NCCN Bladder 6.2020 Flashcards
INITIAL EVALUATION
Suspicious bladder mass
H and PE Office cystoscopy Consider cytology Abdominal and pelvic imaging with upper tract collecting system BEFORE TURBT Smoking screening
BL-1
PRIMARY EVALUATION and SURGICAL TREATMENT
Bladder mass
EUA/bimanual exam
TURBT
Single-dose intravesical chemotherapy within 24 hours of TURBT: Gemcitabine (preferred, cat 1) or mitomycin (cat 1)
Sessile or suspicious for high grade or Tis: selected mapping biopsies
Upper tract imaging if not yet done
BL-1
Initial workup for muscle-invasive bladder CA
CBC
Chemistry profile, with ALK PHOS
Chest imaging
Bone imaging, if suspicious/symptomatic
BL-1
Thanos FAQ!
“Sige, immediate intravesical chemotherapy reduces the ________ by ________ %.”
Immediate intravesical chemotherapy reduces 5-year RECURRENCE (rekerens) rate by 35 %, and has a NNT to prevent recurrence of 7.
Does NOT reduce risk of progression or mortality.
BL-1 footnote, BL-F
SECONDARY SURGICAL TREATMENT/ADJUVANT INTRAVESICAL TREATMENT
cTa, low grade
Observation
OR
Intravesical therapy
BL-2
SECONDARY SURGICAL TREATMENT/ADJUVANT INTRAVESICAL TREATMENT
cTa, high grade
Repeat TURBT if:
- Incomplete resection
- No muscle in specimen
Then: BCG (preferred) OR Intravesical chemotherapy OR Observation
If BCG given –> give maintenance BCG (preferred)
BL-2
SECONDARY SURGICAL TREATMENT
cT1
Strongly advise repeat TURBT
OR
Consider cystectomy if high-grade
BL-2
ADJUVANT INTRAVESICAL TREATMENT
cT1
Repeat TURBT: (+) residual disease
BCG (cat 1)
OR
Cystectomy
If BCG given –> give maintenance BCG (preferred)
BL-2
ADJUVANT INTRAVESICAL TREATMENT
cT1
Repeat TURBT: (-) residual disease
BCG (cat 1) OR Intravesical chemotherapy OR Observation in highly selected cases: low grade, limited lamina propria invasion, no CIS
If BCG given –> give maintenance BCG (preferred)
BL-2
ADJUVANT INTRAVESICAL TREATMENT
Tis
BCG
BL-2
Evaluation and Treatment
Posttreatment cTa, T1, Tis recurrent or persistent
Cystoscopy: positive
TURBT
Single-dose intravesical chemotherapy within 24 hours of TURBT: gemcitabine (cat 1) or mitomycin (preferred, cat 1)
Based on tumor grade and stage: Adjuvant intravesical therapy OR Cystectomy OR Pembrolizumab
BL-3
Pembrolizumab is indicated for ________.
Pembrolizumab is indicated for treatment of patients with:
BCG-unresponsive high-risk, NMIBC with Tis or without papillary tumors
BL-3, footnote
Valrubicin is approved for ________.
Valrubicin is approved for BCG-refractory carcinoma in situ.
BL-3, footnote
Evaluation and Treatment
Posttreatment cTa, T1, Tis recurrent or persistent
Cystoscopy: suspicious for recurrence post-intravesical therapy (no more than 2 cycles)
TURBT
Single-dose intravesical chemotherapy within 24 hours of TURBT: gemcitabine (cat 1) or mitomycin (preferred, cat 1)
TURBT result:
- No residual disease: maintenance BCG (preferred)
- cTa, cT1, Tis: cystectomy (preferred for cT1 OR pembrolizumab (select patients) or change intravesical agent (consider)
- T2 or higher: RESTAGE and manage accordingly
BL-3
Evaluation and Treatment
Cytology: positive
Imaging: negative
Cytoscopy: negative
Selected mapping biopsies including transurethral prostate biopsy AND Upper tract cytology AND Consider URS AND Enhanced cystoscopy (if available)
BL-4
Treatment
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: bladder, prostate, upper tract negative
Follow-up at 3 mo, then at longer intervals
OR
If prior BCG, maintenance BCG (optional)
BL-4
Treatment
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: bladder positive
BCG, then:
If no evidence of disease (NED): maintenance BCG (preferred)
If persistent r recurrent disease:
Cystectomy OR pembrolizumab (select pxs) OR change intravesical agent (if incomplete response, cystectomy OR pembrolizumab)
If BCG-unresponsive:
Cystectomy OR pembrolizumab (in select patients)
BL-4
WORKUP
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: prostate positive
Urothelial CA of the Prostate!
DRE Cystoscopy (with bladder biopsy) TUR biopsy of prostate to include stroma PSA Needle biopsy if DRE is abnormal (in selecte patients) Imaging of upper tract collecting system
PRIMARY TREATMENT
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: prostate positive: MUCOSAL prostatic urethra
TURP and BCG
If on ffup imaging: local recurrence, then cystoprostatectomy + urethrectomy
UCP-1
PRIMARY TREATMENT
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: prostate positive: ductal + acini
CXR + abdominal/pelvic CT
Cystoprostatectomy + urethrectomy
OR
TURP and BCG, then if on ffup imaging: local recurrence, then cystoprostatectomy + urethrectomy
UCP-1
PRIMARY TREATMENT
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: prostate positive: stromal invasion
CXR + abdominal/pelvic CT
Cystoprostatectomy + urethrectomy + neoadjuvant chemotherapy
then consider adjuvant chemotherapy (if neoadjuvant not given)
UCP-1
PRIMARY TREATMENT
Cytology: positive
Imaging: negative
Cytoscopy: negative
After workup: prostate positive: metastatic
Systemic therapy
UCP-1
PRIMARY TREATMENT and ADJUVANT TREATMENT
Stage II, cystectomy candidates
Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy (cat 1)
OR
Neoadjuvant cisplatin-based combination chemotherapy followed by partial cystectomy (highly selected patients with solitary lesion in a suitable location, no Tis)
OR
Cystectomy alone for those not eligible to receive cisplatin-based chemotherapy
OR
Concurrent chemoradiotherapy (cat 1) then reassess after 2-3 mos –> no tumor: observe;
–> tumor: Tis Ta T1: intravesical BCG OR surgical consolidation OR treat as metastatic
BL-5
PRIMARY TREATMENT and ADJUVANT TREATMENT
Stage II, NON-cystectomy candidates
Concurrent chemoradiotherapy (cat 1, preferred)
OR
RT
OR TURBT
Then reassess after 2-3 mos –> no tumor: observe;
–> tumor: Systemic therapy OR concurrent chemoRT or RT alone if no prior RT or TURBT and best supportive care
BL-6
PRIMARY TREATMENT ADJUVANT TREATMENT
Stage IIIA, cystectomy candidates
Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy (cat 1)
OR
Cystectomy alone for those not eligible to receive cisplatin-based chemotherapy
OR
Concurrent chemoradiotherapy (cat 1) then reassess after 2-3 mos –> no tumor: observe;
–> tumor: Tis Ta T1: intravesical BCG OR surgical consolidation OR treat as metastatic
BL-7
PRIMARY TREATMENT and ADJUVANT TREATMENT
Stage IIIA, NON-cystectomy candidates
Concurrent chemoradiotherapy (cat 1) then reassess after 2-3 mos;
- no tumor: observe;
- tumor: systemic therapy OR TURBT OR best supportive care
OR
RT
BL-7
Optimal candidates for bladder preservation with chemoRT:
Patients with tumors WITHOUT hydronephrosis
NO concurrent or extensive Tis
< 6 cm
Tumors should allow visually complete or maximally debulking TURBT
BL-7
ADJUVANT TREATMENT
Stage IIIA, cystectomy candidates
Based on pathologic risk (pT3-T4 or positive nodes or positive margins:
Consider adjuvant cisplatin-based chemotherapy or adjuvant RT (cat 2B) if no neoadjuvant given
BL-7
PRIMARY TREATMENT
Stage IIIB, downstaging systemic therapy option
Downstaging systemic therapy, then reassess tumor status 2-3 mo after treatment
Complete response: Consolidation cystectomy OR consolidation chemoRT OR observation
Partial response: Cystectomy OR chemoRT OR treat as metastatic
Progression: treat as metastatic
BL-8
PRIMARY TREATMENT
Stage IIIB, concurrent chemoradiotherapy
Reassess tumor status 2-3 mo after treatment
Complete response: ffup algorithm
Partial response: Tis, Ta, T1 consider intravesical BCG OR surgical consolidation OR treat as metastatic
Progression: treat as metastatic disease
BL-8
PRIMARY TREATMENT
Stage IVA, M0
Systemic therapy –> 2-3 cycles, reassess with cystoscopy, EUA, TURBT, and imaging of abd/pelvis
OR
Concurrent chemoRT, then reassess after 2-3 months
- No tumor: consolidation systemic therapy OR chemoradiotherapy (if no previous RT) and/or cystectomy
- Tumor present: systemic therapy OR chemoRT (if no previous RT) and/or cystectomy
BL-9
PRIMARY TREATMENT
Stage IVA, M1a disease
Systemic therapy, then evaluate with cystoscopy, EUA, TURBT, and imaging of abd/pelvis
If CR: Concurrent chemoRT OR cystectomy
Stable disease or progression: treat as metastatic
BL-9
WORKUP and PRIMARY TREATMENT
Metastatic Stage IVB
Bone scan Chest CT Consider CNS imaging GFR scan, to assess cisplatin eligibility Consider biopsy if feasible Molecular/genomic testing
Systemic therapy
AND/OR
Palliative RT
BL-10
TREATMENT
Local recurrence or persistent disasese;
Preserved bladder
Muscle-invasive
Cystectomy OR ChemoRT (if no prior RT) OR Systemic therapy OR Palliative TURBT and best supportive care
BL-11
TREATMENT
Local recurrence or persistent disasese;
Preserved bladder
Tis, Ta, or T1
Consider intravesical therapy --> if no response --> cystectomy OR Cystectomy OR TURBT
BL-11
TREATMENT
Cytology: positive
Preserved bladder
Cystoscopy, EUA, selected mapping biopsy: negative
Retrograde selective washings of the upper tract
Prostatic urethral biopsy
Upper tract positive –> UTUC
Prostate positive –> UCP
BL-11
TREATMENT
Metastatic or local recurrence postcystectomy
Systemic therapy OR ChemoRT (if no previous RT) OR RT
BL-11
TURBT: muscle may be omitted in _________.
Documented low-grade Ta disease
BL-B
TURBT: suspected or known CIS:
Biopsy adjacent to papillary tumor
Consider prostate urethral biopsy
BL-B
TURBT: Papillary appearing tumor (likely NMIBC) - repeat TURBT after 6 weeks if:
Incomplete resection
No muscle in original specimen for high-grade
Large (>= 3 cm) or multi-focal lesions
Any T1 lesion
BL-B
TURBT: Sessile/flat or invasive appearing tumor (likely MIBC), repeat TURBT if:
No muscle in original specimen for high-grade
Any T1 lesion
First resection does not allow adequate staging for treatment selection
Incomplete resection and considering tri-modality bladder preservation therapy
BL-B
Maximal TURBT + concurrent chemoRT is most suitable for patients with:
Solitary tumors Negative nodes No CIS No tumor-related hydronephrosis Good pretreatment bladder function
BL-B
Regional lymphadenectomy recommended for:
High-grade upper GU tract tumors
BL-B
Regional lymphadenectomy for:
Left-sided renal pelvic, upper ureteral, and midureteral tumors
Paraaortic LNs from renal hilum to aortic bifurcation
Midureteral tumor: include common iliac, external iliac, obturator, hypogastric LNs
BL-B
Regional lymphadenectomy for:
Right-sided renal pelvic, upper ureteral, and midureteral tumors
Paracaval LNs from renal hilum to IVC bifurcation
Midureteral tumor: include common iliac, external iliac, obturator, hypogastric LNs
BL-B
Regional lymphadenectomy for:
Distal ureteral tumors
Common iliac
External iliac
Obturator
Hypogastric LNs
BL-B
Pelvic Exenteration (cat 2B)
For recurrence in female patients with >= T2 primary carcinoma of the urethra
Ilioinguinal lymphadenectomy and/or chemoRT for >=T3
BL-B
TURP is the primary treatment option for:
Urothelial carcinoma of the prostate with ductal/acini or prostatic urethral pathology.
Postsurgical intravesical BCG recommended.
BL-B
TUR of urethral tumor is the primary treatment for:
Tis, Ta, and T1 primary carcinoma of the urethra.
Consider postsurgical intraurethral therapy
BL-B
Partial cystectomy indications
cT2 muscle-invasive disease with solitary lesion amenable to resection with adequate margins Select situations (including cancer in bladder diverticulum) No CIS as determined by random biopsies
Give: neoadjuvant cisplatin-based chemotherapy
Bilateral pelvic lymphadenectomy: common iliac, internal and external iliac, obturator nodes
BL-B
Radical nephrouretectomy with bladder cuff is the primary treatment for:
Non-metastatic high-grade upper GU tract tumors (UTUC)
Consider single-dose immediate postop intravesical chemotherapy (decrease in intravesical recurrence)
Neoadjuvant chemotherapy: consider in high-grade disease
BL-B
Favorable criteria for nephron preservation in UTUC
Low-grade tumor based on cytology and biopsy
Papillary architecture
Tumor size <1.5 cm
Unifocal tumor
Cross-sectional imaging showing no concern for invasive disease
BL-B
Less favorable criteria for nephron preservation in UTUC
Multifocal tumors Flat or sessile tumor architecture Tumor size > 1.5 cm High-grade tumors cT2-T4 Mid and proximal tumor due to technical challenges Tumor crossing the infundibulum or UPJ
BL-B
Imperative indications for conservative therapy of UTUC
Bilateral renal pelvis and/or urothelial carcinoma of the ureter
Solitary or solitary functioning kidney
Chronic kidney disease/renal insufficiency
Hereditary predisposition (HNPCC)
BL-B
Mixed histology urothelial cancer should be treated in a similar manner to:
Pure urothelial carcinoma
BL-D
Pure squamous cell carcinoma of the bladder
No proven role for neoadjuvant chemotherapy
Local control with surgery + RT recommended
Clinical trial for advanced disease
Paclitaxel + ifosfamide + cisplatin for selected patients
Postoperative RT for positive margins
Best supportive care
BL-D
Pure adenocarcinoma including urachal, localized disease
No proven role for neoadjuvant chemotherapy
Local control with surgery + RT recommended
Urachal with localized disease:
Partial or complete cystectomy with en bloc resection of the urachal ligament with umbilicus and LN dissection
Best supportive care
BL-D
Pure adenocarcinoma including urachal, node-positive and advanced disease
FOLFOX: oxaliplatin, leucovorin, and 5-FU
or
GemFLP: 5-FU, leucovorin, gemcitabine, and cisplatin
BL-D
Treatment for any small-cell component
Concurrent chemoRT or neoadjuvant chemotherapy followed by local treatment (cystectomy or radiotherapy)
Neoadjuvant chemotherapy:
Etoposide + cisplatin
Ifosfamide + doxorubicin with etoposide + cisplatin
If cisplatin ineligible:
etoposide + carboplatin
BL-D
AUA Risk Stratification for NMIBC:
Low Risk
Low grade solitary
Papillary urothelial neoplasm of LMP
BL-E
AUA Risk Stratification for NMIBC:
Intermediate Risk
Recurrence within 1 year, LG Ta Solitary LG Ta > 3 cm LG Ta, multifocal High grade (HG) Ta, =< 3 cm LG T1
BL-E
AUA Risk Stratification for NMIBC:
High Risk
HG T1 Any recurrent, HG Ta HG Ta, > 3 cm or multifocal Any CIS Any BCG failure in HG patient Any variant histology Any lymphovascular invasion Any HG prostatic urethra involvement
BL-E
FOLLOW-UP
Low-Risk, NMIBC
Cystoscopy: 3 and 12 mo, then annually
Upper tract and abdominal/pelvic imaging: baseline imaging, then annually as clinically indicated
BL-E
FOLLOW-UP
Intermediate Risk, NMIBC
Cystoscopy: 3, 6, 12 mo, then every 6 mo for year 2, then annually for years 3-5
Upper tract and abdominal/pelvic imaging: baseline imaging in year 1, then as indicated
Urine cytology: 3, 6, 12 in year 1, urine cytology every 6 mo in year 2, then annually until year 5
BL-E
FOLLOW-UP
High Risk, NMIBC
Cystoscopy: every 3 mo in years 1-2, every 6 mo in years 3-5, then annually
UT imaging: baseline imaging in year 1, then every 1-2 y
Abdominal/pelvic imaging: baseline at year 1, then as indicated
BL-E
FOLLOW-UP
Postcystectomy NMIBC: cystoscopy schedule
Wala na siyang bladder! 😢
FOLLOW-UP
Postcystectomy NMIBC
CTU or MRU at 3 and 12 mo in year 1, then annually until year 5, then US annually
Renal function tests, LFTs, CBC, CMP, B12 every 3-6 mo if received chemo in year 1, then annually
Urine cytology and urethral wash cytology every 6-12 mo until year 2, then as indicated
BL-E
FOLLOW-UP
Postcystectomy muscle invasive BC
CTU or MRU, CXR or chest CT every 3-6 mo until year 2, then annually until year 5, then renal US annually
FDG PET/CT (cat 2b) if suspected metastatic disease
Renal function tests, LFTs, CBC, CMP, B12 every 3-6 mo if received chemo in year 1, then annually
Urine cytology and urethral wash cytology every 6-12 mo until year 2, then as indicated
BL-E
FOLLOW-UP
Post-bladder sparing (partial cystectomy or chemoRT)
Cystoscopy: every 3 mo in years 1-2, then every 6 mo in years 3-4, then annually years 5-10
Imaging: CTU or MRU, CXR or chest CT every 3-6 mo in years 1-2
FDG PET/CT if mets suspected
Renal function tests, LFTs, CBC, CMP, B12 every 3-6 mo if received chemo in year 1, then annually
Urine cytology every 6-12 mo in years 1-2, then as indicated
BL-E
Immediate postoperative intravesical chemotherapy timing:
Single instillation within 24 hours of surgery (ideally 6 hours)
BL-F
Immediate intravesical agents
Gemcitabine (preferred due to better tolerability) (cat 1)
Mitomycin (cat 1)
NOT effective: thiotepa
BL-F
Immediate postoperative intravesical chemotherapy NOT effective in:
Patients with elevated EORTC recurrence risk score >= 5, includes patients with >= 8 tumors and those with >= recurrence per year.
BL-F
Immediate postoperative intravesical chemotherapy contraindications:
Bladder perforation
Known drug allergy
BL-F
Induction (adjuvant) intravesical chemo or BCG is a treatment option for:
NMIBC
BL-F
In the event of a BCG shortage, prioritize induction of:
High-risk patients (high-grade T1 and CIS)
BL-F
In the event of a BCG shortage, multiple patients may be treated by:
splitting the dose of BCG (1/2 or 1/3)
BL-F
Induction intravesical chemotherapy or BCG timing:
Start: 3-4 weeks after TURBT with or without maintenance
Weekly for 6 weeks, maximum of 2 consecutive cycle inductions without complete response
BL-F
BCG contraindications:
Traumatic catheterization Bacteriuria Persistent gross hematuria Persistent severe local symptoms Systemic symptoms
BL-F
Maintenance intravesical BCG SWOG regimen
6-week induction course, then maintenace with 3 weekly instillations at months 3, 6, 12, 18, 24, 30, and 36.
BL-F
What does “sessile” mean? 😅
Sessile means “flat”, as opposed to papillary which is pedunculated. Flat tumors are more likely to be CIS or invasive.
Perioperative chemotherapy (neoadjuvant or adjuvant)
Preferred:
DDMVAC + growth factor suppport x 3-4 cycles
Gemcitabine and cisplatin x 4 cycles (21 days preferred)
Other:
CMV (cisplatin, methotrexate, and vinblastine) x 3 cycles
BL-G
What does DDMVAC mean?
Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin
BL-G
First-line systemic therapy for locally advanced or metastatic disease (Stage IV)
Cisplatin eligible
Gemcitabine and cisplatin (cat 1) followed by avelumab maintenance therapy
DDMVAC with growth factor support (cat 1) followed by avelumab maintenance therapy
BL-G
First-line systemic therapy for locally advanced or metastatic disease (Stage IV)
Cisplatin INeligible
Preferred:
Gemcitabine and carboplatin followed by avelumab maintenance therapy
Atezolizumab or Pembrolizumab ONLY for PD-L1 expressing tumors
BL-G
Second-line systemic therapy for stage IV, post-PLATINUM
Preferred:
Pembrolizumab (cat 1)
Alternative preferred: Atezolizumab Nivolumab Durvalumab Avelumab Erdafitinib
BL-G
Second-line systemic therapy for stage IV, post-CHECKPOINT INHIBITOR
Preferred for cisplatin ineligible, chemo naive:
Gemcitabine/carboplatin
Cisplatin eligibile:
Gemcitabine/cisplatin
DDMVAC with GF support
BL-G
Subsequent-line systemic therapy for stage IV
Preferred:
Enfortumab vedotin 🧐
Erdafitinib
BL-G
Radiosensitizing chemotherapy regimens for organ-preserving chemoradiation
Preferred: Cisplatin and 5-FU Cisplatin and paclitaxel 5-FU and mitomycin Cisplatin alone
BL-G
Bladder
T1
Invades the lamina propria (subepithelial connective tissue)
ST-1
Bladder
T2a
T2b
Invades the superficial (T2a) and deep (T2b) muscularis propria
ST-1
T3a
T3b
Invades perivesical tissue microscopically (T3a) or macroscopically (T3b)
ST-1
T4a
T4b
Extravesical tumor directly invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall
ST-1
Bladder
N1
Single regional LN metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral LN)
ST-1
Bladder
N2
Multiple regional LN metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral LN)
ST-1
Bladder
N3
Lymph node metastasis to the common iliac LN
ST-1
Bladder
M1a
Distant metastasis limited to LNs beyond the common iliacs
ST-1
Bladder
M1b
Non-LN distant metastases
ST-1
UTUC
T1
Subepithelial connective tissue
ST-1
Adjuvant intravesical chemotherapy
Alternatives to BCG
Mitomycin or gemcitabine Epirubicin Valrubicin Docetaxel Sequential gemcitabine/docetaxel or gemcitabine/mitomycin
Split dose BCG: 1/3 or 1/2 dose
BL-F
Adjuvant intravesical chemotherapy
Timing
Start: 3-4 weeks after TURBT with or without maintenance x weekly dose for 6 weeks
Maximum 2 cycles w/o complete response
BL-F
Adjuvant/maintenance intravesical chemotherapy
Contraindications to BCG
Traumatic catheterization Bacteriuria Persistent gross hematuria Persistent severe local symptoms Systemic symptoms
BL-F
Immediate postop intravesical chemotherapy
Dose and Timing
Details
Contraindications
Single dose of gemcitabine or mitomycin within 24 hours (ideally within 6 hours)
Reduces recurrence by 35%
NNT to prevent recurrence of 7
NOT effective in: EORTC >= 5, >=8 tumors, >=1 recurrence per year
Contraindications to gemcitabine/mitomycin: Drug allergy, bladder perforation
Maintenance intravesical BCG
SWOG regimen
6-week induction course of BCG
then
Maintenance: 3 weekly instillations at months 3, 6, 12, 18, 24, 30, 36
Intermediate risk: given for 1 year
High-risk: given for 3 years
