This document discusses staging, treatment, and survival rates for ovarian cancer. It notes that over 70% of patients present with advanced stage III or IV disease, and less than 40% of women are cured. Primary treatment consists of surgical staging and cytoreduction followed by chemotherapy. Platinum-based chemotherapy, particularly carboplatin and paclitaxel, is now the standard first-line treatment and has improved progression-free and overall survival rates compared to previous single agents or regimens. Adjuvant chemotherapy is also now recommended for early stage high risk disease to further reduce relapse rates.

1. Early stage ovarian cancer

2. Stage and survival

3.  More than 70% of patients present with advanced
disease.
 Only less than 40% of women with ovarian cancer
are cured.

4. Early stage
 Stage 1 and 2
 Low risk- stage 1a n 1b with grade 1 n 2
 High risk- stage 1c, stage 1 with grade 3 and stage 2
 Advanced stage- stage 3 n 4

5. Treatment
 Primary treatment for presumed ovarian cancer
consists of appropriate surgical staging and
cytoreduction,
 followed in most (but not all) patients by systemic
chemotherapy

6. STAGING LAPAROTOMY

7.  It is recommended that a gynecologic oncologist
perform the surgery.
 a vertical midline abdominal incision should be used
 On entering the abdomen, aspiration of ascites or
peritoneal lavage should be performed for peritoneal
cytologic examinations
 All peritoneal surfaces should be visualized, and any
peritoneal surface or adhesion suspicious for
harboring metastasis should be selectively excised
or biopsied.

8.  In the absence of any suspicious areas, random
peritoneal biopsies should be taken from
 the cul de sac, pelvic side walls, paracolic gutters,
and undersurfaces of the diaphragm (diaphragm
scraping for Papanicolaou stain is an acceptable
alternative).
 Bilateral salpingo-oophorectomy (BSO) and
hysterectomy should be performed with every effort
to keep an encapsulated mass intact during removal.
 Infracolic omentectomy

9. Lymph node dissection
 Para-aortic lymph node dissection should be performed
by stripping the nodal tissue
 from the vena cava and the aorta bilaterally to at least the
level of the inferior mesenteric artery and preferably to
the level of the renal vessels.
 The preferred method of dissecting pelvic lymph nodes is
bilateral removal of lymph nodes overlying and
anterolateral to the common iliac vessel, overlying and
medial to the external iliac, overlying and medial to the
hypogastric vessels, and from the obturator fossa at a
minimum anterior to the obturator nerve

10. Mucinous tumors
 Primary invasive mucinous tumors of the ovary are
uncommon. Thus, the upper and lower GI tract
should be carefully evaluated to rule out an occult GI
primary with ovarian metastases
 an appendectomy should be performed in patients
with a mucinous ovarian neoplasm.

11. Fertility sparing surgery
 A unilateral salpingo-oophorectomy (USO)
(preserving the uterus and contralateral ovary) may
be adequate for select stage I tumors (stage 1A and
1C, but not stage 1B)
 and/or low-risk ovarian tumors (ie, early-stage, low-
grade invasive tumors; ovarian LMP tumors).
 Comprehensive surgical staging should still be
performed to rule out occult higher-stage disease

12. Cytoreductive Surgery
 Cytoreductive surgery is the initial treatment
recommendation for patients with clinical stage II, III,
or IV disease
 A maximal effort should be made to remove all gross
disease
 Surgical cytoreduction is optimal if the residual tumor
nodules are less than 1 cm in maximum diameter or
thickness

13. Role of chemotherapy
 Adjuvant
 Neoadjuvant

14. Evolution of chemotherapy in carcinoma
ovary
 Similar to other malignancies, the management of
ovarian cancer has evolved from single agent to
combination chemotherapy
 Some of the first drugs used in ovarian cancer
included single agent alkylating agents like
melphelan, chlorambucil, cyclophpsphomide
 This was the available agents till 1970s
 Their response rate was very low 10-25%

15.  Subsequently, clinical trials performed in the late
1970s demonstrated that cisplatin was an active
chemotherapy in advanced or recurrent ovarian
cancer with a single agent response rate in the
range of 13–30% [Rossof et al. 1979; Thigpen et al.
1979].
 Numbers of complete responses and overall
response rates doubled compared with earlier single
agent trials of non-platinum drugs
 Subsequently, cisplatin became the primary
chemotherapeutic agent defining the comparison
arms for many clinical trials in ovarian cancer

16. Role of combination
 The next generation of research studies evaluating
combination chemotherapy with cisplatin plus
cyclophosphamide revealed that the time to
progression and the duration of survival were
markedly improved compared with single agents
[Decker et al. 1982].

17. Triplets added benefit?
 Adding doxorubicin to the cyclophosphamide plus
cisplatin doublet in women with optimally debulked
stage III ovarian carcinoma
 did not result in improved progression-free survival
(PFS) (median, 22.7 months and 24.6 months) or
OS (median, 31.2 months and 38.9 months) [Omura
et al. 1989]
 As a result, the standard combination chemotherapy
in the late 1980s and early 1990s was cisplatin plus
cyclophosphamide

18. Introduction of carboplatin
 Carboplatin was introduced in the 1990s as an
analog of cisplatin with similar single-agent activity in
terms of response and survival rates, but with a
significantly improved toxicity profile
 The lower incidence of emesis, sensory neuropathy,
oto- and nephrotoxicity favored carboplatin
 however, myelosuppression was increased
compared with cisplatin.

19. Carboplatin vs cisplatin
 Alberts and colleagues conducted a phase III
randomized trial in stage III (suboptimal) and stage
IV ovarian cancer, comparing
cisplatin/cyclophosphamide versus
carboplatin/cyclophosphamide [Alberts et al. 1992].
 Both arms demonstrated a similar OS (17.4 and 20.0
months for the cisplatin and carboplatin study arms,
respectively) and similar response rates including
pathologic complete responses.
 The regimen of carboplatin/cyclophosphamide had a
significantly better therapeutic index compared with
standard cisplatin/cyclophosphamide.

20.  Multiple randomized studies conducted in advanced
ovarian cancer and a meta-analysis of these studies
confirmed that carboplatin (given as single agent or
in combination regimens) had similar survival rates
compared with cisplatin [Aabo et al. 1991], alone or
in combination

21. Introduction of taxanes
 Paclitaxel introduced in 1990s
 The GOG study- randomized 410 women with
suboptimally debulked ovarian cancer to cisplatin (75
mg/m2) plus either cyclophosphamide (750 mg/m2)
or paclitaxel (135 mg/m2 over 24 h).
 The response rate (73 versus 60%, p = 0.01)
 PFS (18 versus 13 months, p<0.001)
 OS (38 versus 24 months, p<0.001) all favored the
cisplatin/paclitaxel arm [McGuire et al. 1996]

22.  The second study was an intergroup European and
Canadian randomized clinical trial with broader
selection criteria compared with the GOG study.
 In addition, paclitaxel was delivered as a 3-h rather
than a 24-h infusion.
 This study demonstrated an improved outcome in
the paclitaxel group compared with the
cyclophosphamide group [Piccart et al. 2000].
 This benefit in survival (35.6 versus 25.8 months, p =
0.0016) was seen despite the fact that the study
allowed crossover from the cyclophosphamide arm
to the paclitaxel arm at progression.

23. PACLI/CISPLATIN VS PACLI/CARBO
 A non-inferiority trial conducted by the GOG in
patients with optimally debulked stage III ovarian
cancer
 randomized 792 patients to cisplatin 75 mg/m2 plus
paclitaxel 135 mg/m2 over 24 h, or carboplatin area
under curve (AUC) = 7.5 plus paclitaxel 175 mg/m2
over 3 h [Ozols et al. 2003].
 The median PFS and OS were 19.4 and 48.7
months, respectively, for the cisplatin arm compared
with 20.7 and 57.4 months, respectively, for the
carboplatin arm.

24.  The study met its primary non-inferiority end-point
 the carboplatin arm was easier to administer and
better tolerated compared with the cisplatin arm.
 Similar results were seen by du Bois and colleagues
in a phase III non-inferiority trial comparing paclitaxel
plus cisplatin with paclitaxel plus carboplatin in
patients with advanced ovarian cancer [du Bois et al.
2003].

25. Docetaxel
 Scottish Randomized Trial in Ovarian Cancer (SCOTROC1),
compared docetaxel/carboplatin with paclitaxel/carboplatin as initial
chemotherapy for stage IC–IV ovarian and/or primary peritoneal
cancers [Vasey et al. 2004].
 The PFS, which was the primary end-point of the study, was similar
in both groups (15.0 months versus 14.8 months p = 0.707).
 The OS rates at 2 years were comparable in both arms.
 More grade 3–4 neutropenia was associated with docetaxel while
increased grade 2 or higher neurotoxicity was reported with
paclitaxel.
 So docetaxel plus carboplatin represents an alternative first-line
chemotherapy regimen for patients with newly diagnosed ovarian
cancer.

26.  Further attempts to improve the efficacy of the standard
platinum/paclitaxel regimen by utilizing various triplet or
sequential doublet chemotherapy failed to demonstrate
improved outcomes in patients with advanced ovarian
cancer [Bookman et al. 2009]
 The Gynecologic Cancer Intergroup randomized 4312
women with stages III or IV ovarian cancer to a five-arm
trial.
 The reference carboplatin/paclitaxel arm was compared
with the investigational arms
 that incorporated gemcitabine, liposomal doxorubicin, or
topotecan given concurrently or sequentially with
carboplatin/paclitaxel

27.  Each arm received at least four cycles of standard
carboplatin/paclitaxel.
 The primary end-point of this study was OS.
 All arms had similar PFS and OS values.
 This series of randomized phase III studies
established carboplatin/paclitaxel as the standard
chemotherapy regimen

28. Adjuvant chemotherapy in early stage
 Patients with grade 3 tumors and extension beyond
the ovarian capsule or into the abdominal wall or
peritoneum (stage IC or II) demonstrated a relapse
rate of 20%
 two randomized European trials
 International Collaborative Ovarian Neoplasm Trial 1
[ICON-1]
 Adjuvant ChemoTherapy in Ovarian Neoplasm Trial
[ACTION]

29.  compared platinum-based adjuvant chemotherapy
with observation following surgery in early-stage
ovarian cancer.
 Overall survival at 5 years was 82% in the
chemotherapy arm and 74% in the observation arm
 Such patients include those with stage I, grade 3,
stage IC, or any stage II disease
 although subset analysis revealed that the benefit
appeared to be restricted to those patients who did
not undergo adequate surgical staging

30. Adjuvant chemotherapy
 Observation in patients with stage IA or IB, grade 1
tumors
 because survival is greater than 90% for this group
with surgical treatment alone
 Stage 1A or 1B grade 2 observation/ chemotherapy
 Stage 1A or 1B grade 3, stage 1C n above need
adjuvant chemotherapy

31. How many cycles of chemotherapy?
 GOG study -3 vs 6 cycles of pacli/carbo
 The relapse rate and progression-free survival were
not statistically different between these two
treatment arms
 33% reduction in the risk of recurrence in patients
who received six cycles compared to three cycles
 administration of six cycles of adjuvant carboplatin
plus paclitaxel chemotherapy can still be considered
a reasonable approach for high-risk, early stage
patients

32. Adjuvant chemotherapy
 Intravenous chemotherapy- stage 1 and 2
 Intraperitoneal/iv chemotherapy- optimally debulked
stage 3 disease
 Its role in stage 2 controversial

33.  For earlier-stage disease recommended cycles are 3
to 6
 For patients with advanced-stage disease 6 to 8
cycles of chemotherapy are recommended

34. PRIMARY CHEMOTHERAPY/PRIMARY ADJUVANT
THERAPY REGIMENS
 Paclitaxel 175 mg/m2 IV over 3 hours followed by
carboplatin4 AUC 5-7.5 IV over 1 hour Day 1. Repeat
every 3 weeks x 6 cycles. (category 1)
 Dose-dense paclitaxel 80 mg/m2 IV over 1 hour Days 1,
8, and 15 and carboplatin4 AUC 6 IV over 1 hour Day 1.
Repeat every 3 weeks x 6 cycles. (category 1)
 Docetaxel 60-75 mg/m2 IV over 1 hour followed by
carboplatin4 AUC 5-6 IV over 1 hour Day 1. Repeat every
3 weeks x 6 cycles. (category 1)

35. PRIMARY CHEMOTHERAPY/PRIMARY ADJUVANT
THERAPY REGIMENS FOR STAGE II-IV
 Intraperitoneal (IP)/Intravenous (IV) Regimen
 Paclitaxel 135 mg/m2 IV continuous infusion over 3
or 24 h Day 1
 Cisplatin 75-100 mg/m2 IP, Day 2
 Paclitaxel 60 mg/m2 IP Day 8.
 Repeat every 3 weeks x 6 cycles. (category 1)

36.  These regimens have different toxicity profiles.
 The docetaxel/carboplatin regimen is associated with
increased risk for neutropenia
 Intravenous paclitaxel/carboplatin regimen is
associated with sensory peripheral neuropathy
 dose-dense paclitaxel is associated with increased
anemia
 The IP paclitaxel/cisplatin regimen is associated with
leukopenia, infection, fatigue, renal toxicity,
abdominal discomfort, and neurotoxicity

37. Postoperative Radiation Therapy
 The role of radiation therapy in the treatment of
patients with primary ovarian cancer has changed
markedly over time
 Because the entire peritoneal cavity is at risk for
metastatic dissemination, the radiation treatment
technique must encompass the whole peritoneum
 IP Isotopes or WAR

38. EBRT
 Princess Margaret Hospital in Toronto and GOG
compared pelvic radiation with observation or single-
agent chemotherapy (melphalan)
 Pelvic failures were reduced in those receiving
radiotherapy.
 However, upper abdominal recurrence was a major
contributor to overall recurrence
 survival was statistically similar among the three arms
evaluated.
 This suggested that ovarian cancer is responsive to
radiation, but to be effective, the treatment field needs to
include the entire abdominopelvic cavity.

39. WAR
 which is given by the open-field technique via
anterior and posterior ports shaped to encompass
the entire peritoneal cavity as well as pelvic and
paraaortic lymph nodes
 Radiation can permanently eradicate ovarian
epithelial tumors
 But tumoricidal dose depend on size

40.  Schray and associates reported pelvic irradiation of
50Gy
 < 2 cm- LR was 16%
 > 2cm – LR was 45%
 This data suggest that for large tumors tumoricidal
dose exceeds 50-60 Gy
 < 2 cm may be 45-50Gy
 For microscopic disease it may be lower

41. WAR Trials..

43.  The data indicate that when whole abdominal fields are
used, the limited tolerance of the liver, kidneys, and
spinal cord would practically rule out eradication of visible
tumor masses in the upper abdomen, regardless of tumor
size.
 For pelvic fields, the tolerance of the intestines, rectum,
and bladder would restrict the delivery of tumoricidal
doses to tumors of less than 2 cm in size.
 This analysis suggests that only patients with minimal or
microscopic residua would be candidates for cure by
radiotherapy.

44. Chemotherapy versus Radiation
 Currently, the only completed phase III trials in the
literature comparing abdominopelvic radiation with
chemotherapy have used single-agent non-platinum-
containing regimen
 attempts to complete phase III trials of
abdominopelvic irradiation and platinum-containing
standard regimens have been unsuccessful because
of poor patient accrual

46. Whole Abdominal Radiotherapy as
Consolidation Therapy
 40% to 60% of patients achieving a pathologic
complete response after chemotherapy ultimately
recur
 unrecognized microscopic residual disease has been
implicated most often
 Two recent trials Austria and norway
 Stage 3 disease with complete response after
adjuvant chemo WAR or observation

47.  WAR was associated with improved PFS but no OS
advantage

48. Treatment fields
 Encompass the whole of abdominal cavity
 WAR is given either by open field technique or by moving
strip technique
 Open field technique- anterior and posterior port shaped
to encompass the entire peritoneal cavity
 Superiorly- above the domes of diaphragm
 Inferiorly -below the obturator foramen
 Laterally beyond the peritoneal reflection

50.  The total dose- 30 Gy in 20 fractions
 1.2-1.5Gy per day
 Kidneys are shielded at 20Gy
 Liver at 25Gy
 Paraaortic – additional 15Gy
 Pelvis- additional 20-25 Gy

51. Moving strip technique
 Developed in an era in which radiation therapy
equipment could not adequately encompass the
entire abdomen in a single portal.
 The patient's abdomen was marked with 12 to 14
“strips,” each 2.5 cm in height
 4 strips are treated at a time
 This hypofractionation technique delivered daily
fractions of 225 to 300 cGy, accumulating in total
abdomen doses of 2250 to 3000 cGy..

53.  The kidneys and liver are usually shielded by partial
thickness lead blocks to restrict the dose to 15 Gy
 Additional dose of 20Gy in 10 fractions is given to
pelvis

54. Martinez technique

55.  Open field technique was preferred
 As a matter of convenience, treatment time,
technical ease
 possible reduction in late (chronic) effects

56. toxicity

57. Late toxicity

58. RADIOISOTPOES
 The radioisotope most commonly used for treating ovarian
cancer is phosphorus-32 (32P) in the form of chromic
phosphate colloid (32P-CP).
 The 32P isotope is a pure beta emitter and has a half-life of
14.3 days.
 Its beta particles have a mean energy of 0.69 Mev and tissue
penetration of 3 to 5 mm.
 The fact that there is no gamma emission provides significant
safety to the treating staff.
 The standard dose of 32P is 15 mCi given in a single IP

59.  Several prospective randomized trials have looked at 32P
versus chemotherapy, and all have shown equivalent
survival rates
 GOG trial randomized 205 patients with stage I to IIA
(high risk) to 15 mCi intraperitoneal 32P versus 3 cycles of
cyclophosphamide and cisplatin.
 With a median follow-up of 6 years, there was no
statistically significant difference in overall 5-year survival
rates (84% chemotherapy arm versus 76% 32P arm).
 The authors concluded that chemotherapy is better
because of the better progression-free interval

60. NCCN GUIDELINES

62. Prognostic factors
 FIGO stage
 volume of residual disease after cytoreductive
surgery
 histological subtype
 histological grade
 Age
 malignant ascites