UNIVERSITY OF PERUGIA

Department of General and Emergency Surgery

Chief: Prof. Annibale Donini

COLON CANCER

PERITONEAL CARCINOMATOSIS

TREATMENT

Prof. Annibale Donini

COLON CANCER IS A HIGHLY FREQUENT NEOPLASIA

From IARC Cancer Base 2013

From IARC Cancer Base 2013

MORTALITY REMAINS RATHER HIGH ALTHOUGH SCREENING AND MODERN CHEMOTHERAPY DRUGS

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CC PERITONEAL CARCINOMATOSIS EPIDEMIOLOGY

Retrospective analysis of a prospective database with a literature review

COLON CANCER POPULATION

STAGE IV AT DIAGNOSIS: 20%

LIVER METASTASES 74,5%

PERITONEAL CARCINOMATOSIS 24%

ONLY PC 45%

PC AND OTHER 55%

CC PERITONEAL CARCINOMATOSIS EPIDEMIOLOGY

CC PERITONEAL CARCINOMATOSIS 3-28%

SYNCRONOUS CC PC 7-10%

METACHRONOUS CC PC 4-44%

*High Variability for the difficult diagnosis of PC

Prognostic Factors of PC Occurence

Prognostic Factors of PC Occurence

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Peritoneal Carcinomatosis ? Metastasis

Are the benefits of sistemic chemotherapy alone so great that Cytoreductive Surgery and perioperative chemotherapy is not needed ?

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5Y-OS AND DFS IN PTS WITH CC PC TREATED WITH CRS AND CH-TR

Median Survival: 12,6 months Median DFS: 7 months

Overall Survival in patients with PC compared to other metastatic sides

5-FU; Leucovorin; Oxaliplatin

5-FU; Leucovorin; Irinotecan

Oxaliplatin; Irinotecan

Conclusion: - Shorter OS and DFS when PC

- 5-y survival with Folfox (all pts: 4%)

PC is a LOCAL REGIONAL PROGRESSION that represent the natural hystory

of all GI Cancer

IP CHEMOTHERAPY

IV CHEMOTHERAPY

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Median Survival: 22,4 (HIPEC) vs 12,6 (control) monnths

Journal of Clinical Oncology 2004

Median Survival: 62,7 (HIPEC) vs 23 (CONTROL) months

Retrospective Analysis: 2009

Median Survival: 34,7 (HIPEC) vs 16,8 (CONTROL)months

Retrospective Analysis: 2010

5y-OS: 35% 5y-DFS: 16%

PRODIGE 7: FRENCH RANDOMIZED TRIAL Waiting for final results Accruiment of 264pts

PERITONEAL CARCINOMATOSIS

CITOREDUCTIVE SURGERY; PCI<24

HIPEC WITH OXALIPLATIN

ADJUVANT CHEMOTHERAPY 6 FOLFOX CYCLES

NO HIPEC

RANDOMIZATION

Kindly provided by Prof Glehen

VERY DIFFICULT PTS ACCRUIMENT!

Median Survival: 25 (HIPEC) vs 18 (CONTROL) months P<0.04

5y-PFS: 17%(HIPEC) vs 0% (CONTROL) months P<0.04

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Completeness of Cytoreduction Score

Peritoneal Cancer Index

CC SCORE IS A STRONG INDICATOR OF SURVIVAL (P<0.001)

PCI IS A STRONG INDICATOR OF SURVIVAL (P<0.001)

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How much does it cost ?

Analysis of 26 series of patients affected by CC PC treated with CRS and HIPEC

POST-SURGICAL OUTCOMES: •MORBIDITY II-IV according to Clavien Dindo: 12-48% •PROCEDURE RELATED MORTALITY: 1-5,8%

COMPARABLE TO THAT OF MAJOR GI SURGICAL PROCEDURES (WHIPPLE PROCEDURE)

MORBIDITY: GRADE III-IV • CHEMOTHERAPY ARM: 50% • SURGERY ARM: 42% GRADE V • O% IN BOTH ARMS

GRADE RACCOMMANDATION B

UNSOLVED PROBLEM:ME

TACHRONOUS PC

“PATIENT IS KILLED BY WHAT THE SURGEON DOESN’T SEE”

P. H. SURGARBAKER

Clinical and intraoperative histophatologic features of the primary cancer as an estimate of the incidence of

Subsequent metacronous peritoneal metastases

CLINICAL FEATURES INCIDENCE OF PERITONEAL

METASTASES DURING

FOLLOW-UP (%)

1. PERITONEAL NODULES 70

2. OVARIAN METASTASES 60

3. PERFORATION 50

4. INVASION OF ADJACENT ORGAN OR

STRUCTURES 20

5. SIGNET REING HISTOLOGY 20

6. FISTULA 20

7. OBSTRUCTION 20

HYSTOPATHOLOGIC FEATURE

8. POSITIVE MARGIN RESECTION 80

9. POSITIVE PERITONEAL LAVAGE 40

10. LYMPHNODES POSITIVE AT MARGIN

OF RESECTION 20

11. T3/T4 MUCINOUS CANCER 40

Prophylactic HIPEC or second look

Kindly provided by Prof Sugarbaker

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PC and Second-look

Rational : For minimal PCI HIPEC could be the most efficient approach. But early detection of minimal PC is not possible neither with clinical signs neither with imaging studies. THUS It is logical to propose a second-look to asymptomatic patients presenting high risks to develop a PC, with the aim to treat PC at an early stage.

ETHICAL PERSPECTIVE IN PATIENTS AT HIGH RISK OF PC

- THE COST OF PROPHYLACTIC HIPEC –MINIMAL COST, ACCEPTABLE MORBIDITY - COST OF NOT USING PROPHYLACTIC HIPEC-DEATH FROM PERITONEAL METASTASIS -IN THE FUTURE THERE MUST BE A MULTI-ISTITUTIONAL CLINICAL TRIAL. I WILL ENCOURAGE MY PATIENTS TO ENTER. UNTIL MORE DATA BECOMES AVAILABLE I WILL ROUTINELY USE PROPHYLACTIC HIPEC IN SELECTED PRIMARY GASTROINTESTINAL CANCER PATIENTS

Kindly provided by Prof Sugarbaker

5Y-OS (%): 85 (EXP) VS 55 (CONTROL)

5Y-DFS (%): 90 (EXP) VS 60 (CONTROL)

OVERALL SURVIVAL

5YOS (%): 90 (EXP) VS 40 (CONTROL)

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2007 2015

65 treated patients

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OUR EXPERIENCE FROM 2007 TO DATE: Primary Tumor Distribution

Colon Cancer OUR EXPERIENCE from 2008 650 colon cancer surgically treated 28 (5%) pts with peritoneal carcinomatosis 74% synchronous PC 26% metachronous PC

Patients Features

Mean Age 59yo

Mean PCI 4,5

Side

Right Colon 43,5%

Left Colon 52,5%

Rectum 4%

Mmytomicin plus Cisplatin

43,5%

Oxaliplatin 56,5%

23 CRS + HIPEC 5 CRS

OUR EXPERIENCE from 2008

RESULTS (1)

5y-OS: 45%; MEDIAN SURVIVAL 60 MONTHS vs 28 months (only CRS)

OUR EXPERIENCE from 2008

RESULTS (2)

MORBIDITY: GRADE III-IV • 4.3% GRADE V • 4,3%

OUR EXPERIENCE from 2008

RESULTS (3)

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Conclusion

SURGEONS

ONCOLOGIST

AN AGREEMENT BETWEEN ONCOLOGISTS AND SURGEONS IS NEAR

Int J Clon Onc 2015