Genitourinary Flashcards
Discuss the epidemiology for bladder/ureter cancer.
Incidence (Australian statistics)
- 3200 cases annually (2.1% of all new cancers)
- 11th most common malignancy, 4th most common in men
Marked male predominance (3:1)
Disease of the elderly -mean 70yo
Generally higher income nations & urban dwellers
5 year OS 50-60%
Trigone is most common site
75% of bladder cancers present as superficial disease
* 70% non-invasive papillary (Ta)
* 10% flat in-situ (Tis)
20% T1 invasive
* Previously TCC ○ Can involve urothelium from renal pelvis to urethra ○ Preinvasive/superficial disease > muscle invasive ○ Needs muscle in specimen to be certain of preinvasive/superficial disease ○ Can be further classified as non invasive vs invasive * General macro: ○ Most common sites: trigone (below VUJ), lateral and posterior wall, + bladder neck ○ Frequently multifocal dt field change and tumour seeding ○ Typically large infiltrative masses
Describe the risk factors for bladder/ureter cancer
Very rarely genetic, usually associated with exposure to carcinogens
1) cigarette smoking
* most important influence (3-5 fold increase in risk) (including SCC)
* 50-80% of bladder cancers are associated
* Critical with management od discuss smoking cessation with patient
* ?alcohol
2) industrial aryl amine (clothing dyes) & other industrial agents (e.g. paints, solvents), heavy metals
* 15+ year latency
4) cyclophosphamide exposure (TCC+SCC)
5) pelvic irradiation
6) reduced water intake
* Increasing intake may dilute carcinogens in urine –> reduce exposure
7) Chronic inflammation
* Chronic UTIs
* Chronic /long term IDC
* Bladder calculi
* Neurogenic bladder
8) Nephrolithiasis, anatomic anomalies eg. Horseshoe, duplicated renal pelvis (renal pelvis/upper tract SCC)
9) Bladder anatomical anomalies eg. diverticulum
Due to common risk factors, previous upper urinary tract carcinoma (ureter/renal pelvis) predicts for bladder cancer
Genetic
Slow acetylator – leads to impaired metabolism of amines
Lynch syndrome (esp MSH2) may be associated with increased risk (10%)
SCC RF: CHronic inflammation
schistosomiasis ○ Endemic in North Africa (esp Egypt) ○ Pathogenesis = parasitic worm--> organisms lay ova in epithelium --> chronic inflammation and metaplasia --> increased risk of bladder SCC (rather than TCC) * Chronic IDC –paraplegia, MVA. * Bladder stone, recurrent UTI * Cyclophosphamide
List the layers of the bladder.
i) Urothelium/epithelium– as above
ii) Lamina propria– separated from urothelium by thin basement membrane. Abundant connective tissue, loose stroma, blood vessels, thin bands of muscularis mucosa
iii) Muscularis propria (detrusor muscle)- surrounds lamina propria, thick irregularly arranged bands of detruser muscle. Smoothelin is a marker of terminally differentiated smooth muscle cells, specific for muscularis propria compared to muscularis mucosa so can be helpful in determining muscle invasion
Anchored to the abdominal wall by the urachus (embryological remnant)
iv) Serosa/Perivesical Fat – M propria is separated from perivesical fat by serosal layer.
Describe the pathogenesis for bladder cancer
1) papillary neoplasm
○ Chronic inflammation –cytokines, interleukin.
○ Gain of function mutations in FGFR3 and RAS pathways –> development of papillary NMIBC
○ Gain of further mutations which lead to muscle invasion (e.g. p53, RB)
▪ TERT, PI3K, other genetic instability
▪ Only 20% of lesions will progress to MIBC
2) carcinoma in-situ
○ Mutations in p53 +/- RB –> development of flat carcinoma in-situ within epithelium
▪ P53/RB mutations occur early in CIS
○ Gain of further mutations which lead to muscle invasion
▪ PTEN
▪ Much higher incidence of progression to MIBC
Discuss the theories for multifocality
The presence of a bladder or upper renal tract cancer strongly predicts for future disease
1) Field cancerisation Due to equal carcinogenic distribution, all areas are likely to have mutational damage ○ Therefore, high risk of further disease occurring elsewhere in bladder (50% recurrence after TURBT) ○ This also extends to risk of ureter/urothelial involvement Extensive disease involvement (or multiple recurrence) should indicate cystectomy as the preferred approach 2) Monoclonal seeding Malignant cells spread via intraluminal lymphatics and re-implant ○ A seemingly new tumour deposit takes shape Clinical evidence ○ If you have upper tract disease, you have 40% risk of bladder but 5% of contralateral upper tract
Describe the different types of non-invasive bladder histology
WHO classification
○ 2004/2022 update
○ G1/2/3 > PUNLMP > LG >HG
○ Aggressive subtypes: Micropapillary, nested, large nested
* Papilloma (1% of all bladder tumours) ○ Small and single causes haematuria ○ Benign ○ Exophytic papilloma = malignant progression rare (but possible) ○ Exophytic lesions w papillary fronds lined by urothelium lacking atypia. ○ Inverted papilloma = benign * Papillary urothelial neoplasm of low malignant potential (PUNLMP) ○ Papillae lined by thickened urothelium with ↑cell density. Mitoses rare. ○ Recurrence is reasonably frequent ○ Progression to malignancy is rare * Low-grade papillary urothelial carcinoma (non-invasive - Ta) ○ Slightly abnormal architecture in urothelium and low-grade atypia ○ Tendency to recur locally, but infrequently (10%) invade muscle ○ Rarely result in death as a result * High-grade papillary urothelial carcinoma (non-invasive - Ta) ○ Dyscohesive cells with irregular nuclei; frequent mitoses; disordered architecture ○ Markedly higher risk of progression to MIBC 65%. 10 year survival 40% ○ High risk of nodal and distant metastasis * Carcinoma in-situ ○ High grade lesion w cytologically malignant cells within a flat urothelium that have not invaded lamina propria. ○ Often asymptomatic, but may present with dysuria, urgency, haematuria. ○ MACRO – Irregularly hyperaemic mucosa. Commonly multifocal + may involve most of bladder surface, extending into ureters + urethra. ○ MICRO – severe cytologic atypia w nuclear anaplasia, loss of polarity, crowding, pleomorphism. Umbrella cell urothelium retained ○ If untreated >50% chance of progression to invasive malignancy
Describe the pathology for invasive urothelial carcinoma
- Invasive urothelial carcinoma (90%)
○ Classified by Papillary or flat, and high or low grade.
○ Depth of invasion is prognostic (and defines T-stage)
○ 80% of high grade lesions invade muscle
○ Ta, Tis and T1 are nonmuscle invasive.
○ Macroscopic Appearance
* Trigone, field changes, multifocality.
* Ranges from subtle bladder wall thickening, to obvious exophytic/ulcerated mass, esp trigoneMicroscopic Appearance * Cytologic appearance ○ Standard irregularities (high nuclear/cytoplasm ratio, irregular chromatin, hyperchromatic nuclei, bizarre mitoses) ○ Degree of changes indicates grade * Histology ○ Flat or Papillary: urothelium around fibrovascular cores ○ Neoplastic cells typically arranged in nests/sheets/cords ® Invading past Lamina propria ○ Can have single irregular cells within otherwise normal appearing structure ○ High grade hyperchromatic nuclei, enlarged, mitosis, necrosis mmunohistochemistry ○ POS = GATA3, CK7, CK20, p40, p63, HMWCK NEG = PSA & NKX3.1 & AMACR (prostate), PAX 8 (RCC)
List the rare subtypes of bladder TCC.
- Rare subtypes
○ Lymphoepithelial-like carcinoma
○ Microcystic carcinoma
○ Plasmacytoid carcinoma (impart poor prognosis) –> loss of E-cadherin (discohesive)
○ Micropapillary carcinoma (impart poor prognosis)
○ Sarcomatoid carcinoma (impart poor prognosis)
PMS is bad
Besides TCC what are other primary bladder tumour?
- Squamous Cell Carcinoma (SCC)
○ Epidemiology
§ Uncommon - 3-5% of bladder cancers
§ Incidence varies by geographic region, with higher prevalence (30%) in Egypt and Africa due to schistosomiasis
· Incidence is falling due to declining rates of schistosoma infection
§ Slight male predominance
○ Risk factors
§ Chronic inflammation
· Chronic catheter
· Neurogenic bladder
· Bladder stones
· Schistosomiasis
§ Smoking – x5 increased risk
○ Histopathology
§ Macro: Usually large exophytic tumours, some cases flat and ulcerating. Tan/white colour. Often necrotic with flaky keratin on surface
§ Micro: Irregular infiltrating nests or sheets of malignant cells with destructive stroma invasion. Keratin pearls/ intercellular bridges, often associated with SCC insitu.
§ If any focus of urothelial carcinoma is present, then tumour is defined as urothelial carcinoma with squamous differentiation- Adenocarcinoma
○ Rare
○ Associated with remnant urachus or in association with extensive intestinal metaplasia
○ More often secondary vs. primary (rectum, prostate, endometrium) - Small Cell Carcinoma
○ Rare
○ Aggressive natural history, associated with p53 or Rb mutations - Rhabdomyosarcoma
○ Exceedingly rare –> childhood cancer predominantly
Typically present with large masses protruding into lumen - Benign lesions:
§ Cystitis, metaplasia
® Infectious, iatrogenic, idiopathic
® Can form polyploid features
® Generally not premalignant
§ Malakoplakia: distinctive chronic inflammatory reaction
§ Nephrogenic adenoma: implantation of renal tubular cells into inflammaed urothelium
§ Urothelial papilloma: uncommon
Can invert and ivaginate into the lamina (no invasion)
- Adenocarcinoma
Describe the patterns of spread for bladder cancer.
Patterns of Spread
a) Local
* Often multifocal, can recur in previously uninvolved quadrants. May involve most of the bladder surface, ureters and urethra.
Multifocality due to 2 main reasons:
i) Tumour cells have ability of autotransplantation, hence multifocality.
ii) Field cancerisation, so recurrences are new tumours rather than true recurrences.
* Muscle invasion usually signifies high grade tumour + assoc w worse prognosis: 50% survival at 5yrs.
* Direct spread to pelvic side wall, vagina/uterus, rectum, prostate.
b) Lymphatic
* Drainage to perivesical LNs (1st ech)→ int + common iliacs. Some to ext iliacs.
* Macroscopically +ve LN generally v poor prognosis; precludes definitive treatment.
* However, some series evidence from radical cystectomy pts w pelvic LND, that 25% of pts w involved LN survive 10yrs. Also, pts who have a PLND have better survival than those that don’t, + pts w 10+ LNs dissected have better survival than <10 LNs (Case series)
* Note: TROG protocol- if ↑LNs on CT, then only eligible if LNs -ve on biopsy.
c) Haematogenous: Bone, lung + liver.
Discuss the recurrence risk factors and risk characterisation for non-muscle invasive bladder cancer.
Risk of Recurrence (superficial bladder cancer)
* 40-80% NMIBC recur within 6-12 months without additional therapy
* 10-15% will progress to MIBC, regional or met
* General:
○ Stage
○ Grade
○ Multifocality
○ Frequency of recurrence
○ Size
○ Presence of CIS
○ Variant histo
○ LVI
* Low-risk = all of: ○ solitary, primary (non-recurrent), low-grade Ta papillary carcinoma, <3cm ○ no CIS * Intermediate-risk ○ Not meeting either criteria = ○ Low grade papillary with some of multiple lesions, recurrent disease, >3cm * High-risk = any of: ○ CIS ○ High-grade Ta papillary carcinoma ○ T1 disease
Describe the prognostic factors for muscle invasive bladder cancer
Patient
* Age and performance status
* Co-morbidity (notably, renal function)
* Anaemia
* Smoking (impaired tumour control and worse toxicity)
* Ability to have surgery
Tumour
* T-stage is the most significant
○ T1 to T2 distinction most important
○ T2 50% survival at 5 years (75% T1, 20% T3)
○ Size is also relevant for outcome with CMT
* N-stage also important
○ N+ disease is considered metastatic
○ Risk of nodal increases w/ T stage (T1 – 5%; T2-3a – 30%; T3b – 50%; T4 – 60%)
* Histological grade, LVI
* Hydronephrosis
* Recurrent disease
* Various histopathological variants impart different prognosis
* Associated CIS - risk of MIBC 30% at 5 years
Treatment
* Concurrent chemotherapy (ideally cisplatin-based)
* Extent of TURBT (completeness of resection)
* Residual disease after TURBT
What factors should be considered when deciding on bladder preservation therapy.
- “Bladder Worth Preserving”
○ Continent
○ Good bladder capacity- Unifocal T2-3a disease only
○ In addition, lesions >5cm have worse prognosis - Maximal TURBT associated with improved outcome
- Absence of tumour associated hydronephrosis
Absence of extensive CIS (field cancerisation)
- Unifocal T2-3a disease only
Describe the history and examination for a patient with bladder cancer.
- History
○ HPI
§ Haematuria (painless in 80%) - micro or gross (usually gross)
□ Initial suggest urethral
□ Terminal suggests bladder neck or prostate
□ Continuous suggests bladder
§ Microscopic haematuria
□ –urologist/cystoscopy if age >40-50, smoker or gross haematuria
§ Bladder function
□ Irritative bladder symptoms: dysuria, frequency, urgency (especially in the absence of a UTI)
® Especially CIS
§ Suprapubic pain (direct tumour invastion/obstruction)
§ Pelvic pain
□ Obturator, hypogastric, rectal, presacral invasion or urogenital diaphgragm
§ Obstructive symptoms
□ Flank pain
□ LUTS if prostate/bladder neck (less common)
○ PMHx
§ Previous ureteric/bladder diagnosis (e.g. chronic cystitis)
§ Pelvic radiotherapy
§ Chemotherapy (esp cyclophosphamide)
§ Chronic UTIs–> chronic irritation of the bladder
○ Family History
§ Lynch syndrome
○ Social
§ Ethnic background (Africa/Egypt areas in which chronic infection with schistosoma has an association with chronic inflammation and SCC)
§ Smoking history (Most dominant risk factor- Increase RR x5)
§ Occupational exposures
□ Hair dyes
□ Paint
□ Petroleum
Describe the staging for bladder cancer.
○ NMIBC (70%): Superficial low-grade tumors (Ta, T1).
○ Of those, 70% are confined to mucosa (Tis/Ta). 30% are confined to submucosa (T1).
○ 15-20% develop MIBC after diagnosis.
○ MIBC (25%): Invasion of the detrusor muscle. Around 50% will develop metastases, even with local therapy.
○ 4% with mets at diagnosis.
Risk of nodal involvement
○ Overall 24% LN+.
○ Lymph nodes for T0-1 / 2 / 3a / 3b-4
○ of 5→ 18→ 26→ 50%
○
TNM Staging (8th edition)
Ta-T1 = superficial
>=T2 = MIBC
Describe the work up for bladder cancer.
Work-Up
- Urine cytology (12-60% sensitive; high specificity) (not if catheter) ○ If high-index of suspicion, proceed to cystoscopy ○ If cystoscopy negative, urine cytology to exclude upper tract malignancy - Bloods (pre-surgical/pre-chemotherapy) ○ FBC, EUC, CMP, LFT - Urine MCS - exclude UTI, exclude haematuria mimics by seeing RBC ○ Prior to cystoscopy ○ Prior to intravesical therapies - Imaging: ○ Renal tract USS often in initial workup § Can miss small tumours, especially if less than 10mm § False positives with inflammation or underfilling ○ CT CAP –good for bladder masses. Only 70% sensitive for nodes. § Used for initial imaging where possible ○ CT IVP for renal pelvis and ureter lesion - exclude synchronous § Prioritises the excretory phase and contrast is timed to best image the kidney and ureters § At least 3 phases with delayed excretory phase (IVP) □ 87% sensitivity, 99% specificity § Good for upper tract abnormalities and potential met disease § Not good for muscle invasion § Contrast timing is less intentional for imaging the urinary tract ○ Bone scan ○ MRI to assess tumour extent § Not rebated § Suitable for contrast allergy § Distinguish T1 from T2; also better for T3 § Needs to be done before TURBT ○ FDG-PET (rare cancer MBS item) § Changes management in 10% - EUA + Cystoscopy ○ EUA first - assess for fixation, if so - not resectable ○ Biopsy (aim TURBT) 4 quadrants + urethra § Urethra involvment = contraidindication for intravesical therapy. § Usually piecemeal, en bloc resection better - limited by size (needs to be able to come out with c'scope) § Cold cup biopsy -no diathermy, then diathermy after to stop bleeding § Resectascope -loop resection with plasma arc -cuts/coagulates □ Need 3 way catheter after to stop clot -dilutes with saline § Generally will put in stent at time of TURBT ○ § Risks - □ Anaesthetic, bleeding, clots, UTI, pain □ Damage to bladder, Ureter (obstruction from ureter) □ Incomplete resection □ Seeding of infection ○ Bilateral Ureter cytology ○ Fluorescence: instilled 1 hour before. More sensitive for tumour § Improves recurrence free survival § Good for CIS ○ Need muscle present in biopsy specimen ○ Important to assess for CIS: o If present, increased risk of MIBC o Assoc with aggressive disease o Less likely to have durable response to BCG ○ Important to assess for hydronephrosis: o Associated with MIBC in 90% cases o Assoc with 70% extravesical spread o Less likely to achieve CR - FU after TURBT should biopsy TURBT site.
Describe the general initial management for bladder cancer.
- Patients should all have a cystoscopy with maximal TURBT (including non-MIBC)
○ TURBT full thickness biopsy to full depth of detrusor muscle
§ Resect all visible disease to muscle and margin
§ After first resection -scarring thickens bladder make second resection safer
○ Allows best T-staging
§ Approx 30% of apparent T1 tumours understated by TURBT
□ Repeat 4-6 weeks to assess recurrence for all >=T1 and high grade Ta, even if initial resection thought to be complete
○ Cyto-reduction is important before trimodality therapy- Hydronephrosis management options:
§ Patients with VUJ obstruction should have stenting performed prior to treatment commencement
○ Stenting
§ Plastic, silicone, reinforced. Can be solid
□ Works by urine tracking along outside of stent (hard stent vs soft tissue), unless cancer surrounds stent and hardens.
® Reinforced stents are harder (cancer takes longer to het as hard)
□ Changed between 3-12months -get brittle and encrusted (stones)
® Inability to remove
§ Stent colic pain ?from distention or muscle spasm
® Treat with alpha blockers/cholinergics/NSAID to relax muscle
® Hurts when urinate -urine refluxes up ureter
§ Stent bleeding -expected from stent
□ Rubs/irritates urothelium in renal pelvis/bladder
□ Esp clopidogrel causing clot retention
§ Does not seed tumour
○ Perc nephrostomy (bridge to treatment, not good palliation as frequent admission)
○ Reimplantation nephrectomy (doesn’t work post RT)
○ Observation - Consider maintenance of Hb > 100g/L (if concurrent chemoRT)
- Recommend smoking cessation (increases risk of progression and recurrence)
- Hydronephrosis management options:
Discuss management options for muscle invasive bladder cancer.
- Radical cystectomy remains the gold-standard therapy (traditionally the cornerstone of curative treatment removal of bladder, prostate, seminal vesicles, pelvic lymph node dissection and reconstruction of the urinary tract)
○ No randomised trial to suggest otherwise
○ Radical cystectomy is associated with significant perioperative mortality and morbidity risk
○ Open or laparoscopic- Trimodality therapy is a reasonable alternative (bladder preservation approach with maximal TURBT followed by chemoRT)
○ Comparative cure rates are similar (in carefully selected cohorts)
§ No direct RCTs comparing RC vs. BCT
§ TMT tends to be reserved for pt not fit for surgery
○ 5 yr OS 50%, bladder preservation rate 70%
§ Main modality of failure is distant (up to 80%)
§ ~67% cCR after induction
○ Toxicity and QoL implications are generally better
§ More tolerable for elderly or medically co-morbid patientsD
- Trimodality therapy is a reasonable alternative (bladder preservation approach with maximal TURBT followed by chemoRT)
Discuss cystectomy for bladder cancer.
Cystectomy
- Remains the standard of care for patients fit for extensive surgery for MIBC (cT2-T4a) with: - Neoadjuvant platinum-based chemotherapy is also the standard of care ○ Neoadjuvant preferred as pt frail postop. ○ Metanalysis: 5% improved overall survival ○ 3x MVAC protocol (MTX, vinblastine, doxorubicin, cisplatin) § ECOG 0-1, Cr clearance >60, good hearing/peripheral nerves, no heart failure § Given dose dense 2 weekly with growth factor support ○ Alternative Cisplatin+gemcitabine (v slightly worse outcome but better tolerated) - Neoadjuvant immuno -ongoing RCT trial
Cystectomy:
- Preferred: (also see candidates for tri-modality)
○ Widespread CIS
○ Multifocality
○ Residual/recurrent disease following TUBRT
○ Poor baseline function
○ Relative contraindications to chemo/radiotherapy
○ Variant pathology
○ Location
○ Ureter involvement
○ Acceptability of stoma
- Also excellent local palliation
- Vs partial cystectomy
○ Want radical cystectomy but unfit, or for organ preservation
○ Partial cystectomy probably good enough control of solitary MIBC, not near trigone (eg. Near urachus)
- The procedure entails: ○ As soon after recovery from NAC as possible ○ Open or minimally invasive ○ Resection of bladder and adjacent organs en-bloc § Prostatectomy/SV/vas/proximal urethra § If required: Hysterectomy + 1/3 vagina +- BSO ○ Bilateral pelvic lymphadenectomy if M0 § At minimum EI, II, obturators § More nodes = better outcomes, at least 10 ○ Formation of: § 90% Abdominal stoma (continent or incontinent) □ Ileal conduit 15cm § Or Neobladder (sbowel connected to urethra) 50cm of ileum - □ For young nonsmokers, Not for multifocal disease □ 30% work well, 60% poor quality of life -incontinence, self IDC, mucus washout, frequency ○ 30% of patients experience complications within 3 months of surgery § Sexual dysfunction § Nocturnal incontinence § Urinary retention § Serious complications in 3-5% (urethro-enteric anastomotic stricture, intestinal obstruction) □ Ileus, dehiscence, infection, lymph leak, urine leak. 2-3 weeks in hospital § Perioperative mortality is 2-5%, 1-2% for well selected younger patients ○ Late □ Recurrent urosepsis □ Hernia, ueteroileal stricture, stoma issues, □ SBO □ Lymphocele □ 35% develop CKD3 - Open vs. Minimally invasive/ Robotic ○ Less invasive, less blood loss, faster recovery ○ Most benefitial in frail, elderly, obese ○ Reduction in ureter/hernia complications ○ Can have sexual function preserved ○ Good QoL
Role of bladder preservation chemo/radiotherapy
- Selection
- Tumour: T2/3a, <5cm, CIS, unifocal
- Patient: nil hydro (understaging) good bladder and renal function , ECOG
- Treatment max TURBT
- Outcomes
○ 5yr OF 50%, bladder preservation 66%
○ 30% G3/4 acute tox, 5% late tox
Recurrence after CR: 30% CIS, 15% invasive, 15% N=
Partial cystectomy = indications
- Major: indications for radical, but unfit for radical cystectomy on physiologiocal grounds
- Minor/weak: localised solitary, urachal, partial preference, location - technically easier if distant from UO/bladder neck, diverticulum tumour
Discuss adjuvant management after cystectomy for bladder cancer.
- Consider adjuvant chemo if NAC was not given in pT3+ or N+ (generally pts not fit, poor renal function)
○ EORTC 30994
○ 5yr PFS benefit (48 >32%) without improvement in OS (54 >48%)
○ Chemo included Gemcitabine/Cisplatin, MVAC, or ddMVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)- Adjuvant Radiotherapy (limited use)
○ Consider adjuvant chemo or PORT for pT3-pT4a, SM+, ECE, or < 10 LN removed.
○ pT3-4, SM+ or ECE: Pelvic nodes to 45-50.4 Gy and cystectomy bed (if SM+) to 54-60 Gy.
○ LR after RC: 45-50 Gy to pelvic nodes, 60-65 Gy to gross LR with CDDP. - Adjuvant Nivolumab -not on PBS
○ Persistent muscle invasive after neoadjuvant chemo, or high risk features or no chemo
RCT CHECKMATE: HR 0.7 (15% absolute) Improved DFS, especially >1% PDL.
- Adjuvant Radiotherapy (limited use)
Describe management of non-muscle invasive bladder cancer.
Non-MIBC (Ta, Tis, T1) - 75% of all bladder Ca
- All should have cystoscopy with a TURBT in the first instance - Further therapy is based on the pathology and risk grouping - risk calculator Essentially add adjuvant intravesical BCG unless low grade papillary (single chemo)
Radiotherapy +/- chemotherapy
- Can be used in NMIBC, generally multiple TURBT but poor bladder function so limited role of RT
○ Concern re understaged NMIBC
- Retrospective study (Weiss, J Clin Onc 2006); 141 pt T1, 60% HG, (RT=28, RT+ chemo=113) ○ cCR 88% ○ Rates of tumour progression 5 yr 19%, 10yr 30% ○ CSS 5yr 82%, 10yr 73% ○ 80% bladder preservation
NMIBC Pembrolizumab post TURBT (not on PBS)
Discuss the side effects for bladder RT.
Acute:
-Fatigue
-Irritative or obstructive urinary symptoms - Bladder spasms, dysuria, nocturia, frequency, incontinence, urgency, retention.
-Proctitis - Including diarrhoea, increased bowel frequency, rectal urgency, pain and bleeding.
-Toxicity relating to chemotherapy
-Sexual function - female Vaginitis, vaginal mucositis, dyspareunia/stenosis.
-Sexual function - male Sexual and erectile dysfunction.
Late:
-Fatigue
-Cystitis/urethritis - Includes haematuria.
-Bladder dysfunction - New or ongoing.
-Urinary incontinence
-Radiation induced small bowel obstruction - Rare.
-Proctitis
-Faecal incontinence
-Radiation induced rectourethral fistulas - Rare.
-Lymphoedema
-Sexual dysfunction - male Including erectile dysfunction, impotence, dry and/or painful ejaculation, haematospermia and reduction in ejaculate. Patients should be offered sexual counselling to manage potential late effects related to sexual function.
-Sexual dysfunction - female Including dyspareunia, vaginal dryness and vaginal stenosis.
-Premature ovarian failure/menopause - If ovaries present.
-Impaired fertility or infertility Fertility preservation should be discussed prior to commencement of treatment.
-Second malignancy
- Pooled RTOG analysis [Efstathiou JCO ‘09]: Late effects of bladder preservation do not appear prohibitive.
No radical cystectomies were performed due to late treatment-related toxicity.
○ 285 pts. RTOG 8903, 9506, 9706, 9906.
○ 5y late G2 10% (9.6% GU, 1.9% GI).
○ 5y late G3 7% (5.7% GU, 1.9% GI). No G4 events, no pts req’d RC due to treatment related toxicity.
§ Median duration of late G3 pelvic toxicity of 7.1 months. Time to late G3 of ~2 years. - Quality of life [Zietman JoU ‘03]: Normal bladder fxn preserved in most pts w ~20% having persistent bowel sx.
○ 71 pts alive and w native bladders. 49 pts participated, but only 31 came in for urodynamic study. Median f/u 6.3y.
○ Of those that did UDS, 24/32 (75%) with normally functioning bladders.
§ Decreased compliance in 7 pts (22%).
§ Bladder HSN, involuntary detrusor contractions and incontinence in 2 women.
○ > 85% no bothersome urinary symptoms.
§ 6% flow sx, 15% urgency, and 19% control problems.
○ Bowel sx in 22% (e.g. rectal urgency), with 14% recording any level of distress.
○ 50% normal erectile function. - BC 2001, James et al
Acute G3-4 36% (21% GU, 10% GI), late G3-4 ~5% with CCRT.
Describe the radiation technique for adjuvant/recurrent bladder cancer.
Adjuvant (NRG-GU001)
Patients
Post cystectomy; consider chemo or PORT
pT3-pT4a, SM+, ECE, or < 10 LN
Pre-simulation
MDT discussion
Simulation
Fusion
Dose prescription
pT3-4, SM+ or ECE:
* Pelvic nodes 45-50.4 Gy
* cystectomy bed (if SM+) 54-60 Gy.
LR after RC:
* 45-50Gy to pelvic nodes
* 60-65Gy to gross LR
* with CDDP
Volumes
○ CTV_50.4:
§ PLN only if SM-, include cystectomy bed if SM+.
○ CTVn_50.4:
§ Presacrals (1-1.5 cm anterior to sacrum), bilateral distal common iliac, EI, II, obturators.
§ Extends from top of L5-S1 to top of S3.
○ CTVp_50.4 (SM+ only):
§ Ant: mid-plane of pubis above pubis, posterior plane of pubis below pubis.
§ Post: abut anterior 1/3 of rectum without extending into rectum.
§ Sup: 2 cm sup to pubic symphysis.
§ Inf: Stop 2-3 mm above penile bulb, or 1 cm below lower pole of obturator foramen.
○ PTV 0.5-0.7 cm expansion.
Target Verification
OARs
Bowel bag V40 < 30% (50%), Rectum V45 < 70% (80%). Bowel bag contoured 3 cm above L5-S1.
