preservación de órgano en cáncer de vejiga

Preservación de órgano en cáncer de vejigaMauricio Lema Medina MD

Clínica de Oncología Astorga, Clínica SOMA, Medellín

Bucaramanga, 05.11.2016

Curso de Urología OncológicaAsociación Colombiana de Urología

Mauricio Lema: Conflicto de interés

Honorarios por conferencias (2016): BMS, Servier, Roche, Novartis, MSD, Aztra-Zeneca, AMGEN, PfizerGrant de investigación:GSK/Novartis

@ONCONERD

Bladder cancer treatment overview

Stage by stage

NCCN Guidelines Version 2.2016: Bladder Cancer


Tis TURBT +/- IVCIf relapsed Tis, orHigh-grade disease

T1 low-grade TURBT+/- IVC or

CystectomyIf residual disease

T1 high-grade Cystectomy

Non muscle-invasive disease

IVC: Intravesical chemotherapy / BCGTURBT: Transurethral resection of bladder tumor


cT2/T3/T4a/N0

NeoAdj CT Cystectomy

Muscle-invasive disease

Cystectomy Adj CTIf pT3/pT4 or N1 or Margin+ disease

Maximal TURBT Chemo-RT CystectomyIf residual disease

Bladder preservation strategy

Chemo-RT

TURBT

RT

Non-cystectomy candidates

Adj: Adjuvant; NeoAdj: NeoadjuvantCT: ChemotherapyRT: Radiation therapyTURBT: Transurethral resection of bladder tumor


cT4b/N+

CT

Unresectable disease

Chemo-RT

Individualize

TURBTRTCTChemo-RTCystectomy

CT: ChemotherapyRT: Radiation therapyTURBT: Transurethral resection of bladder tumor

Cystectomy (& PLND) is a standard option for N0 invasive bladder cancer

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer

Patients with clinical tumor–node–metastases (TNM) stage T2N0M0 to T4aN0M0 bladder cancer who were candidates for radical cystectomy were eligible.

Prior pelvic irradiation was not allowed. Patients were required to have adequate renal, hepatic, and hematologic function and a SWOG performance status of 0 or 1.

Tumors were staged according to the criteria in the fourth edition of the American Joint Committee on Cancer staging manual. Patients had tumors invading the superficial muscle and beyond, to the level of the surrounding viscera (but not to the side wall of the pelvis).

Patients were stratified according to age (younger than 65 years vs. 65 years or older) and stage (T2 vs. T3 or T4a; T2 represents invasion of superficial muscle and T3 invasion of deep muscle or perivesical fat).

They were randomly assigned, with the use of dynamic balancing for stratification, by a central computer at the SWOG Statistical Center to undergo radical cystectomy or to receive three cycles of chemotherapy with M-VAC followed by radical cystectomy.

Barton Grossman, NEJM (2003) 10.1056/NEJMoa022148

T2-T4aN0M0Bladder Cancer

M-VAC + Cystectomy

Cystectomy

R

T hree 28-day cycles of M-VAC, as follows: methotrexate (30 mg per square meter of body-surface area) on days 1, 15, and 22; vinblastine (3 mg per square meter) on days 2, 15, and 22; and doxorubicin (30 mg per square meter) and cisplatin (70 mg per square meter) on day 2.

To compare the survival among patients treated with cystectomy alone with survival among those treated with M-

VAC followed by cystectomy in a randomized phase 3 trial

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer

Barton Grossman, NEJM (2003) 10.1056/NEJMoa022148

Neoadjuvant Chemotherapy in Invasive Bladder Cancer:Update of a Systematic Review and Meta-Analysis of

Individual Patient Data

Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. European Urology (2005)

Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large,

Randomized, Multinational, Multicenter, Phase III Study

Von der Maase, J Clin Oncol (2000)

Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large,

Randomized, Multinational, Multicenter, Phase III Study

Von der Maase, J Clin Oncol (2000)

GC: Gemcitabine 1,000 mg/m2 over 30 to 60 minutes on days 1, 8, and 15 plus cisplatin 70 mg/m2 on day 2.

GC provides a similar survival advantage to MVAC with a better safety profile and tolerability.

Neoadjuvant cisplatin-based CT improves OS in muscle-invasive, cN0,

bladder cancer(GC or M-VAC)

cTNM vs pTNM in bladder cancer

Stage by stage

Clinicopathological outcomes after radical cystectomy for clinical T2 urothelial carcinoma: further evidence to support the

use of neoadjuvant chemotherapy

451 consecutive patients who underwent RC at Fox Chase Cancer Center between January 2000 and June 2009 to identify 212 patients who underwent surgery without prior chemotherapy for cT2 UC.

Patients whose initial transurethral resection was done elsewhere had their slides reviewed by our pathology department.

Clinical staging was based on internal slide review, physical examination and review of the cross-sectional imaging, and was reported according to the 2002 TNM system.

All patients underwent either a CT scan or a MRI of the abdomen and pelvis. Patients underwent RC and bilateral pelvic lymph node dissection, with the proximal extent of dissection to the bifurcation of the common iliac vessels

Canter D, BJUI (2010) 10.1111/j.1464-410X.2010.09442.x

cT2 cN0Bladder Cancer Radical cystectomy + PLND

Study Type – Therapy (case series) Level of Evidence 4

pTNM/Follow-up

MRI / CT stagedTNM 2002

Clinicopathological outcomes after radical cystectomy for clinical T2 urothelial carcinoma: further evidence to support the

use of neoadjuvant chemotherapy

Canter D, BJUI (2010) 10.1111/j.1464-410X.2010.09442.x

Survival after RC for patients with cT2 UC.

Clinical TNM in bladder cancer is highly UNRELIABLE

Radiotherapy (RT) vs Chemoradiotherapy (Chemo-RT) in muscle-invasive bladder cancer

Stage by stage

Cisplatin is nephrotoxic drug and many bladder cancer patients do not have adequate renal function to receive cisplatin safely.

Radiotherapy with or without Chemotherapy in Muscle-Invasive Bladder Cancer (BC2001 Trial)

At least 18 years of age with histologically confirmed stage T2, T3, or T4a bladder cancer (adenocarcinoma or transitional or squamous-cell carcinoma) with no signs of lymph-node involvement or metastasis.

The main inclusion criteria were a performance status of 0 to 2, according to World Health Organization criteria; a white-cell count of more than 4000 per cubic millimeter; a platelet count of more than 100,000 per cubic millimeter; a glomerular filtration rate of more than 25 ml per minute; and levels of serum bilirubin and aminotransferase values of less than 1.5 times the upper limit of the normal range.

On the basis of results of a meta-analysis and the Medical Research Council BA06 trial platinum-based neoadjuvant chemotherapy was permitted but not mandatory.

The main exclusion criteria were pregnancy, a previous cancer or radiotherapy that was likely to interfere with the protocol treatment, or inflammatory bowel disease.

James ND, NEJM (2012) 10.1056/NEJMoa1106106

T2-T4/N0/M0Bladder Cancer

Chemo-RT

RT

R

Fluorouracil: continuous infusion (500 mg/m2/day during fractions 1-5 and 16-20 of RT. Mitomycin C: 12 mg per square meter on day 1.

The primary end point was locoregional disease–free survival

Cystoscopic resection

Cystoscopic resection

Neoadjuvant CT allowed



“There was a trend toward an increased rate of salvage cystectomy in the radiotherapy group (20 patients in the chemoradiotherapy group vs. 31 in the radiotherapy group) for a hazard ratio of 0.58 (95% CI, 0.33 to 1.03; P=0.07)”

Radical cystectomy vs. chemoradiation in T2-4aN0M0 bladder cancer: A case-control study

Gofrit ON, Urologic Oncology (2015) 10.1016/j.urolonc.2014.09.014

Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder

Cancer

Choudhury, J Clin Oncol (2011)

Gemcitabine 100 mg/m2 given as a 30-minute intravenous infusion 2 to 4 hours before RT. Gemcitabine was administered once per week during RT on days 1, 8, 15, and 22

10.1200/JCO.2010.31.5721

50 patients

44 (88%) achieved a complete endoscopic response. 36 patients were alive32 patients had a functional and intact bladder.

14 patients died7 died as a result of metastatic MIBC,5 died as a result of intercurrent disease, 2 died as a result of treatment-associated deaths.

4 patients underwent cystectomy1 patient required a bowel resection for late toxicity.

3-year cancer-specific survival was 82%. 3- year overall survival was 75%.

Chemo-RT improves locoregional DFS in muscle-

invasive, cN0, bladder cancer

Cystectomy vs Chemo-RT in muscle-invasive, N0, bladder cancer

Stage by stage

Radical cystectomy vs. chemoradiation in T2-4aN0M0 bladder cancer: A case-control study

Gofrit ON, Urologic Oncology (2015) 10.1016/j.urolonc.2014.09.014

“Despite having a significantly higher comorbidity index, patients treated with chemoradiation had similar overall and disease-free survival rates with low toxicity. Treatment with chemoradiation should be considered in patients with T2-4aN0M0

bladder cancer.”

Hennigsonh. Radiotherapy and Oncology 62 (2002) 215–225

We identified 71 patients who had had urinary bladder cancer treated with radical radiotherapy before 1995. Forcomparison, 325 patients treated with radical cystectomy and urostomy, continent or non-continent, during the same period and 460individuals randomly selected from the general population were included.

Information was collected by means of an anonymously answered postal questionnaire to avoid investigator-related bias.

Answers were obtained from 58 (82%) radiated patients, 251 (85%) cystectomized patients and 310 (71%) population controls.

Of the radiated patients, 74% reported little or no distress from symptoms from the urinary tract, 38% had had intercourse the previous month and 57% (men) reported they had ejaculated. Among the cystectomized patients, 13% had had intercourse and 0% (men) had ejaculated.

Moderate or much distress from symptoms from the gastrointestinal tract was reported by 32% of the radiated patients, 24% of thecystectomized patients and 9% of the population controls.

After radical radiotherapy, 46% of the patients were willing to accept some risk of decreased survival to become symptom-free.

Conclusions: About 3/4 of these long-term survivors after radical radiotherapy for bladder cancer had a functioning urinary bladder with little or no distress from the urinary tract. The prevalence of sexual dysfunction was lower than after cystectomy and the prevalence of distress from the gastrointestinal tract was comparable

Available, but limited, evidence appears to support Chemo-RT as an

option in potentially resectable bladder cancer

Conclusions• Cystectomy (& PLND) is a standard

option for N0 invasive bladder cancer• Neoadjuvant cisplatin-based CT

improves OS in muscle-invasive, cN0, bladder cancer(GC or M-VAC)

• Chemo-RT improves locoregional DFS in muscle-invasive, cN0, bladder cancer

• Available, but limited, evidence appears to support Chemo-RT as an option in potentially resectable bladder cancer

Foto: Juan José Arango Escobar

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