6. Predictors of optimal cytoreduction

contributed to the less than expected overall survival. Indeed only 56% of patients received combination chemotherapy in their first cycle if their PS was 2–3 but this increased to 72% if their PS was 0–1. This differential has been recognised in the design of the currently recruiting

Indeed only 77% in the PDS and 79% in the NACT arms completed the allocated treatment

Both EORTC 55971 and CHORUS trials have been heavily criticised [23, 24]. Indeed one would have to question the rigour with which the peritoneal residual disease might have been assessed in these two studies. For instance the incidence of peritoneal disease within the omental bursa is in excess of 60% [25]. Adequate exploration of the omental bursa is an advanced technique requiring assessment of coeliac nodes, caudate lobe, supragastric lesser omentum and the recesses on the left lateral aspect. One cannot be certain if these steps had been implemented in the earlier RCTs. Thus leading to inaccurate estimation of residual disease. The potential issue of surgeon bias in estimating residual disease has been highlighted

Indeed three further RCTs are examining the question of primary debulking surgery versus neoadjuvant chemotherapy [27, 28]. In fact all three trials include physiological status of the patient in their inclusion criteria. This feature was lacking in the CHORUS trial; EORTC 55971

The Japanese studies (JCOG0602) and the Italian (SCORPION trial) studies have published the peri-operative outcomes [27, 28]. As expected both of these studies demonstrate fewer perioperative complications, shorter length of stay and smaller blood loss after neoadjuvant che-

The Japanese multicentre study recruited 301 between 2006 and 2011. In total, 8 cycles of carboplatin and paclitaxol were administered. Those patients with a residual tumour of >1 cm following PDS were offered IDS after 4 cycles of adjuvant chemotherapy. This is despite the publication of GOG152 by Rose et al. in 2004 demonstrating no advantage to second look laparotomy after a maximal effort at PDS [22]. Another peculiarity of this study is the interval of more than 4 years between recruitment of the last patient and submission of the manuscript.

The 'optimal debulking' rate in this study, defined as residual tumour of <1 cm, was 82% in the NACT and 37% in PDS group; when all treated patients are taken into account, including the second-look laparotomy, then the optimal debulking rate changes to 71 and 63% in the NACT and PDS arms respectively [28]. The grade 3–4 complications were less frequent after NACT compared to PDS. Resection of 'abdominal organs' and 'distant metastasis' were more common after PDS. Curiously the duration of main surgery was longer in NACT (302 versus 240 min); this may be explained by the significantly higher rates of pelvic and para-aortic lymphadenectomy in the NACT arm (pelvic LND 72.3% versus 27.2%; para-aortic LND

In the phase 3 Italian study, Fagotti and colleagues set out to investigate the best strategy for managing patients with high tumour load [27]. Patients were recruited between 2011 and 2014.

TRUST trial.

in a radiological referencing study [26].

240 Ovarian Cancer - From Pathogenesis to Treatment

49.2% versus 11.6%) [28].

excluded patients with PS 3 or 'serious disabling disease'.

motherapy compared to primary debulking surgery.

strategy.

The two most important prognostic characteristics in ovarian cancer are comprehensive staging and optimal cytoreductive surgery [21]. Disease morphology (as predicted by cross sectional imaging and/or laparoscopic assessment), physiological fitness of the patient and the skill set of the surgeon or surgical team are the three key domain determining the resectability.

Since we have long abandoned the concept of second look laparotomy, it is important that where risk of residual exists, we must seek alternatives to primary debulking surgery, otherwise the patient may be dealt with a treatment strategy which is overall suboptimal. Therefore can biochemical, molecular imaging or endoscopic assessment help predict optimal surgery? This subject is a vast area and it will be briefly reviewed here in the context of cytoreductive surgery for advanced ovarian cancer.

The reader should exercise caution in interpreting results from studies for two key reasons; each study will use a different protocol for the index test of interest and secondly the assessment of residual disease is not without bias [32].

institutional (and national climate), organisation & management, work environment, team, individual staff member, task and patient [45]. How this model could be used for maximising

Surgical Management of Ovarian Cancer http://dx.doi.org/10.5772/intechopen.80891 243

The statement by the CMO above creates a national sense of the overall aim. In addition, the European Society of Gynaecological Oncology (ESGO) published a benchmark regarding ovarian cancer surgery, which adds to this impetus, about the desirable end goal [46]. This expert consensus report recommends 10 indicators relating to structural, process and outcome metrics ranging from individual performance to team decision making process within a

Around the globe and even within the 'developed' nations the practice of patient selection, planning and delivery of upfront surgery varies a great deal. Therefore in terms of organisation and management, centralization of care delivery will help optimise outcomes [26, 47]. With regard to team and individual factors, training should target both and the end goal should be clear to both entities, that is, microscopic clearance of the disease. The delivery of surgery could be by a sufficiently trained gynaecological oncologist with the appropriate contribution from allied surgical oncologists. ESGO have organised or sponsored numerous workshops targeting technical skills and the philosophy to support primary debulking surgery. Such a concerted effort will help to redress one of the concerns about current training. The application of the current 'gold standard' evidence from two randomised controlled trials, (though heavily criticised) will adversely impact the training of the next generation of surgeons. Further, the timing of TRUST trial outcome and retirement of those trained prior to the

Indeed individual and team training can be augmented by not only skills training in workshops, but through buddy operating during the transition phase. Such an endeavour could be supported by virtual platforms to maintain skills (e.g. video based feedback on specific sub-

Patient selection is discussed elsewhere in this book and will not be discussed here. The factors will include demographic, biological (including molecular characteristics of the disease) and

Another important measure in improving the outcomes as part of CRS is to enhance chemotherapy with the use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC). In a recent study, addition of HIPEC to CRS appears to prolong the overall survival by almost 12 months in patients undergoing interval debulking surgery [51]. This offers an exciting complement to maximal effort CRS. These findings will require independent verification prior to widespread

At present the grade A evidence reveals no significant difference in the 5 year survival amongst patients receiving either primary or interval debulking surgery for ovarian cancer. It

multidisciplinary setting. Such a suite of benchmarks can set the direction of travel.

wide acceptance of PDS, will change the landscape of practitioners.

adaptation. This topic will not be discussed further in this chapter.

radiomics to mention a few [50].

8. Conclusions

tasks in cytoreductive surgery) [48, 49]. This will augment task performance.

optimal cytoreductive surgery is briefly illustrated here.

Several studies have demonstrated that preoperatively raised level of CA125 and HE4 can predict suboptimal debulking [33–35]. Indeed higher platelet count, lower lymphocyte count or higher ratio of platelet to lymphocyte count can predict suboptimal debulking in advanced ovarian cancer [36, 37].

Functional imaging such as diffusion weighted MRI and PET-CT are rapidly evolving. The key aspect for imaging should be able to identify the rate limiting steps in relation to cytoreductive surgery. Diseases on small bowel mesentry and bowel serosa are consistently the rate limiting steps in delivering microscopic clearance of the disease. At present there is significant interest in diffusion weighted MRI and a prospective imaging study is underway to delineate the role of multiplanar MRI with CT as compared with standard CT alone in guiding decision making process (ISRCTN51246892). In a recent paper, the dwMRI appears to perform very well in predicting disease map [38]. The role of CT on its own in predicting resectability provides does not provide a consistent acceptable answer particularly as the current standard of 'optimal' debulking is nil visible disease [39–41].

Laparoscopic assessment can be useful adjunct in patient selection. One must acknowledge that a laparoscopic assessment can only provide information regarding the intraperitoneal disease. Fagotti and colleagues have accomplished a body of work regarding the role of laparoscopy in advanced ovarian cancer. Studies have consistently shown that small bowel and its mesentry are common site for the residual disease [27, 31, 42]. Petrillo et al. de on laparoscopic assessment, where unresectability is indicated by a predictive score of greater than 8 [31].

It is likely that a combination of metabolic analysis and morphologic characteristics will enhance non-invasive prediction of resectability in the medium future.
