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Splenectomy During Secondary Cytoreduction for Ovarian

Cancer Disease Recurrence: Surgical and Survival Data
Natalina Manci, MD,1 Filippo Bellati, MD,1 Ludovico Muzii, MD,2 Marco Calcagno, MD,1
Sagit Arbel Alon, MD,1 Milena Pernice, MD,1 Roberto Angioli, MD,2 and
Pierluigi Bendetti Panici, MD1
1Department of Gynecology and Obstetrics, University of Rome ‘‘La Sapienza’’, V.le Regina Elena, 324, 001161 Rome, Italy
2Department of Obstetrics and Gynecology, Campus Bio Medico University of Rome, Rome, Italy

Background: Ovarian cancer disease recurs predominantly in the abdomen, with the spleen
usually involved as part of a vast spread of upper-abdominal disease or, less frequently, as an
isolated site of disease recurrence. Very few reports are available in the literature on the
outcome of patients subjected to splenectomy during secondary cytoreduction. The aim of this
study was to identify prognostic factors and to review surgical and clinical data in order to
identify those patients who would benefit the most from splenectomy during secondary
cytoreduction.


Methods: This was a retrospective review of platinum-sensitive recurrent epithelial ovarian
cancer patients who underwent splenectomy as part of secondary cytoreduction. Surgical and
survival data were recorded.
Results: Twenty-four patients were identified. Multiple site disease recurrence was observed
in 15 patients. The spleen was involved at the hilus in 12 patients; surface and intraparenchymal
metastases were equally present. Optimal cytoreduction was achieved in all patients.
At a median follow-up of 30 months, median progression-free and overall survival from the
time of secondary surgery were 34 and 56 months, respectively. Overall survival was significantly
correlated to residual disease at secondary surgery, disease-free survival, consolidation
chemotherapy, and type of adjuvant therapy.
Conclusions: Splenectomy as part of secondary cytoreduction is a feasible and safe procedure.
Secondary cytoreduction in selected groups of patients is confirmed to be associated with
high long-term survival rates even when aggressive surgery of the upper abdomen is required.
Key Words: Ovarian cancer recurrence—Secondary cytoreduction—Splenectomy.
Ovarian cancer is the primary cause of death for
gynecologic malignancies in industrialized countries.1
First-line treatment includes cytoreductive surgery
and platinum-based chemotherapy.2,3 More than
one-half of the patients treated with first-line chemotherapy
achieve a clinical complete response, but
only a one-quarter will benefit from long-term disease
remission.4 To date, no unanimous consensus has
been reached on the strategy that should be adopted
in recurrent patients. Possible strategies include second-
line chemotherapy5 or secondary cytoreduction.6
Secondary cytoreduction frequently requires aggressive
surgical procedures that are inevitably associated
with significant intra- and postoperative morbidities.
In the paucity of literature data, physicians are
required to carefully tailor treatment strategies on the
basis of patients characteristics and prognostic
factors.
The recurrence of ovarian cancer disease involves
the abdomen in most cases.7 The spleen is usually
Received August 26, 2005; accepted February 15, 2006;
published online September 7, 2006.
Address correspondence and reprint requests to: Natalina
Manci, MD; E-mail: natalina.manci@uniroma1.it.
Published by Springer Science+Business Media, Inc. 2006 The Society of
Surgical Oncology, Inc.
operative data are reported in Table 2. At surgery,
15 patients (62%) were found to have more than a
single lesion. The largest spleen lesion was at the
hilus (12 patients, 50%). Intraparenchymal and
superficial spleen involvement were equally present
in six patients (25%). Intraparenchymal lesions were
always found as a solitary lesion, whereas hilar and
superficial spleen involvements were mostly found
as part of multiple-site disease recurrence. Carcinomatosis
was present in most patients with multiple
lesions (11 cases, 73%). The most frequently
encountered extrasplenic lesions were on the bowel
and on the pelvic/abdominal wall. Major associated
procedures, in addition to splenectomy, were carried
out in 16 patients (67%) and included: extensive
stripping (diaphragmatic and bilaterally
paracolic gutter) or argon beam coagulation (11
patients, 46%), large bowel resection (5 patients,
21%), small bowel resection (two patients, 8%),
distal pancreatectomy (four patients, 17%), partial
hepatectomy (two patients, 8%), lymphadenectomy
(two patients, 8%), and partial gastrectomy (one
patient, 4%). One bowel resection and all pancreatectomies
were performed for technical surgical
reasons or to achieve optimal debulking in the
spleen hilar region and not for direct organ
involvement (Fig. 2). Median operative time was
155 minutes (range: 50 480). Median estimated
blood loss was 610 ml (range: 320 1800 ml). As
expected, both operative time and estimated blood
loss were significantly greater in patients affected by
multiple lesions than in patients with solitary disease
recurrence (P = 0.008, P = 0.004, respectively).
Five patients (21%) required blood
transfusions and five patients (21%) had intraoperative
hemorrhage with blood loss of more than
1000 ml (range: 1100 1800). No other major intraoperative
complications were reported. Major
postoperative complications were early postoperative
small bowel obstruction (one patient, 4%),
pulmonary embolism (one patient, 4%), and a
pancreatic fistula (one patient, 4%). All patients
were treated conservatively and no reoperation was
performed. Median postoperative hospital stay was
6 days (range: 3 13 days).
All patients received vaccination for S. pneumoniae,
H. influentiale, and N. meningitides, and no episode of
sepsis was registered during the follow-up period.
Splenectomy was performed at the end of the
surgical procedure or after having assessed the
possibility of achieving optimal cytoreduction and,
as expected, all patients benefited from optimal
cytoreduction; in addition, 16 patients (67%) had nothe presence of normal CA-125 values and a negative
CT scan (Fig. 1). Seven patients (29%) had a preoperative
diagnosis of multiple lesions. In none of the
patients was carcinomatosis suspected preoperatively.
Surgical Findings
All patients were subjected to diagnostic laparoscopy
before laparotomy. Surgical findings andwere alive with clinical evidence of disease after a
median time of 32 months (range: 22 45 months),
and seven patients died of disease after a median time
of 21 months (range: 5 56 months). Median progression-
free and overall survival from secondary
surgery were 34 and 56 months, respectively (Fig. 3).
All six patients with isolated intraparenchymal
spleen recurrence were alive and disease-free with the
writing of this article (median follow-up: 27.5, range:
11 100 months).
Survival rate was significantly longer in patients
who were completely cytoreduced (RT = 0) than in
those who were not (estimated 3-year OS: 91 vs. 62.5%,
P = 0.002). Moreover, survival rate was significantly
related to DFI (>12 months vs. £12 months; estimated
3-year OS: 100 vs. 50%, P = 0.002), consolidation
chemotherapy (no consolidation vs.
intraperitoneal paclitaxel; estimated 3-year OS: 100 vs.
65%, P = 0.003), and chemotherapy after splenectomy
(platinum-based vs. non-platinum based; estimated
3-year OS: 100 vs. 51%, P = 0.03). Age,Survival Data
Of the 24 patients identified (median follow-up: 30
months; range: 5 100 months), 13 patients were still
alive with no evidence of disease after a median time
of 33 months (range: 9 100 months), four patientsresidual disease at primary surgery, CA-125, number
of lesions, and carcinomatosis did not alter the
survival rates significantly.
CONCLUSIONS
Splenectomy during secondary cytoreduction
appears to be a feasible and safe procedure and may
be associated with long-term survival. It should be
noted that the patients analyzed in this report represent
a subgroup of patients with a long disease-free
interval and chemotherapy-responding tumors and
who had achieved optimal residual disease at primary
surgery. In addition, splenectomy during secondary
surgery was performed only in patients who were
judged to be optimally cytoreducible at laparoscopy.
As expected, surgical difficulty, using operative
time and estimated blood loss as surrogate markers,
was significantly greater for patients with multiple
lesions than with patients affected by solitary lesions.
The severe perioperative complication rate was low in
both groups. Unfortunately, a high proportion (8/17,
47%) of those patients with preoperative diagnosis of
solitary lesions were found to have multiple lesions
and, therefore, it was not possible to determine surgical
difficulty preoperatively; this development
highlights the necessity for such patients to be treated
in referral oncology centers.
Survival rate was affected by residual tumor at
secondary cytoreduction (0 vs. 0.5 cm), DFI (<12 br="">months vs. >12 months), consolidation chemotherapy
(no consolidation vs. intraperitoneal paclitaxel),
and adjuvant chemotherapy after splenectomy (platinum-
based vs. non-platinum-based chemotherapy).
The prognostic relevance of RT,6,12 DFI,13 and type
of chemotherapy14 has already been described in
previous reports. Consolidation chemotherapy
has been demonstrated to improve progression-free
survival in phase III trials.15 It is possible that the
negative association between consolidation chemotherapy
and survival in the present report was caused
by a physician bias that resulted, at the end of standard
adjuvant chemotherapy, in only patients with
negative prognostic factors (i.e., residual tumor, histotype,
tumor grading) being treated with intraperitoneal
paclitaxel. In the present series, however, we
were unable to identify such factors, although the
retrospective nature of the trial does not allow us to
exclude completely this hypothesis. An alternative
hypothesis is that micrometastases that persist after
intraperitoneal paclitaxel are biologically more
aggressive.
Spleen involvement in ovarian cancer has been
reported to be as high as 20%16. The spleen can be
involved either as a solitary lesion,10,11 or, more
frequently, as part of extensive carcinomatosis of
the upper abdomen. Only a small number of trials
9,11,17 31have addressed the issue of splenectomy
during ovarian cancer surgery, and only a few of these
have included patients being subjected to secondary
cytoreduction.9,17,20,23,25,27,30
Deppe et al.17 reported the first case of splenectomy
during secondary cytoreduction in a patient
who had benefited from a 5-year DFI. This patient
was disease free after 1 year of follow-up; however,
no further information is available on the longer
follow-up. Morris et al.20 analyzed the indications
and complications associated with splenectomy in 45
patients. In their study, 24 patients underwent splenectomy
during ovarian cancer cytoreduction, 15 of
whom as secondary cytoreduction. The overall complication
rate was 29% with one postoperative death.
Nicklin et al.23 reported results obtained in 18 patients
who had been subjected to splenectomy during
surgical cytoreduction, with 11, one, one, and five
patients undergoing a splenectomy during primary
cytoreduction, interval debulking surgery, secondlook
laparotomy, and secondary cytoreduction,
respectively. Four patients of the latter group were
affected by recurrent ovarian cancer, whereas the
remaining patient was affected by fallopian tube
cancer. Splenectomy was performed in 13 cases for
parenchymal, hilar, or capsular disease. Residual
disease was £5 mm in ten patients. Intraoperative
complications included pancreatic tail lesions in four
cases. The mean operating time was 368 minutes
(range: 180 560 minutes), and mean estimated blood
loss was 1578 (400 2800) ml. Of the 18 patients
undergoing this procedure, 11 had died of disease at a
median time of 12.0 months postoperatively (range:
5 59.5 months); five patients were alive with disease
at a median time of 8 months postoperatively (range:
2 16 months); two patients were alive with no clinical
evidence of disease at 2.5 months of follow-up.
When the patients of our series are compared to those
of Nicklin et al., our achievement of optimal residual
disease and survival data would appear to be superior.
In addition, the surgical time and blood loss
reported by Nickin et al. appear to be higher (mean
operative time and mean operative blood loss in the
present series were 180 ± 108 minutes and
735 ± 401ml, respectively). This large discrepancy
between our results and those reported by Nicklin
et al. is likely due to the completely different study
cohorts in these studies; in fact, only five out of the 18ml, respectively. The median postoperative stay was
6 days (4 9 days). It would seem that the increase in
surgical time obtained in the series reported by Chi
et al. is a minor disadvantage when compared with
the significant decrease in blood loss and postoperative
stay. If, as the authors stated, these results will be
confirmed in larger series, it is hopeful that laparoscopy
or hand-assisted laparoscopy will become
standard surgery carried out in such patients.
In conclusion, splenectomy during secondary
cytoreduction is a feasible and safe procedure. This
analysis confirms that patients affected by isolated
intraparenchymal lesions benefit from long-term
disease-free survival. Selected patients may benefit
from secondary cytoreduction even when aggressive
surgery of the upper abdomen is required.
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