1) Neoadjuvant chemotherapy (NACT) involves administering chemotherapy before surgery to reduce morbidity and mortality from surgery and increase the likelihood of a complete resection of disease. 2) NACT is recommended for patients with clinically unresectable epithelial ovarian cancer or those who are poor surgical candidates due to comorbidities. 3) After 3 cycles of NACT, patient response is evaluated with imaging and surgery is performed if resection is possible; if disease has progressed, further chemotherapy is recommended.

1. Advanced Ovarian Cancer : Neoadjuvant Chemotherapy
DR SUMIT KUMAR
ASSISTANT PROFESSOR
NEIGRIHMS

2. INTRODUCTION
Epithelial cancers of ovarian, fallopian tube, and peritoneal origin
exhibit similar clinical characteristics and behavior.
Approximately 75 % of women have stage III or stage IV disease at
diagnosis.
For most patients, EOC is treated surgically and followed by adjuvant
adjuvant platinum- and taxane- based chemotherapy.
However, neoadjuvant chemotherapy (NACT) prior to definitive
surgery is an alternative option in selected patients.

3. Overview And Rationale :NACT
3-4 cycles of
NACT
Imagin
g
Resectabl
e
Not
resectable
Interval
cytoreductio
n
Adj CT
Continue CT
Goal of NACT:
 Reduce perioperative morbidity and mortality
 Increase the likelihood of a complete resection of disease
Clinical studies have shown that survival is not improved with NACT
followed by surgery vs standard surgery followed by adj CT.

4. Outcomes Relative To Primary Debulking Surgery
Trial Comparative Arm Result
Cochrane Review
(1521 stage III/IV)
NACT followed by debulking surgery vs.
Primary debulking surgery followed by
chemotherapy
Similar OS HR: 0.95 (95% CI 0.84-1.07)
Four randomised trial same
PFS HR: 0.97 (95% CI 0.87-1.07),
Lower postoperative mortality,
lower infection rates, lower need for stoma
formation, and lower bowel resection
SCORPION trial
NACT followed by debulking surgery vs.
Primary debulking surgery followed by
chemotherapy
Similar results to Cochrane Review for OS
and PFS, Lower postoperative mortality,
lower infection rates, lower need for stoma
formation, and lower bowel resection
NACT also give information about chemotherapy effectiveness IN-VIVO.
IF disease is chemoresistant, its unlikely to benefit from surgery

5. PATIENT SELECTION
 Approach : NACT criteria
 Advanced EOC stage IIIC or IV , unresectable disease unlikely to become complete or optimally
cytoreduced (ie, no residual cancer or <10 mm of residual disease at the end of surgery,
respectively)
 if initially poor operative candidates, but who are likely to tolerate surgery after chemotherapy.
 if patient, unlikely to tolerate surgery at any point due to poor functional status, proceed with
chemotherapy alone.
European Organisation and Research for the Treatment of Cancer
(EORTC) 55971 trial
(stage IV patients most appropriate to undergo NACT rather than primary surgery)
 Higher 5-yr OS rates following NACT compared with primary surgery (22 vs 5 %,
respectively).
However, other markers including age, performance status, tumor grade, and histology did not suggest a benefit
from NACT vs primary surgery, or vice versa

6. Unresectable disease Definition
Most experts agree that criteria for unresectability include patients with the following:
Diffuse and/or deep infiltration of the small
bowel mesentery
Diffuse carcinomatosis involving the stomach
and/or large parts of the small or large bowel
Infiltration of the duodenum and/or parts of
the pancreas (not limited to the pancreatic
tail)
Involvement of the large vessels of the
hepatoduodenal ligament, celiac trunk, or
behind the porta hepatis
Involvement of the liver parenchyma
Lung metastases
Lymph node metastases in axilla or
mediastinum
Defining unresectable disease —baseline imaging (eg, computed tomography [CT] of the chest,
abdomen, and pelvis) to determine if the disease is resectable or not, and possible diagnostic laparoscopy

7. Role of diagnostic laparoscopy
• Diagnostic laparoscopy is crucial in assessing resectability for advanced
EOC.
• Laparoscopy indicates optimal debulking in 70-100% of cases.
• Scoring system for resectability includes:
• Peritoneal carcinomatosis
• Diaphragmatic disease
• Mesenteric disease
• Omental disease
• Bowel infiltration
• Stomach infiltration
• Liver metastases
• Scores ≥8 prompt Neoadjuvant Chemotherapy (NACT).

8. CHOICE OF REGIMEN
For women who will undergo NACT, an
initial 3 cycles of IV carboplatin plus
paclitaxel, with the addition of
bevacizumab for those with high-risk
disease (eg, pleural effusion, ascites).

9. TREATMENT EVALUATION AND SUBSEQUENT APPROACH
• Assessment During NACT
 Serial evaluations before each NACT cycle:
 Interim history and physical examination
 Complete blood count
 Serum chemistries (including liver and renal function tests)
 CA 125 measurement
• Treatment Response Assessment
• CT scan after three cycles of NACT
• Evaluation by gynecologic oncology surgeon
• Surgical Cytoreduction
• Patients without progression during NACT
• Chance of optimal cytoreduction
• Chemoresistant Disease
• Patients with disease progression or insufficient response
• Consider medical therapy
• Variability in Approach
• Experts may differ; some recommend re-evaluation for surgery in partial responders to NACT.

10. DEFINITIVE SURGICAL TREATMENT
 Surgical approach &goal after NACT— Definitive surgical cytoreduction of resecting
macroscopic tumor (preferred goal) or at least of achieving an optimal cytoreduction (ie, <10
mm residual disease),
 Heated intraperitoneal chemotherapy at surgery —optimal surgical result (ie, residual
disease <1 cm), heated intraperitoneal (IP) chemotherapy (HIPEC) at the time of
cytoreduction.

11. Randomised trial (hipec)
Outcome HIPEC Group No HIPEC Group
Overall Survival (OS) 46 months 34 months
Recurrence-Free Survival
(RFS)
14 months 11 months
Mortality Rate 50% 62%
Grade 3 or 4 Adverse Events 27% 25%
•Study Population: 245 women with stage III ovarian cancer
randomised trial
•Treatment in Both Groups: Three cycles of IV carboplatin and
paclitaxel as NACT, followed by surgery.
•HIPEC Group: Received surgery with HIPEC using cisplatin at 100
mg/m2.
•No HIPEC Group: Underwent surgery without HIPEC.
•Follow-up: Median follow-up of 4.7 years

12. Second trial (hipec)
Outcome HIPEC Group Control Group
PFS 20 months 19 months
OS 70 months 61 months
•Study Population: 184 patients with stage III or IV ovarian
cancer.
•Surgical Approach: Primary cytoreductive surgery or interval
cytoreductive surgery after NACT, with <1 cm residual tumor.
•HIPEC Group: Received HIPEC. Control Group: Did not receive
HIPEC.
•Overall Findings: Similar PFS and non-statistically significant
improvements in OS for HIPEC vs Control.
Outcome
HIPEC Group
(Interval
Cytoreduction)
Control Group
(Interval
Cytoreduction)
PFS 30 months 24 months
OS 62 months 48 months
•Subgroup Analysis:Among 77 patients
who had interval cytoreductive surgery
after NACT.
•HIPEC group had significantly improved
median PFS and OS compared to the
Control group.

13. ADJUVANT TREATMENT IN PATIENTS TREATED WITH NACT
• Number of Cycles:
• Typically, further treatment with intravenous (IV)
carboplatin and paclitaxel is offered for 3-6 cycles.
• some offer 3 cycles, while others typically administer
6, except in verified stage I/II disease.
• Intravenous (IV) vs. Intraperitoneal (IP) Treatment:
• IV therapy is commonly used due to toxicity
considerations.
• IV/IP treatment may be considered for a select gp of
patients.
• Consideration for IV/IP treatment in patients who
received NACT and underwent optimal cytoreduction.
• Rarely use IV/IP therapy for patients with extensive
extra-abdominal disease after neoadjuvant treatment.
Outcome
IV/IP
Treatment IV Treatment
Progression-
Free Survival
(PFS) at 9
Months
39% 25%
Median PFS 13 months 11 months
Median OS 59 months 38 month
Table: OV21/PETROC Trial
Results
The trial did not have sufficient power to
detect differences in median survival, and the
trends were not significant.

14. SUMMARY AND RECOMMENDATIONS
• Neoadjuvant Chemotherapy (NACT):
• Administration of systemic therapy before definitive surgery.
• Goal: Reduce perioperative morbidity, mortality, and increase likelihood of complete resection.
• Patient Selection:
• Offer NACT for clinically apparent, unresectable epithelial ovarian cancer (EOC).
• Offer NACT to EOC patients poor surgical candidates due to comorbidities but likely to tolerate surgery after
chemotherapy.
• Diagnostic Laparoscopy:
• Conduct laparoscopy for stage III or IV EOC to determine resectability.
• Choice of Chemotherapy:
• Prefer intravenous platinum-based chemotherapy for NACT.
• Preference for carboplatin plus paclitaxel, with or without bevacizumab.

15. SUMMARY AND RECOMMENDATIONS
• Assessment and Next Steps:
• Serial evaluations during NACT, including history, physical exam, CBC, serum chemistries, and CA-125
measurement.
• Evaluate treatment response after three NACT cycles.
• Surgical cytoreduction for patients with a chance of optimal resection.
• Suggest HIPEC at cytoreduction for optimal surgical results, if expertise is available.
• Medical therapy for disease progression during NACT or lack of optimal cytoreduction after three cycles.
• Treatment Following Surgery:
• Suggest adjuvant platinum-based chemotherapy post-surgery.
• Prefer IV chemotherapy over intraperitoneal therapy.
• Preference for carboplatin and paclitaxel for three to six cycles.