La terapia neo-adiuvante

nei tumori infiltranti endovescicali

IV°Meeting Uro-Oncologico UP DATE 2016 SUI TUMORI UROLOGICI

Prof. Andrea B. Galosi

Direttore Clinica Urologia

Ospedali Riuniti Ancona - UNIVPM

Tumore della vescica

CYSTECTOMY FOR BLADDER CANCER

FAILURE AFTER LOCAL

TREATMENT < T2

MUSCLE INVASIVE

EARLY

MUSCLE INVASIVE LATE STAGE T3-T4a +/- Hydronephrosis

SALVAGE CYSTECTOMY

(QUALITY OF LIFE & UNTREATABLE

RELATED COMPLICATIONS)

Guidelines recommend administration of Neoadjuvant cisplatin-based Chemotherapy in patients who have cT2–T4a N0/N1

5yrs OS improvement (+7%)

Despite Guidelines recommendations

• NAC is largely under-utilised:– only 15% receiving neoadjuvant chemo in recent years

• Reasons– Multiple baseline comorbidities

• cardiac and renal dysfunction

– Advanced age at disease presentation

– Urologist concerns • Increased risk of perioperative morbidity and mortality (8%)

– Oncologist concerns• Morbidity and mortality during CHT

– Lack of Multidisciplinary approach

NeoAdjuvant Chemotherapy (NAC) for B.Cancer

The Effect of Neoadjuvant Chemotherapy on Perioperative Outcomes in Patients Who Have Bladder Cancer Treated with Radical Cystectomy: A

Population-based Study

Gandaglia G et al. Eur. Urology 2014

Surveillance Epidemiology End Results database

3760 pts (2000-2009) were evaluate retrospectively, mean age 75

416 (11.1%) received neoadjuvant chemotherapy

30-d 90-d

• Complication 66.0% 72.5%

• Readmission 32.2% 46.6%

• Mortality 5.3% 8.2%

• Neoadjuvant chemotherapy was not associated with higher risk of 30-and 90-d complications

Eur Urol (2014), http:// dx.doi.org/10.1016/j.eururo.2014.01.014

Ancona-Fermo Experience (2012-2016)

74 patients with MIBC

– 30 (40,5%) NAC + SURGERY

– 43 (59,5%) IMMEDIATE SURGERY

• Post-operative Adjuvant CHT in 3 pts

Multidisciplinary evaluation (Onco-Urol-Pathol)

Pathology based on TUR in all cases

NAC in cT2-T4a N0-1, if good renal function

Methods: NeoAdjuvantChemotherapy

1. Baseline chest-abdominal CT

2. Imaging after 2-3 cycles US or CT

3. If response, futhrer 2-3 cycles were added(80%)

4. Re-staging after completed NAC

5. Wash-out/recovery after NAC (3 weeks)

6. Surgery

PATIENTS CHARACTERISTICS

CYST. (44) NAC+CYST. (30)AGE 76 (54-88) 69 (50-84)AGE > 79yrs 25(33,8%) 6 (20%)Co-Morbidity >1 38/44 12/30ASA SCORE ≥3 30/44 15/30Hydrophrosis 20/44 9/30Nephrostomy 14/44 9/30Squamos diff. 4/44 6/30≤ T2a 33/44 3/30cT2b-T3 11/44 18/30cT4 – N1 0 9/30

Timing of NAC after Diagnosis of Invasive BC

Time to NAC (weeks)

• From Decision based on pTcNM (Tur &completed staging) to starting NAC– < 1 w (range, 0.2-2 w)

• From TransUrethral Resection to starting NAC– 3.6 w (range 3-7.5 wks)

NeoAdjuvant Chemotherapy (NAC)

• 26 pts: Gemcitibine and Cisplatin (GC)

– Gemcitabine 1000mg/m2 on Days 1, 8, and 15

– Cisplatin 75 mg/m2 on Day 2

– Cycles repeated every 28 days for 3 cycles

– Mean 4 cycles (range 3-6)

• 3 pt (IRC): weekly Gemcitabine 700mg/m2 + Cis 50mg/m2, 3 cycles

• 1 pt (84yrs): weekly Paclitaxel 75 mg/mq, 4 cycles

• Ancillary procedures– 3 pt Bilateral hydronephrosis: Nephrostomy + stent– 6 pts Monolateral hydronephr.: Nephrostomy– 2 times Nephrostomy displacement– Placement of filter in the v. cava before surgery

• 4 Deep Venous Trombosis detectet at re-staging CT– 2 asymptomatic Pulmonary Embolism

• 3 Infection (2 UTI, 1 Respiratory)• 2 Mild worseing renal funcion, reversable (1.7, 3.1)• 10 Transient Thrombocitopenia, 2 neutropenia• Any BLEEDING

NeoAdjuvantChemotherapy (NAC)

Galosi AB et al. European Urology 2013;64 (3): 519-21

Galosi AB et al. European Urology 2013;64 (3): 519-21

Galosi AB et al. European Urology 2013;64 (3): 519-21

Staging before and after NAC

Stage Before NAC pT0-pT1 pT2 pT3 pT4/R1 N+

≤ T2a 3/10 3 - - - -

cT2b-T3 18/10 1 8 8 - 1

cT4 – N1 9/10 - - 1 8 9

After NAC Radiological re-Staging

• Complete remission 2/30 (6,7%)

• Reduction ≥50% 16/30 (53,3%)

• Stable or Reduction < 50% 9/30 (30%)

• Progression (cT3 to cT4 N+) 3/30 (10%)

Pathological Stage

Pathological outcome

CYST (n=44) NAC+CYST (n=30)

pT0 0 0

pT1-CIS 9 4

pT2 17 9

pT3 13 9

pT4 / R1 5/0 8/7

N+ 7 (16%) 10 (30%)

CLINICAL STAGING VS PATHOLOGICAL

BLADDER CANCER FAILURE TO LOCAL

TREATMENT

cT1+/-CIS

MUSCLE INVASIVE EARLY STAGE

cT2

MUSCLE INVASIVE LATE STAGE c T3-T4a +/- Hydronephrosis

pT0 – pT1 CIS pT2 -pT3 pN+pR+

pT4b

Surgical outcomes

CYSTECTOMY NAC+CYST• Urinary Diversion

– Ureter-Cutaneous 8 6– Ileal-Conduit 30 21– Neobladder 5 2

• + Urethrectomy 7 2• Lymph-node dissection 44/44 30/30• N° LN removed 21 (10-33) 20 (9-44)• Peridural analgesic 21 9• Ileus 4 1• Start oral liquid (POday) 4 (2-5) 3 (2-4)

Surgical oucomesCYST (44) NAC+ CYST (30)

PRE-OP HB 13.2 (10.1-15) 11.3 (8.4-16)

PRE-OP PLT 223 (158-286) 174 (76-474)

TRASFUSION PRE-OP 1 1

TRASFUSIONE INTRA-OP 27 (61%) mean 1.3 U (1-2) 21 (70%) mean 2 U (1-3)

TRASFUSION POST-OP 27 (61%) mean 2 U (1-3) 24 (80%) mean 1.2 U (1-3)

Overall >3 BLOOD UNITS 7 (16%) 9 (30%)

RE-OPERATION/ENDOUROLOGY 0/0 0/0

CARDIAC 4 2

POLMUNARY 2 0

INFECTION 6 4

BOWEL /ANASTOMOSIS 1/0 0/0

DVT/TE 2 3

Re-admission <30 days 1 1

Surgical oucomesCYST NAC + CYST

HOSPITAL STAY 13.6 (8-24) 12 (8-16)

BMI 26.9 25.7

BMI >30 2 0

Wound deiscence/infection 3 1

Pre-op treated AbodminalAortic/Iliac Aneurism

1 1

URETERIC STRICTURE 0 0

Survivalmean FU 22 months [4-42]

CYST NAC+CYST

• FU mean 22 mo 22 mo

• 90-day mortality 2/44 1/30

• Other cause death 5/44 (11,3%) 2/30 (0,6%)

• Cancer related Death 12/44 (27,3%) 7/30 (23,3%)

• Overall Survival 25/44 (56%) 20/30 (66,6%)

• Alive with recurrence 7/44 (15,9%) 5/30 (16,6%)

• Alive without cancer 18/44 (40,1%) 15/30 (50%)

Timing of Cystectomy After NAC

• From initiation of NAC (first day) to surgery

– 16.6 w (range, 6 -195 w; 25°-75°: 13.9 - 21.6 weeks)

• From termination of NAC (last day) to surgery

– Our experience: 4.8 w (range 3-9.5w)

– 6.9 w (range, 2-179 w; 25°-75°: 5.3 - 9.1 weeks)

• From TUR to surgery included NAC

– Our experience: 19 w (range 12-22.4)

Cancer 2012;118:44-53.

• NAC time added

–12 w (10-16w)

• Improved scheduling in Operating Room

Timing of Cystectomy After NAC

CYSTECTOMY FOR BLADDER CANCER

NEO-ADJUVANT CHT

MUSCLE INVASIVE LATE STAGE T3-T4a +/-

Hydronephrosis

MUSCLE INVASIVE EARLY STAGE - T2

BLADDER CANCER FAILURE

TO LOCAL TREATMENT

UROLOGIST POINT OF VIEW• Neoadjuvant chemo is feasible in daily practice

(up to 40%)• Downstaging (30%), Downsazing (80%)

• It doses not increase major complications– We observed an increased rate of asymptomatic

TVP/TE after NAC termination

• Close collaboration with multidisicplinary team– Identify the right patient– High Risk MIBC (MDACC criteria)

• mass after thorough TUR• cT4a• Lymphovascular invasion• Hydronephrosis;• Micropapillary, small cell