8. Surgery and IP/HIPEC chemotherapy for recurrent ovarian cancer

The Cochrane review on the use of intraperitoneal (ip) chemotherapy for primary OC [58] concluded that this treatment prolonged PFS and OS. While there is evidence of a survival benefit for IP chemotherapy/HIPEC after cytoreductive surgery in primary disease, there are fewer reports on its use and efficacy in recurrent disease [59]. No mention was made of this type of treatment in the Cochrane review on recurrent ovarian cancer [60] nor in the review by the Fifth Ovarian cancer Consensus Conference of the Gynecologic Cancer InterGroup [7].

Boisen et al. [61] reported on a retrospective study of 25 patients treated with iv/ip chemotherapy but without secondary cytoreductive surgery. The study period was over 6 years on a selected group of patients and 10 of 25 had an improved treatment-free interval. In a feasibility study of ip chemotherapy in 56 patients with platinum-sensitive recurrent disease all of whom had had prior secondary cytoreductive surgery (67.9% to <1 cm), 79% tolerated 6 cycles of ip platinum. No difference in outcome was noted related to the completeness of secondary surgery and the median overall survival was 51 months; no clinical factors associated with improved PFS or OS were identified [62]. The data from other studies report that the main indicators for response to ip chemotherapy are (1) volume of residual disease and (2) platinumsensitive disease [63, 64]. Fujiwara, in contrast reported responses in patients with suboptimal surgical resection [65].

Ansaloni et al. [66] provided one of the first reports on HIPEC following cytoreductive surgery in 30 patients with recurrent disease. In this small study, HIPEC was considered safe and there was a trend to improved survival with complete cytoreduction and HIPEC. A more recent study [67] reported a survival benefit in what they described as randomised trial on the use of HIPEC in recurrent ovarian cancer. However, there were a number of deficiencies in study design and questions were raised about the validity of the results and the efficacy of HIPEC as reported in that study [68]. In another retrospective review [69], Cripe et al. reported on 32 patients that CRS and HIPEC were feasible. However, they also noted 65.6% grade 3 or 4 toxicity (morbidity) and that troublesome pleural effusions were associated with diaphragmatic stripping and/or resection. As a number of chemotherapeutic agents were used with varying dwell times and temperatures, it is unclear what regimen to recommend. As with primary disease, a key component in the use of HIPEC is complete cytoreduction or minimal residual disease (<5 mm deposits). A recent report on a retrospective cases series from China on 46 patients with advanced (n = 16) or recurrent (n = 30) ovarian cancer reported a survival benefit with HIPEC but only when there was complete surgical cytoreduction [70]. However, the adjuvant treatment included iv/ip chemotherapy and it is not clear what contribution HIPEC and ip chemotherapy made to improved survival. In contrast, in a study on secondary cytoreductive surgery in EOC, 50 patients underwent surgery only and 29 also had HIPEC, although there were no deaths in the latter group and two in the former group, the addition on HIPEC did not confer an advantage on median disease-free survival [71]. Data were not presented, however, on overall survival or disease-specific survival. In a larger retrospective multi-centre Italian study on 226 patients with primary ovarian cancer and 285 with ROC treated over 16 years, HIPEC was of benefit in patients with ROC who had had complete surgical resection and platinum-sensitive disease [72]. In a large French study of HIPEC in primary and recurrent ovarian cancer, no difference was noted in overall survival between patients with platinum-sensitive and platinum-resistant disease and the main prognostic factor for survival and DFI was the extent of disease, or tumour burden, as measured on the peritoneal cancer index [73]. In the studies showing benefit of CSC and HIPEC, it is still unclear what, if any, additional benefit HIPEC can achieve over CSC. There is still ongoing debate about the role of HIPEC, with the view that HIPEC should be offered only in clinical trials [74]. In fact a number of trials of ip chemo and HIPEC in recurrent ovarian cancer are recruiting [75].

presence of metastatic disease at other sites. In assessing the role of specialised surgery for recurrent metastatic ovarian cancer, factors to be considered include—morbidity of surgery, likelihood of resecting disease, likelihood of palliating symptoms by surgical resection, and the patient's prognosis, with and without surgery. There is also some evidence that patients treated with IP chemotherapy and then subsequently with bevacizumab have a greater propensity to develop unusual sites of metastastic recurrence [80]. Patients with a BRCA mutation compared to those who do not have a BRCA mutation more often develop unusual sites of

Surgery for Recurrent Ovarian Cancer http://dx.doi.org/10.5772/intechopen.71587 285

Most patients with EOC present with advanced stage disease and most will develop recurrence. A common presentation of recurrent disease is relapsing and remitting bowel obstruction, the course of which is more often chronic than acute [81, 82]. Invariably the development of bowel obstruction indicates recurrent (or progressive) disease, even if the tumour markers are not elevated and there is no radiological evidence of disease. The management is conservative, at least initially with fasting, intravenous fluids and pharmacological manipulation [81, 82]. Involvement of the palliative care team is important. Surgical intervention is associated with significant morbidity and mortality and not all patients, perhaps only about two-thirds benefit from surgery in terms of resumption of adequate oral intake. Despite this common problem in recurrent ovarian cancer, QoL data on surgical and non-surgical intervention are

Surgical intervention includes—placement of a gastrostomy tube [83], by pass procedures, but most often formation of a diverting stoma. As the disease is often more extensive in the pelvis with serosal and mesenteric disease, more often an ileostomy is raised rather than a colostomy, although often when a loop ileostomy is performed it is necessary to defunction the large bowel by raising a mucous fistula. If a recto-vaginal fistula develops from extensive pelvic disease, a colostomy may provide successful palliation but typically to a limited extent. That is, the patient will continue to have other problems related to the pelvic disease—including pelvic pain, discharge and vaginal or rectal bleeding. It is important to discuss with the patient the likely palliative benefit of surgery, as it is to discuss the outcomes from the surgical and non-

There are fewer reports on the role of surgery for second, third, etc. relapse of EOC. Intuitively the factors that are important in surgical decision making for first recurrence should also be important in surgical decision making in patients with second and subsequent recurrence. It is clear too that if surgery is contemplated for such relapses the patients are highly selected and more often than not surgical intervention will be for palliation (e.g. bowel obstruction) rather than for complete cytoreduction. More usually in clinical practice patients with second and

10. Recurrent ovarian cancer and bowel obstruction

recurrence.

notably absent from most reports.

surgical management of bowel obstruction.

11. Surgery for second recurrence and beyond

#### 9. Recurrent ovarian cancer outside the abdomen and pelvis

With the improvement in overall survival in ovarian cancer, and better understanding of cancer genetics, targeted therapies and improved surgery, it is now more common to see patients with unusual or atypical sites of recurrent disease [76]. Sites include breast, brain, bone (including vertebral spine), chest wall, skin (other than port site metastasis) and lymph nodes such as the axillary nodes [77–79]. Given the unusual location of metastasis it is important to exclude other sites of disease and commonly PET-CT is used. Biopsy is often necessary to exclude another cancer. In contrast, histologic confirmation of recurrent OC in the pelvis and/or abdomen is not usual clinical practice. Management of the recurrence will include general supportive measures such as pain relief, radiotherapy (e.g. with vertebral metastasis) and chemotherapy, trial drugs and specialised surgery, for example, neurosurgery. The surgery may be indicated for symptom relief and may be considered necessary, even life-saving, in the presence of metastatic disease at other sites. In assessing the role of specialised surgery for recurrent metastatic ovarian cancer, factors to be considered include—morbidity of surgery, likelihood of resecting disease, likelihood of palliating symptoms by surgical resection, and the patient's prognosis, with and without surgery. There is also some evidence that patients treated with IP chemotherapy and then subsequently with bevacizumab have a greater propensity to develop unusual sites of metastastic recurrence [80]. Patients with a BRCA mutation compared to those who do not have a BRCA mutation more often develop unusual sites of recurrence.
