PICO

Dr. Rafiyandi

To determine the overall survival and relative

effect of multiple prognostic variables in

cohorts of patients with advanced-stage
ovarian cancer treated with platinum-based
neoadjuvant chemotherapy in lieu of primary
cytoreductive surgery.

Twenty-two cohorts of patients with Stage III

and IV ovarian cancer (835 patients) were

identified from articles in MEDLINE (1989
2005)

The mean number of patients in each cohort

was 38 (median=32, range=1075)

Median survival time ranged from 10.2 to 42.0
months.
For all cohorts taken together, the mean
weighted median survival time was 24.5
months.

Each 10% increase in

the proportion of
patients in each cohort
undergoing maximal
interval cytoreductive
surgery was associated
with a 1.9 month
increase in median
survival time
(95%CI=0.23 months
3.50 months, p=0.027).

Each incremental

chemotherapy cycle
was significantly
associated with a 4.1
month decrease in
median survival time
(95%CI=8.1 to 0.1
months, p=0.046).

Each 10% increase in

the proportion of
patients receiving a
taxane was associated
with a 1.6 month
increase in median
survival time (95%
CI=0.87 months2.25
months, p<0.0005)

Each 10% increase in the proportion of

patients with stage IV disease was associated

with an estimated 2.3 month decrease in
median survival time (95%CI=3.70 months
to 1.00 months, p=0.002).
No statistically significant relationship
between median cohort age and median
survival time (p=0.448).

Neoadjuvant chemotherapy in lieu of primary

cytoreduction is associated with inferior

overall survival compared to initial surgery.
Increasing percent maximal cytoreduction is
positively associated with median cohort
survival

The negative survival effect of increasing

number of chemotherapy cycles prior to

interval surgery suggests that definitive
operative intervention should be undertaken
as early in the treatment program as possible.

To compare
Primary
debulking
surgery (PDS)
followed by
platinum-based
chemotherapy

VS

Neoadjuvant
chemotherapy
(NACT) followed
by interval
debulking
surgery and
additional
chemotherapy

in advanced ovarian
carcinoma.

 Patients

Eligible patients had biopsy-proven stage IIIC

or IV invasive epithelial ovarian carcinoma,
primary peritoneal carcinoma, or fallopian-tube
carcinoma.
Study design
Patients were randomly assigned either to PDS
followed by at least six courses of platinumbased chemotherapy or to three courses of
NACT followed by interval debulking surgery

718 patients were enrolled

670 underwent
randomization
336 Were assigned to PDS
26 were
excluded
from
perprotocol
analysis

310 were included in the

per protocol analysis

334 Were assignd to

NACT
12 were
excluded
from
perprotocol
analysis

322 were included in the

per protocol analysis

The overall test for a treatment effect on global

health was not significant.

Overall survival was similar in the two groups in the

intention-to-treat analyses (29 months in the primarysurgery group and 30 months in the neoadjuvantchemotherapy group)

Progression-free survival was similar in the two groups in the

intention-to-treat analyses (12 months in both groups)

 Hazard ratio for death in the group assigned

to neoadjuvant chemotherapy followed by

interval debulking, as compared with the
group assigned to primary debulking, was
0.98 (90% confidence interval [CI], 0.84 to
1.13; P = 0.01 for noninferiority)
Hazard ratio for progressive disease was 1.01
(90% CI, 0.89 to 1.15).

Similar results for overall survival (hazard ratio for death, 1.00;
90% CI, 0.85 to 1.16; P = 0.01 for noninferiority)

PDS
(months)

NACT
(months)

No residual tumor (optimal result)

45

38

Residual tumors that measured 1 to

10 mm in diameter (suboptimal
result)

32

27

Residual tumors larger than 10 mm

(other result)

26

25

The strongest independent predictors of prolonged

survival, in descending order:
Absence of residual tumor after surgery (P<0.001);
Stage IIIC disease (P = 0.001);
Small tumor size before randomization (P = 0.001);
Endometrioid histologic type, followed in
descending order by serous, mixed,
undifferentiated, mucinous, and clear-cell types (P
= 0.005);
Younger age (P = 0.005).

The standard of care for women with stage IIIB

or earlier-stage epithelial ovarian cancer a

group with a better prognosis than the current
study population remains primary
cytoreductive surgery.
Only those patients with proven stage IIIC or
IV disease should be considered for
neoadjuvant chemotherapy.

The clinician may assess important predictive

factors with respect to residual macroscopic

disease after debulking surgery (e.g.,
presence or absence of coexisting illnesses,
age, disease burden, location of metastatic
sites, WHO performance status, and tumor
stage).
Laparoscopy, in addition to axial CT, may
provide information about the disease burden

NACT is not inferior to PDS for patients with

stage IIIC or IV ovarian carcinoma.

No significant advantages of NACT or PDS
were observed with respect to survival,
adverse effects, quality of life, or
postoperative morbidity or mortality.

To evaluate the use of neoadjuvant

chemotherapy (NACT) and primary debulking

surgery (PDS) before and after results from a
randomized trial were published and showed
noninferiority between NACT and PDS in the
management of advanced-stage ovarian
carcinoma.

Study design : retrospective analysis

Place : at Memorial Sloan Kettering Cancer

Center
Time : January 1, 2008 to May 1, 2013
Patients : all newly diagnosed patients who
presented with stage III or IV disease
according to FIGO staging criteria (586
patients)

Exclusion : if they had already undergone PDS

at an outside facility, completed NACT prior to

presentation, presented with borderline or
low-grade histology, or had stage I or II
disease
The decision to offer PDS as a primary
treatment strategy was at the discretion of
the individual surgical attending

There were no 30-day postoperative deaths in

either the PDS or NACT cohort

There were 80 (14%) grade 3 or 4 adverse
events in the entire cohort of 586 patients;
16% among the 432 patients in the PDS group
and 6% among the 154 patients in the NACT
group (p < 0.001).

PDS

NACT

Median
PFS

21.7 months
(95% CI, 19.523.8)

13.9 months
(95% CI 12.5-16.1)

Median
OS

71.7 months
(95% CI, 59.8-not
reached)

42.9 months
(95% CI, 37.156.3)

 The best survival

outcomes were observed

in patients who achieved
a complete gross
resection at the time of
PDS, although OS after
complete gross resection
at the time of IDS
(median OS,
66months)was
comparable to that for
patients left with minimal
residual disease at PDS.

In this single-institution analysis, the best

survival outcomes were observed in patients

who were deemed eligible for PDS followed by
platinum-based chemotherapy
With improved optimal resection rates and
less adverse event in NACT, they conclude
that NACT is reasonable treatment strategy
for advanced ovarian cancer.