list the risk factors of bladder and upper urinary tract cancers  Able to...

Bladder and Upper Urinary Tract Cancers Cevdet Kaya MD. Professor of Urology  Learning Outcomes Staging is  Able to list the risk factors of bladder and upper urinary tract cancers  Able to stage bladder and upper urinary tract cancer accurately  Can list the differences between bladder and UUT cancers  Able to list step by step current treatment strategies  Analyze the treatment alternatives based on the clinical and the histopathological parameters  Overview – Epidemiology – Risk Factors – Evaluation – Staging – Grading  Current Treatment Strategies –Transurethral Resection of Bladder Tumor (TURBT) – Intravesical Therapy – Radical Cystectomy – Chemotherapy and Radiation – Urinary Diversions – Robotic Approaches Cancer Biology  Cancer Biology  Cancer Cells  Growth without any stimulation  No response to stimuli for programmed cell death  Ability to invade both the surrounding and distant organs  Neovascularization  Defending against immune system  Genetic deletion and duplication  Carcinogens, Genetic disease, DNA damage  Heredity 5 CYBH Sifiliz  Bladder & Upper Urinary Tract Cancer The common point  the histology (transitional cell epithelium)  the continuity and anatomical relationship The difference between cancer of these two organs  The treatment strategy differs  Affecting the kidney in UUT cancer 17  Bladder Cancer 4th most common cancer in men in 2014 74690 new cases and 15,580 deaths in 2014 Represents 7% of all cancers and 3% of all cancer deaths M:F = 3:1 (survival better in men) Peak incidence ages 60-70 Majority (~93%) are urothelial cancer (transitional cell carcinoma)  Bladder Cancer Risk Factors Exogenous Industrial Schistosomiasis Aniline dyes Tobacco Benzene derivatives Cytostatics Phenacetin metabolites (aromatic (Cyclophosphamides) amines) ? Sweeteners (Saccharin, Paints, oils, gasoline cyclamate) Pelvic radiation Blackfoot disease (Taiwan) A. Fangchi (Chinese herb) Endogenous Trytophan metabolites Chronic irritations Nitrosamines (catheters) /Toxins Chronic inflammation  Occupations at Risk –Dry cleaners – Painters – Autoworkers – Truck drivers – Paper manufacturers – Metal workers – Hairdressers – Tire, rubber, chemical and petroleum workers  Symptoms and Signs Gross hematuria most common (intermittent)  Gross 68-97%  Microhematuria 11% Timing of hematuria  Initial (suggests urethral source)  Terminal (posterior urethra, bladder neck, prostate)  Continuous (bladder etiology) Irritative voiding symptoms Lumbar and suprapubic pain  Diagnosis Cystoscopy Urinary Tumor Marker  Usually cytology Imaging  Renal Ultrasound and IVP traditionally  Now CT Urogram  Even MR Urogram Transurethral Resection of Bladder Tumor and exam under anesthesia  Staging 70% non-muscle invasive (superficial)  Despite adequate therapy, 60-70% recur and 10-20% progress  70% Ta and 30% T1 25% muscle-invasive  5 year overall survival 78% (45% with + nodes)  Morbidity of treatment (cystectomy +/- chemotherapy)  Majority present as muscle-invasive initially 5% metastatic disease  Chemotherapy produces median survival of 18 mo  Treatment and Prognosis Stage Low grade vs high grade Single vs multiple Papillary vs solid Smaller vs larger tumor Carcinoma in situ (CIS) Up to 70% will recur within 5 yrs  Surgical Therapies for Bladder Ca Low grade, Ta or T1 disease  Surveillance  Possible intravesical therapy High grade (cIS, Ta, T1)  Repeat TURBT  Intravesical therapy Muscle-invasive disease (T2)  Cystectomy and urinary diversion Lymph Node/Distant Metastases (N+/M+) 25  Chemotherapy +/- radiation  Surgical Therapies for Bladder Ca Transurethral resection of bladder tumor Intravesical Therapy Radical Cystectomy  +/- Neoadjuvant Chemotherapy  Trimodal Therapy (XRT, Chemo, Surgery) Urinary Diversions Robotic Approaches to Bladder Surgery  Partial Cystectomy  Radical Cystectomy 26  Upper Urinary Tract Cancer Upper urinary tract urothelial cancers are uncommon (only 5–10% of Ucs) Pyelocaliceal tumours are approximately twice as common as ureteral tumours and multifocal tumours are found in approximately 10–20% of cases UTUC patients were predominantly male (70.5%) and 53.3% were past or present smokers. The majority of patients (58.1%) were evaluated because of symptoms, mainly visible haematuria A history of BC is associated with a higher risk of developing UTUCs  Upper Urinary Tract Cancer  2/3 of patients who present with UTUCs have invasive disease at diagnosis compared to 20% of patients presenting with muscle-invasive bladder tumours  9% of patients present with metastasis  Peak incidence in 70–90 years and are twice as common in men  A history of BC is associated with a higher risk of developing UTUCs  Upper Urinary Tract Cancer  Genetic  Tobacco exposure  The presence of arsenic in drinking water  Aristolochic acid produced by aristolochia plants, lead predominantly to UTUC  Aristolochic acid has been linked to BC, renal cell carcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma  Alcohol consumption  Upper Urinary Tract Cancer  Histological types  UUTC s are almost always UCs  pure non-urothelial histology is rare  Histological subtypes present in 25% of UTUCs  Pure squamous cell carcinoma associated with chronic inflammatory diseases and infections arising from urolithiasis  Urothelial carcinoma with divergent squamous differentiation in 15% of cases  Keratinising squamous metaplasia of urothelium risk factor for squamous cell cancers  Upper urinary tract UCs with different subtypes are highgrade and have a worse prognosis compared with pure UC  Other subtypes, although rare, include sarcomatoid and UCs with inverted growth  Upper Urinary Tract Cancer  The most common symptom is visible or nonvisible haematuria (70–80%)  Flank pain, due to clot or tumour tissue obstruction or less often due to local growth, occurs in approximately 20–32% of cases  Systemic symptoms (anorexia, weight loss, malaise, fatigue, fever, night sweats, or cough) should prompt evaluation for metastases  Upper Urinary Tract Cancer  Computed tomography (CT) urography has the highest diagnostic accuracy with a sensitivity of 92% and a specificity of 95%  Epithelial “flat lesions” without mass effect generally not visible with CT  Enlarged LNs is highly predictive of metastases  Magnetic resonance (MR) urography indicated in patients who cannot undergo CT urography, usually when radiation or iodinated contrast media are contraindicated  Upper Urinary Tract Cancer The sensitivity of MR urography is 75% after contrast injection for tumours < 2 cm. Computed tomography urography is more sensitive and specific for the diagnosis and staging of UTUC compared to MR urography 18F-Fluorodeoxglucose positron emission tomography/computed tomography (FDG- PET/CT) for the detection of nodal metastasis in 117 surgically-treated UTUC patients reported a promising sensitivity and  Upper Urinary Tract Cancer The sensitivity of MR urography is 75% after contrast injection for tumours < 2 cm. Computed tomography urography is more sensitive and specific for the diagnosis and staging of UTUC compared to MR urography 18F-Fluorodeoxglucose positron emission tomography/computed tomography (FDG- PET/CT) for the detection of nodal metastasis in 117 surgically-treated UTUC patients reported a promising sensitivity and  Upper Urinary Tract Cancer Urethrocystoscopy is an integral part of UTUC diagnosis to rule out concomitant BC Abnormal cytology may indicate high-grade UTUC when bladder cystoscopy is normal, and in the absence of CIS in the bladder and prostatic urethra [1, 90, 91]. Cytology is less sensitive for UTUC than bladder tumours and should be performed selectively for the affected upper tract In a recent study, barbotage cytology  Upper Urinary Tract Cancer Barbotage cytology taken from the renal cavities and ureteral lumina is preferred before application of a contrast agent for retrograde ureteropyelography as it may cause deterioration of cytological specimens. Retrograde ureteropyelography remains an option to detect UTUCs The sensitivity of fluorescence in situ hybridisation (FISH) for molecular abnormalities characteristic of UTUCs  Upper Urinary Tract Cancer These promising results suggest that URS might be avoided in selected patients with a positive urine biomarker test. However, further confirmation in comparative trials will be needed. Technical developments in flexible ureteroscopes and the use of novel imaging techniques may improve visualisation and diagnosis of flat lesions Presence, appearance, multifocality and size of  Upper Urinary Tract Cancer Prior to any treatment with curative intent, it is essential to rule out distant metastases. Computed tomography is the diagnostic technique of choice for lung- and abdominal staging for metastases. A SEER analysis showed that approximately 9% of patients present with distant metastases  Upper Urinary Tract Cancer Many prognostic factors have been identified and can be used to risk-stratify patients in order to decide on the most appropriate local treatment (radical vs. conservative) and discuss peri-operative systemic therapy. Factors can be divided into patient-related factors and tumour-related factors. Age and gender, Ethnicit, Genetic pre-disposition, Tobacco consumption, Surgical delay, High comorbidity and performance indices scores  Upper Urinary Tract Cancer Molecular markers Because of the rarity of UTUC, the main limitations of molecular studies are their retrospective design and, for most studies, small sample size. None of the investigated markers have been validated yet to support their introduction in daily clinical decision making  Upper Urinary Tract Cancer Kidney-sparing surgery for low-risk UTUC reduces the morbidity associated with radical surgery (e.g., loss of kidney function), without compromising oncological outcomes. In low-risk cancers, it is the preferred approach as survival is similar to that after RNU Endoscopic ablation should be considered in patients with clinically low-risk cancer [201, 202]. A flexible ureteroscope is useful in the management of  Upper Urinary Tract Cancer Segmental ureteral resection with wide margins provides adequate pathological specimens for staging and grading while preserving the ipsilateral kidney. Lymphadenectomy can also be performed during segmental ureteral resection. Segmental resection of the proximal two-thirds of ureter is associated with higher failure rates than for the distal ureter  Upper Urinary Tract Cancer Open radical nephroureterectomy Open RNU with bladder cuff excision is the standard treatment of high-risk UTUC, regardless of tumour location (LE: 3). Radical nephroureterectomy must be performed according to oncological principles preventing tumour seeding. Section 7.2.5 lists the recommendations for RNU Laparoscopic RNU is safe in experienced hands  Upper Urinary Tract Cancer Bladder cuff management Resection of the distal ureter and its orifice is performed because there is a considerable risk of tumour recurrence in this area and in the bladder [195,207,235-237]. Several techniques have been considered to simplify distal ureter resection, including the pluck technique, stripping, transurethral resection of the intramural ureter, and intussusception. None of these techniques has  Upper Urinary Tract Cancer Lymph node dissection The use of a LND template is likely to have a greater impact on patient survival than the number of removed LNs. Template-based and completeness of LND improves CSS in patients with muscle-invasive disease and reduces the risk of local recurrence. Even in clinically and pathologically node-negative patients, LND improves survival. The risk of LN metastasis increases with advancing tumour stage. Lymph  Upper Urinary Tract Cancer The primary advantage of neoadjuvant chemotherapy (NAC) is the ability to give cisplatin- based regimens when patients still have maximal renal function. Several retrospective studies evaluating the role of NAC have shown evidence of pathological downstaging and complete response rates at RNU [170,248-251] with a direct impact on OS. Furthermore, NAC has been shown to result in lower disease recurrence- and mortality  Upper Urinary Tract Cancer Metastatic disease Patients fit for cisplatin-based combination chemotherapy Patients unfit for cisplatin-based combination chemotherapy Maintenance therapy after first-line platinum-based chemotherapy Immunotherapy Other immunotherapies such as nivolumab , avelumab [293,294] and durvalumab have shown objective response rates ranging from 17.8% to 19.6% and median OS ranging from 7.7 months to 18.2 months in patients with platinum-resistant metastatic UC. These results were obtained from single-arm phase I or II trials only and the number of UTUC patients included in these studies was only specified for avelumab (n = 7/15.9%) without any subgroup analysis based on primary tumour location Upper Urinary Tract Cancer Upper Urinary Tract Cancer Upper Urinary Tract Cancer  Upper Urinary Tract Cancer T - Primary tumour TX Primary tumour cannot be assessed T0 No evidence of primary tumour Ta Non-invasive papillary carcinoma Tis Carcinoma in situ T1 Tumour invades subepithelial connective tissue T2 Tumour invades muscularis T3 (Renal pelvis) Tumour invades beyond muscularis into peripelvic fat or renal parenchyma (Ureter) Tumour invades beyond muscularis into periureteric fat T4 Tumour invades adjacent organs or through the kidney into perinephric fat N - Regional lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node 2 cm or less in the greatest dimension N2 Metastasis in a single lymph node more than 2 cm, or multiple lymph nodes M - Distant metastasis M0 No distant metastasis M1 Distant metastasis TNM = Tumour, Node, Metastasis (classification).