Giovanni Scambia Polo Scienze della Salute della Donna e del Bambino
Il parere dell’esperto
• Ovarian cancer in the Era of Personalized Medicine
• Tailored Surgery for Ovarian Cancer
• Cervical cancer
Menagin Ovarian Cancer in the Era of Personalized Oncology
OC is not one disease Outcome depends on histotype
PARP inhibitors in ovarian cancer: current status and future promise
OLAPARIB (Lynparza ®) FDA approved: mantainance therapy in platinum sensitive relapse high grade ovarian cancer + Deleterious BRCA mutation associated with advanced ovarian cancer EMA approved: mantainance therapy in BRCA + platinum sensitive relapse high grade ovarian cancer
NIRAPARIB (Zejula®) FDA + EMA approved: mantainance therapy in platinum sensitive relapse high grade ovarian cancer
RUCAPARIB (Rubraca®) FDA approved: Deleterious BRCA mutation associated with advanced ovarian cancer
VELIPARIB
TALAZOPARIB
Quality of Life?
NACT RATIONALE in ONCOLOGY
NACT in ADVANCED OVARIAN CANCER Clinical evidences supporting NACT Potential risks of NACT Catholic University management
NACT PERSPECTIVES “Tailored” treatment
ITEMS
Neoadjuvant ChemoTherapy: PRINCIPLES
New strategy to increase resectability (“to downstage” the patient) on head and neck cancer
1982
To shrink the tumor in patients who were not candidates for primary surgery, and to allow
organ preservation reduction of mortality rate
1990s-2010s
PROSTATE CANCER
BREAST CANCER
COLO-RECTAL CANCER
LUNG CANCER
Cancer statistics, 2017
A.Fagotti et al. (EJC - 2016)
RESIDUAL DISEASE
EARLY (<30days) COMPLICATIONS LATE 1-6 months from surgery) COMPLICATIONS
NACT vs PDS: RCTs Single institution Phase III Randomised clinical trial
110 eligible women, 55 assigned to arm A (PDS) and
55 to arm B (NACT+IDS)
AEOC supposed resectable women with PI > 8 or < 12 (considered as HTL) were included
2 arms: A) PDS followed by systemic adjuvant chemotherapy ; B) NACT followed by IDS
2 Co-primary outcomes: post-operative complications & PFS
- NACT /IDS is better than PDS in patients with HTL (PI >8 and < 12) in abdomen, as assessed by s-LPS, in terms of perioperative morbidity
- No differences in QoL measurements at the end of treatment between the 2 arms.
PATIENTS’ SELECTION
SURGICAL EFFORT
High and uniform SCS Procedures endowed with high SCS (score =2-3) were
required in 100% versus 48.1%, in PDSarm versus NACT/IDS arm , respectively (p = 0.0001)
Gynecologic Oncology - 2015
Level of evidence: IIB
MIS approaches may be useful when evaluating whether maximum cytoreduction can be achieved in newly diagnosed and recurrent OC109,122,123,135,136
Variation in NACT at high volume hospitals
Gynecologic Oncology - 2017
11.574 pts with FIGO stage IIIC – IV of OC.
78.4% received PDS, while 21.6% treated with NACT/IDS.
All woman treated at 55 high volume hospitals (>20 cases/year), classified in: • Low utilization of NACT (14) • Average utilization of NACT
(31) • High utilization of NACT (10)
Utilization of NACT to treat stage IIIC and IV OC varies widely among high volume hospitals. Receipt of care at a hospital with an average or high NACT use rate was associated with a decreased rate of death compared to care at a low utilization hospitals.
It is plausible that low utilization of NACT is associated with increased suboptimal primary cytoreductive surgery rates and increased major postoperative complications with adjuvant treatment delays, both leading to decresed survival. Further research is needed.
NACT+IDS pts showed more frequently carcinomatosis, and platinum-resistant disease at recurrence compared with PDS
Patients treated with NACT+IDS showed a shorter Post-Relapse survival compared with PDS (3-yrs PRS, PDS=58% vs NACT-IDS=18% )
NACT-IDS negatively influences the pattern and timing of recurrence, probably favoring the selection
of chemoresistant clones
Potential risks of NACT Annals of Surgical Oncology, 2013
Potential risks of NACT 2015
Incorporation of Bevacizumab into upfront regimens
prolongs PFI in AOC patients, but is associated with a
more aggressive behaviour of recurrent disease:
1) Wider presentation of relapse ( p 0.035)
2) Lower percentage of patients suitable for SCS ( p
0.016)
3) Shorter TTP to second line chemotherapy in women
with platinum-sensitive disease (p-value ( p-value 0.041)
2016
Gynecologic Oncology
CATHOLIC UNIVERSITY MANAGEMENT OF AOC
· OVARIAN CANCER SURGERY - GUIDELINES ·
1
OVARI AN CANCER SURGERY
GUI DEL I NES
- Complete report -
·OVARIANCANCERSURGERY-GUIDELINES·
1
OVARIANCANCERSURGERY
GUIDELINES
-ASSESSMENTFORM-
SURNAME:
FIRSTNAME(S):
COUNTRY:
PLEASEPROVIDEYOURDISCIPLINE(S)ORSPECIALITY(IES):
·OVARIANCANCERSURGERY-GUIDELINES·
3
ALGORITHMFOREPITHELIALOVARIANCANCERSURGERY(2)
Stronglydisagree Indecision Stronglyagree
ò ò ò 1 2 3 4 5 6 7 8 9
Doyoufeelthatthisalgorithmisclinicallyrelevant?
Doyoufeelthatthisalgorithmisusableinyourpractice? ·
Opencommentary-Elementssupportingyourposition(e.g.clinicalarguments,bibliographicdata,etc.) ·
MANDATORYifatleastonescoreis<7(optionalinothersituations)
S-LPS
Vizzielli score
S-LPS
Vizzielli score
31
MINIMALLY INVASIVE SURGERY after NACT
Am J Obstet Gynecol 2016
Minimally Invasive-IDS in patients with clinically complete response to NACT seems to be feasible
and safe in terms of perioperative outcomes,
psycho-oncological impact, and survival rate.
A high level of satisfaction was informally recorded for our patients, in line with the fact that a scarless surgery may help to avoid an unnecessary mark of a difficult history,
and reduce postoperative pain.
Multicentric phase II Clinical Trial Of 184 advanced EOC patients
considered eligible for IDS, finally 30 woman received the planned treatment of MI-IDS.
Minimally invasive approach could represent an advantageous alternative surgical way to perform interval debulking surgery in this specific subset of patients.
MIS is superior to standard laparotomy in terms of EBL, discharge time and TTC.
MI approach determines a higher percentage of women with positive well-being compared to pts treated
with the conventional approach.
Women treated with
MI-IDS showed a 6
months longer PFS compared
to Controls
MINIMALLY INVASIVE SURGERY after NACT
Gyn Oncology - 2016
• Retrospective cohort study • 3.071 pts with AOC, who
underwent NACT and IDS • 47.5% LPS vs 52.5% LPT
No difference in survival between women who underwent laparoscopic IDS and those underwent laparotomy.
Short postoperative hospitalization after laparoscopic surgery and no difference in risk of unplanned readmission or perioperative death.
In well-selected pts, such as those who have a complete response to NACT, laparoscopic IDS may be a safe and effective alternative to laparotomy.
• Relatively short FU (3 ys) • Lack of random allocation • Inability to verify registry
data
• Retrospective case-control study
• 30 AEOC pts treated with MI-IDS; 65 submitted to LPT-IDS
• Small sample size
• Short duration of median FU
AOC pts with BRCAmut are highly responsive to P-based
chemotherapy, with also prolonged PFS after NACT, compared
with BRCA naïve. Gorodnova TV, et al. Cancer Letter, 2015;
Mahdi H, et al. Gynecol Oncol 2015
MOLECULAR CHARACTERIZATION FOR NACT
PDS
NACT
Submitted
Pro
gre
ssio
n-f
ree
surv
ival
(%)
PDS
NACT
p=0.05
p=ns
BRCAwt
PDS
NACT
Median PFS
26 months
18 months
BRCAmut
PDS
NACT
Median PFS
28 months
24 months
Neoadjuvant ChemoTherapy: PRINCIPLES
New strategy to increase resectability (“to downstage” the patient) on head and neck cancer
1982
To shrink the tumor in patients who were not candidates for primary surgery, and to allow
organ preservation reduction of mortality rate
1990s-2010s
PROSTATE CANCER
BREAST CANCER
COLO-RECTAL CANCER
LUNG CANCER
Cancer statistics, 2017
To test the activity of a therapeutic
approach or the potential importance of biological factors in
determining disease outcome
2017
Achiving a complete pathologic response seems to correlate to
the best prognosis ever achieved
2010s
J Clin Oncol 30:1796-1804, 2012
Ann Surg Oncol (2012 ) BREAST CANCER
COLO-RECTAL CANCER
LUNG CANCER
AJOG (2014)
OS PFS
PATHOLOGICAL RESPONSE TO NACT
• cPR: cases with no residual neoplastic cells in all the surgical specimens,
including the adnexa
• microPR: microscopic foci (maximum diameter ≤ 3 mm)
• macroPR: persistent macroscopic site of disease after NACT
• cPR is an uncommon event in AOC patients receiving NACT and is associated with a longer PFS and OS compared with women showing no cPR
• cPR, rather than only an estimation of disease extension after NACT, clearly emerges as a marker of extreme sensitivity to platinum-based chemotherapy.
Neoadjuvant ChemoTherapy: PERSPECTIVES
Neoadjuvant ChemoTherapy: PERSPECTIVES
BRCA1=27%
Olaparib with weekly JM8 and TAX as NACT in BRCA mut advanced HGSOC women: a PHASE II multicentric study
PRIMARY AIM: Pathological complete response after 3 cycles of NACT including OLAPARIB and weekly JM8-TAX in BRCAmut advanced HGSOC SECONDARY AIMS: Complete cytoreduction rate at IDS, response rate (RECIST criteria), surgical assessment of response with a laparoscopic standardized score (Fagotti score), toxicity Profile, PFS,OS.
Suspicious AEOC : GYO + imaging + S-LPS
TISSUE ACQUISITION Histology & molecular analysis
TUMOUR LOAD & peri-op risk
LTL/ITL<8 Low peri-op risk PDS
HTL 8-12 High peri-op risk
CHEMORESISTANT (LGSOC; mucinous; BRCA wt)
CHEMOSENSITIVE (High grade; BRCA mut; TGF-beta pathway)
Discuss with the pt PDS or NACT Offer exp. treatment
NACT with target treatment
Unresectable NACT
75%
<5%
20-25%
Catholic University Integrated Algorithm for Personalized Treatment in HGSOC
CONCLUSIONS...
We are moving from generalized guidelines, where PDS is still against NACT, to tailored approaches where PDS and NACT are both
first-line available treatments that we need to carefully choose for EACH patient
DON’T MAKE IT LOOK GOOD ON YOU BUT
MAKE IT GOOD FOR YOU
KEY POINTS
•
• CARATTERIZZAZIONE MOLECOLARE
• CHIRURGIA TRATTAMENTO MEDICO •
where are we going ?
Unanswered questions Early stage and fertility sparing tratments Sentinel node Adjuvant treatment
Local Adavenced disease (Prognostic groups)
Neoadjuvant chemotherapy
Metastatic cervical cancer
Target Therapy
What is the appropriate endpoint? Should we do phase II or phase III studies? Proposed primary endpoints included overall survival (OS), progression free survival (PFS), and response rates (ORR). Secondary endpoints included PFS, quality of life (QOL), patient reported outcomes (PRO), and safety
News in cervical cancer ?
Int J Gynecol Cancer. 2016 Jan;26(1):199-207
Feb-1999: NCI issues clinical announcement on cervical cancer
1.reduction in risk of death (HR 0.69, 95% CI 0.61-0.77)
2.reduction in risk of local recurrence (OR 0.59, 95% CI 0.50-0.69)
3.trend in reduction of distant metastasis (OR 0.81, 95% CI 0.65-1.01)
I.V. CISPLATIN CHEMOTHERAPY
Cisplatin 40mg/m2 (Max dose 70mg)
IV q wk during RT (6wks)
EXTERNAL BEAM
pelvic
radiation(40 to 60 Gy)
BRACHYTHERAPY
(8,000 to 8,500 cGy
to Point A)
CTRT: CONSIDERED THE WORLD STANDARD TREATMENT for LACC
OTHER OPTIONS
• Chemo/radiation
• Chemo/radiation followed by surgery
• Neoadjuvant chemotherapy
• followed by surgery
• followed by chemo/radiation
• Trial closed for poor accrual
• No difference OS between
surgery vs no surgery after
CTRT
• This study failed to
demonstrate that RH after
EBRT-CT is superior to
standard BCT
Accrual: 103 pts
Eligibility
Cervix carcinoma stage
IB2-IVA
Age<80y
Adequate bone marrow
function
Adequate renal function
Normal liver function
T
Clinical Response -CR 36 pt(34.9%)
-PR 63 pt(61.2%)
-SD 2 pt(1.9%)
-PD 2 pt(1.9%)
RT 39.6 GY(PELVIC LYMPH NODE DRAINAGE, BULKY
TUMOR,PARAMETRIA) + 10.8 GY(PRIMARY
TUMOR,PARAMETRIA)
CT CISPLATIN 20 MG/M2 P1Q25+CAPECITABINE 1300
MG/M2 DAILY
DFS 73%
OS 86.1%
TOXICITY
-Leukopenia 19.4% G1
19.4% G2
-Gastrointestinal 32% G1
9.7% G2
-Genitourinary 11.6% G1
2.9% G2
RELAPSE 25 pt(24.3%)
DEATH 10 pt(9.7%)
Ferrandina et al. Int J Radiat Oncol Biol Phys 2014
RADICAL
HYSYTER
ECTOMY
3 years
OTHER OPTIONS
• Chemo/radiation
• Chemo/radiation followed by surgery
• Neoadjuvant chemotherapy
• followed by surgery
• followed by chemo/radiation
NACT: AIMS
DEBULKING EFFECT AND TUMOR SIZE REDUCTION
IMPROVING SURGICAL OUTCOMES
BETTER ACTIVITY AGAINST MICROMETASTASIS
PERMIT CONSERVATIVE SURGERY
LESS TOXICITY
EASIER MANAGEMENT OF SALVAGE THERAPY
OTHER OPTIONS
• Chemo/radiation
• Chemo/radiation followed by surgery
• Chemo/radiation-chemotherapy
• Neoadjuvant chemotherapy
• followed by surgery
• followed by chemo/radiation
IB2 to III stages
Tierney et al. Eur J Cancer 2003
• 5 randomized trials
• 872 pts (97% of total)
• Stage:
IB 35%
II 38%
III 26%
NACT & RS vs RT
EORTC 55994 (started 1999 !!!)
INCLUSION CRITERIA
•FIGO IB2, IIA, IIB
•PS 0-2
•Age 18-75
•Squamous
•Adenocarcinoma
•Adenosquamous
STRATIFICATION
• FIGO
• Institution
• Age 18-50 vs 50-75
• Histology:
Squamous vs
Adenocarcinoma vs
Adenosquamous
ENDPOINTS
• Primary: OS
• Secondary:
PFS
Toxicity
QoL
R
A
N
D
O
M
Cisplatin based chemotherapy:
Min. total dose of 225 mg/mq
25 mg/mq per week
Final dose no later than 8°week
Radical hysterectomy
Chemo-radiotherapy
• CDDP 40 mg/mq (6 week) + EBRT 45-50 Gy
OTHER OPTIONS
• Chemo/radiation
• Chemo/radiation followed by surgery
• Chemo/radiation-chemotherapy
• Neoadjuvant chemotherapy
• followed by surgery
• followed by chemo/radiation
TREATMENTS IN LACC
• Chemo/radiation
• Chemo/radiation followed by surgery
• Neoadjuvant chemotherapy followed by chemo/radiation
• Neoadjuvant chemotherapy followed by surgery
CHEMOTHERAPY IS MANDATORY!
But how can we choose???
KEY QUESTIONS
Carboplatin or cisplatin?
WHICH Platinum doublet?
Which role for TARGET THERAPY in CC?
+2,2 m
+3,5 m
CECILIA (MO29594): trial design
• AUC, area under the concentration curve; q3w, every 3 weeks *Minimum of 6 cycles, unless toxicity necessitates discontinuation of one or both chemotherapy agents, in which case non-implicated drug(s) and Bevacizumab can be continued alone
Metastatic, recurrent or persistent cervical
cancer patients not amenable to curative treatment with surgery
and/or radiation therapy
n=150
Until disease progression, unacceptable
toxicity or withdrawal of consent
Paclitaxel 175mg/m2 q3w*
Carboplatin AUC5 q3w*
Bevacizumab 15mg/kg q3w
A MULTICENTRE OPEN-LABEL SINGLE-ARM PHASE II STUDY
EVALUATING THE SAFETY AND EFFICACY OF Bevacizumab IN
COMBINATION WITH CARBOPLATIN AND PACLITAXEL IN PATIENTS
WITH METASTATIC, RECURRENT OR PERSISTENT CERVICAL CANCER
MO29594– Adapted from
https://clinicaltrials.gov/ct2/show/NCT02467907?term=bevacizumab+cervical&rank=5
Randomize
Carboplatin AUC5 +
Paclitaxel 175mg/m2+
Nintenanib 200 mg Bid
Weeks 1-6
Nintenanib
until progression
Primary End-point: PFS
Secondary End-point: OS, Toxicity, Patient Health status
Ongoing Trial: Phase II, randomized, double bind and placebo
controlled trial
Carboplatin AUC5 +
Paclitaxel 175mg/m2+
Placebo Bid
Weeks 1-6
Placebo
until progression
Figo IVB/recurent disease
NINTENANIB
Advanced cervical
carcinoma (FIGO
stage IIB-IIIB or IB-
IIA with pelvic node
metastasis and/or
tumour size ≥ 5 cm
n=57
RT/BRT 45 Gy (over 5 ws in 25 once daily fractions)
Bevacizumab 10 mg/kg Iv q2 weeks (days 1, 15 and
29, total 3 doses) during chemoradiation, before
cisplatin and on the same day as cisplatin
Phase II, single arm trial
Primary endpoints: treatment-related serious adverse events rates
and adverse events rates within the first 90 days
Secondary endpoints: treatment-related serious adverse events rates
and adverse events rates at any time, DFS, OS, angiogenic markers
Schefter et al IJR Oncol Biol Phys. 2012,2014
The Catholic University GYO Network
Dpt. Ob/GYN Gemelli Hospital, Rome
Dpt. Oncology Centre for Research, Campobasso
Campobasso
Chieti
Acquaviva delle Fonti
Palermo
Novara Abano Terme
Gyn Onc Unit University of Palermo
Gyn Onc Unit University of Chieti
Gyn Onc Unit University of Piemonte Orientale
Gyn Onc Unit Miulli Hospital,
Acquaviva delle Fonti
SITE Essen criteria Leuven criteria
Abdominal metastases
Multiple parenchymatous liver metastases Infiltration of large parts of the pancreas (not only tail) and/or the duodenum Infiltration of the porta hepatis or truncus coeliacus Deep infiltration of the radix mesenterii Diffuse and confluent carcinomatosis of the stomach and/or small bowel Involvement of the SMA
Intraephatic metastases Infiltration of the duodenum and/or pancreas and/or the large vessels of the porta hepatis or truncus coeliacus
Extra-abdominal metastases
Not completely resectable metastases All, excluding: resectable inguinal lymph nodes, solitary retrocrual or paracardial nodes, Pleural fluid cytologically malignant cells without presence of pleural tumors
Pts characteristics Poor PS-ECOG
Vergote I and Du Bois A, 2012
Criteria for suboptimal debulking surgery in AOC
Borley J, BJOG, 2014
Predictive performances of CT scan in AEOC
findings confirm previously reported results (Bristow et al, 2000;Chi et al, 2000; Cooper et al, 2002; Saygili et al, 2002; Memarzadehet al, 2003), and definitively recognise the extent of the impactplayed by ECOG-PS in the preoperative prediction of ovariancancer primary resectability (Aletti et al, 2007). The models basedon diagnostic performance and on results from multivariate
analysis showed the same accuracy in predicting the chance ofoptimal cytoreduction, although they included slightly differentCT-based features; in particular, involvement of bowel mesentery,omentum, liver, and diaphragm were shown to fulfil all therequired criteria (Bristow et al, 2000) in Approach A, whereas inmultivariate analysis the involvement of peritoneum and suprar-enal aortic lymph nodes, besides bowel/mesentery and diaphragmdisease, were independently associated with suboptimal cyto-reduction. The divergence between the two approaches remainsdifficult to explain, although the strict and, to a certain extent,unpredictable associations among the variables might more likelyhave an impact on multivariate analysis. In any case, our findingssupport the relevance of the assessment of the status of bowelmesentery and diaphragm involvement, recognised among themost important features determining the feasibility of ovarian
Table 4 Prediction of optimal cytoreduction: univariate and multivariate analysis by logistic regression of CT-based and clinically assessed parameters to
use for modeling (Approach B)
Univar iate Mult ivar iate
v2 P-value v2 P-value Point a
RadiographicPeritoneal thickening, peritoneal implants 4 2cm 16.34 0.0001 3.45 0.063 1
Bowel mesentery involvement 17.50 0.0001 5.35 0.0207 1Omental extension (spleen, stomach, lesser sac) 11.13 0.0008 2.52 0.11 0
Pelvic sidewall involvement and/or hydroureter 2.28 0.13 — — 0
Suprarenal aortic lymph nodes 4 1cm 4.21 0.040 4.36 0.036 1Infrarenal aortic lymph nodes 4 2cm 8.15 0.0043 — — 0
Superficial liver metastases 4 2cm and/or intraparenchimal liver metastases any size 8.58 0.0034 — — 0Large volume ascites (4 500ml) 8.15 0.0043 — — 0
Diaphragmatic disease (widespread infiltrating carcinomasis, or confluent nodules) 25.35 0.0001 7.13 0.0076 1
Clinical
Age, years (p 65 vs 4 65) 2.51 0.08 — — 0Ca125 levels (p 500 vs 4 500 IU ml 1) 2.98 0.11 — — 0
ECOG-PS (0,1 vs 2) 19.71 0.0001 14.22 0.0002 1
aOnly variable achieving a P–value o 0.10 were assigned a point value. Statistically significant values have been indicated as bold values.
0
10
20
30
40
50
60
0 1 2 3 4
Co
unts
PI
5
Model 3
Model 4
0
0.2
0.4
0.6
0.8
1.0
0 0.2 0.4 0.6 0.8 1.0
Sensitiv
ity
1-Specificity
Model 3
Model 4
Figure 2 Distribution of predictive index values (A) and ROC curves(B) in Model 3 and Model 4.
Table 5 Pre-test probability, likelihood ratio, and post-test probability for
different predictive models of primary optimal cytoreduction in ovarian
cancer
Test Cutoff
Pre-test
probabilit y
Posit ive
likelihood rat io
Post -test
probabilit y
Model 2 5 55.8 9.86 92.6Model 4 3 55.8 10.25 92.8
Table 6 Performance of Approach A (Model 2) in defining the rate of
patients unnecessarily explored or inappropriately unexplored
Model 2
PIVUnnecessar i ly explored
(1 NPV) (%)Inappropr iately unexplored
(1 PPV) (%)
0 17.9 28.81 25.0 27.6
2 33.3 19.43 39.0 18.2
4 48.1 16.35 50.0 7.4
6 53.6 5.0
7 54.3 0
CT scan and cytoreduct ion in ovar ian cancer
G Ferrandina et al
1070
British Journal of Cancer (2009) 101(7), 1066–1073 & 2009 Cancer Research UK
Clin
ical
Stu
die
s
Ferrandina G, BJC, 2009
1-Specificity
Sen
sitiv
ity
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
AUC= 0.758
Suidan RS, Gyn Onc, 2014
AUC3= 0.78
AUC4= 0.82
Rutten IJGC, IJGC, 2016
Ferrandina (model B) AUC
0.82
Reader 1 0.55
Reader 2 0.60
Reader 3 0.59
NACT RATIONALE in ONCOLOGY
NACT in ADVANCED OVARIAN CANCER Clinical evidences supporting NACT Potential risks of NACT Catholic University management
NACT PERSPECTIVES “Tailored” treatment
ITEMS
CHORUS TRIAL Kehoe et al, Lancet 2015
NACT vs PDS: RCTs • Selection bias in
recruitment of patiens believed to be inoperable with high tumor load
(Fotopolou at al. JCO-2017)
PFS = 12m (IDS) vs 10,7 m (PDS)
mOS= 24,6m (IDS) vs 22,6 m (PDS)
EORTC TRIAL Vergote et al, NEJM, 2010
mOS = 30 m (IDS) vs 29 m (PDS)
Low survival rates due to: • 1) patients’
selection; • 2) surgery was
substandard compared with that in other trials;
(S.Chi at al. “is the easy way ever the better way?”JCO-2011)
• Multicentric RCT (87
hospitals in the UK and New Zealand)
• 550 women with FIGO stage III or IV of OC randomized
• 276 PDS vs 274 NACT/IDS
• Median FU: 52m
• Multicentric RCT (59
institutions)
• 718 pts enrolled, 670 women with biopsy-proven FIGO stage IIIC or IV OC randomized
• 336 PDS vs 334 NACT/IDS
• Median FU: 55m
Although these trials show non inferior results of NACT with lower morbidity,
they have not neglegible bias in terms of PATIENTS’ SELECTION and SURGICAL
EFFORT
NACT RATIONALE in ONCOLOGY
NACT in ADVANCED OVARIAN CANCER Clinical evidences supporting NACT Potential risks of NACT Catholic University management
NACT PERSPECTIVES “Tailored” treatment
ITEMS