Elderly ovarian cancer patients often undergo less radical surgery than their younger counterparts, even with equivalent comorbidities [29]. While maximum debulking surgery remains, during the platinum era, one of the most powerful determinants of survival in advanced ovarian cancer [30], the rate of complete surgery decreases with age [31]. In addition to age itself, reduced debulking contributes to the poorer outcome in elderly patients [31].

Nevertheless, according to many published series, age itself should not interfere with optimal surgical management. For some authors, in optimal surgical conditions, maximal debulking rates are not decreased with age [29, 32–34]. In a retrospective cohort published by Bruchim et al. comparing management of 46 patients 70 years or older to 143 younger patients, only 54.3 % of elderly patients had primary debulking surgical interventions compared to 84.5 % of the younger group (p = 0.001), but age was not a limiting factor for optimal debulking in patients who underwent surgery (53 % vs. 54 % in old versus young groups) [33]. The same conclusions were drawn by Uyar et al. in a multi-institutional review of ovarian cancer management (131 elderly patients ≥70 years) and Wright et al. in a retrospective series (129 younger patients <70 and 46 ≥ 70) [29, 32]. In both studies, age had no impact on postoperative complication rates, and Wright found that younger and older groups had the same duration of hospital stay and survival [32]. For both Bruchim and Uyar studies, age had a significant impact on platinum-based chemotherapy with higher rates of treatment-related toxicities (mainly haematological), dose reductions and treatment delays in the older group [29, 33]. Such non-significant differences between elderly and non-elderly patients’ outcomes after surgery can be explained by significant improvements in surgical techniques and perioperative intensive care during the 1980s that yielded to a decrease in perioperative mortality from 8.9 % to 3.2 % in pre-planned surgical conditions [35].

However, other series suggest a pejorative impact of age on both postoperative outcomes and quality of resection. As suggested by a GOG (Gynecologic Oncology Group) retrospective analysis of six clinical trials, even in standardised surgical procedures and on relatively selected patients, advancing age is associated with larger volumes of residual disease [5]. In a retrospective study on patients older than 80 years, debulking surgery induced a 38 % risk of major postoperative morbidity and 11 % of death or prolonged hospitalisation, but most of them were discharged to home and were able to receive postoperative chemotherapy [36]. Moreover, optimal debulking of less than 1 cm had a major impact on overall survival (32.5 months versus 3.5 months) but was achieved in only 25 % of the patients despite aggressive surgical effort. In another retrospective study (2001–2006) on 85 octogenarians patients, 86 % presented with advanced disease, 80 % had cytoreductive surgery and 74 % were left with <1 cm residual disease. But death prior to hospital discharge and within 60 days of surgery occurred in, respectively, 13 % and 20 % of patients. Among patients who underwent surgery, 13 % were unable to receive planned adjuvant therapy, 22 % were treated with single-agent platinum and 37 % completed less than three cycles of chemotherapy. This led the authors to conclude that patients over 80 years may not tolerate combination surgery and chemotherapy and that the high proportion of postoperative complications and deaths argues for a more prudent approach to management in this group of patients [37]. Similar conclusions can be driven from a population-based cohort performed during the 1990–2000 time period. Short-term outcomes of 168 octogenarians were compared to those of 2249 younger patients. Octogenarian patients were significantly more likely to have a longer hospital stay (median 10 days vs. 7 days, p < 0.0001) and a 2.3-fold higher 30-day mortality rate (5.4 % vs. 2.4 %, p = 0.036) [38].

More globally and according to the SEER cancer statistic reviews, age remains the most predictive factor for suboptimal surgical management. Optimal surgical procedures were performed in 43.7 % of patients <60, 29.5 % between 60 and 79 years and 21.7 % ≥80 years between 1973 and 1999 [3]. Similar rates (21 % and 40 %, respectively) have been observed in two successive phase II trials from the French GINECO group, designed for analysing the feasibility of two chemotherapy regimens, the first from 1998 to 2000 and the second from 2000 to 2003 [39, 40]. Reasons for this suboptimal surgical treatment include fear of more advanced cancers at time of diagnosis, presence of comorbidities and some nonmedical factors such as socio-economic or racial origins [41, 42]. Elderly people also are more often cared for by nononcologists such as general surgeons and obstetricians/gynaecologists [43] or in emergency conditions [38] for cancer complications (occlusion, perforation, infection) and are less likely to undergo surgery at a university hospital [38].

According to 1995–2005 SEER database, among the 5475 women aged 65 and older who had primary debulking surgery for stage III or IV epithelial ovarian cancer, the overall 30-day mortality was 8.2 %, 5.6 % for those admitted electively and 20.1 % for those admitted emergently. Risk factors among patients admitted electively were advancing age, increasing stage and comorbidities. A subgroup of patients at high risk of 30-day mortality (12.7 % [95 % CI 10.7–14.9 %]) was identified and included patients aged 75 or older with either a stage IV disease or a stage III disease and a comorbidity score of 1 or more [44].

Finally, Jorgensen published in 2012 the results of a vast nationwide database evaluating the clinicians’ behaviours when facing ovarian cancer in the elderly in Denmark. During the 2005–2006 time period, patients aged 70 and older were 348 and represented 36.2 % of the whole population of patients. Age ≥ 70 was independently predictive of not receiving surgery (OR 0.2 [95 % CI 0.1–0.5]), not receiving a carboplatin–paclitaxel standard treatment (OR 0.03 [95 % CI 0.01–0.1]) and poorer PFS and OS. However, this unfavourable impact of age on outcomes ceased after 16 months. In addition, comorbidity was also independently predictive of both not receiving surgery (OR 0.2 [95 % CI 0.1–0.5]) and not receiving standard chemotherapy (OR 0.03 [95 % CI 0.01–0.1]).

These controversial results after surgery and the surgeons’ frequent reluctance to undertake maximal cytoreductive surgery in vulnerable elderly patients led some teams to consider other management strategies, including secondary surgery (see Chap. 6).

In the context of high perioperative morbidity and mortality risks, another challenging question is the place of preoperative assessment. The elderly population should not be considered as a uniform but as a highly heterogeneous population, in which medical and functional assessments play a central role.

In the large field of surgical management of elderly patients, because of higher risks of postoperative morbi-mortality and longer hospital stays, some authors have considered the need for specific preoperative geriatric assessment tools. Some retrospective analyses have identified some covariates of interest, and low serum albumin levels before surgery are significantly associated with suboptimal cytoreduction in univariate and with death in multivariate analyses, along with increasing age [45]. Comorbidities also impact on perioperative morbidity and mortality, as well as the specialty of the surgeon who undertakes the surgery [38].

Since usually used preoperative assessments are not validated in geriatric cancer populations [46], Audisio et al. developed PACE (Preoperative Assessment of Cancer in the Elderly), a specific screening assessment [47] combining indices from geriatric and anaesthesia fields (a screening tool called CGA for “Comprehensive Geriatric Assessment”, the BFI or Brief Fatigue Index and ASA and Satariano indices). Its validation included 389 older patients, although inclusion was restricted to patients having a MMS score ≥ 18 for ethical reasons, rendering it difficult to extend to mild to moderate cognition deficits. Some components of this mixed screening tool were predictive of 30-day morbidity and mortality and length of hospital postoperative stay – IADL (instrumental activities of daily living) score < 8, PS (performance status) > 1 and moderate to severe fatigue (BFI) score (>3) – yielding the authors to conclude that this screening tool should be used for future studies.

More recently, two articles explored the correlation between frailty screening tools and gynaecological cancer surgery outcomes in the elderly. Frailty is considered as a major topic in geriatrics, defined consensually as “a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes”, but a matter of debate considering its outlines. A first theory interprets frailty as a multidomain phenotype due to the accumulation of deficits and/or comorbidities. This view favours an extensive comprehensive geriatric assessment and was evaluated using the modified Frailty Index (mFI) developed by George et al. The mFI correlates with morbi-mortality after a gynaecological cancer surgery [48]. A second theory – called the phenotypic theory – interprets frailty as a special entity, closely linked to sarcopenia and denutrition [49]. According to this theory, some functional markers as the gait speed, fatigue and weight loss are more significant markers. Such a view was favoured by Cesari et al., who demonstrated that Short Physical Performance Battery (SPPB), usual gait speed (UGS) and instrumental activities of daily living (IADL) score are the best predictors of elderly patients operated for gynaecological cancers [50].

In their 2012 session, Nice/Saint Paul de Vence practical guidelines on ovarian cancer have proposed the following recommendations:

As with surgical management, some differences appear in the literature between dogma and real practice. During the first randomised trials of the platinum era, elderly people were either excluded or selected on restrictive inclusion criteria. Nevertheless, some subgroup analyses were published, concluding that the chemotherapy protocols have similar risk benefit ratios [57], with perhaps slightly increased hematotoxicity but decreased gastrointestinal secondary events, better quality of life during chemotherapy [58] and the same efficacy [59, 60]. In a subgroup analysis of the AGO-OVAR3 trial which recruited 103 patients over 70 years (median age: 73), there was no difference between elderly and younger patients in terms of paclitaxel, carboplatin or cisplatin dose intensity as well as chemotherapy tolerance and patient’s quality of life. Febrile neutropenia was more common in older subjects (5 % vs. 1 %, p = 0.005), and treatment was more often prematurely stopped [61]. Despite these increased limiting toxicities, in Eisenhaurer’s analysis of 108 patients older than 65 years, compared to 184 younger ones, treated between 1998 and 2004 at the Memorial Sloan Kettering Cancer Centre, elderly patients demonstrated similar rates of initial response, platinum resistance, PFS and OS to younger patients [60]. Hershman et al. also concluded, from a population-based analysis of the SEER programme database, that even if only half of the patients over age 65 years were treated with platinum-based therapy, survival should improve by 38 % in this group, with similar benefit rates as described among younger patients, justifying an increasing effort to treat elderly patients in a similar way to younger ones [59].

Some controversies appeared from series of older and frailer patients. In Uyar’s analysis of treatment patterns by decades in elderly patients at a multi-institutional level, 36 % of patients of 70–79 years and 41 % of patients over 80 treated with platinum-based chemotherapy required dose reductions or termination of therapy [29]. In Bruchim’s retrospective cohort comparing cancer management of 46 patients over age 70 years to 143 younger ones, elderly patients had significantly more haematological toxicities (75 % vs. 36.3 %; p = 0.001) and were more likely to have dose reductions and treatment delays (60 % vs. 22.4 %; p < 0.001, and 46.6 % vs. 19.1 %; p = 0.004, respectively) [33]. In Ceccaroni’s retrospective analysis of 148 patients over 70 years treated between 1990 and 2000 (median age: 73) in Italian cancer centres, treatment delays over 7 days were often required (16.9 % of the cases) [62]. Villella drew the same conclusion while comparing treatment delays of 31 patients over 70 years to 44 under 55 treated between 1996 and 2001 at the Columbia University College of Physicians and Surgeons [63].

In 2008, Pignata et al. reported the MITO-5 (Multicentre Italian Trial in Ovarian cancer) study, a phase II trial of 26 stage IC–IV ovarian cancer patients. It assessed the tolerance of a weekly carboplatin + paclitaxel schedule: carboplatin AUC 2 + paclitaxel 60 mg/m² d1, d8, and d15 every 4 weeks. They included elderly patients, with a median age of 77, a significant proportion of them having some ADL and/or IADL dependencies, although most were PS 0 or 1 [64]. Only three limiting toxicities were observed (heart rhythm, prolonged haematological toxicity, liver transaminase increase), and four individuals developed grade 1 peripheral neuropathy. Thus this weekly schedule appears currently to be an alternative to the usual carboplatin–paclitaxel standard regimen.

More recently, Pignata published a strictly weekly regimen of carboplatin AUC 2 and paclitaxel 60 mg/m² during 18 weeks, in a nonspecifically geriatric population [65]. Despite the absence of demonstrated benefit of the weekly arm, and perhaps an opposite trend in the older population (151 pts over 70), this regimen was considered in the last NCCN guidelines as an option in the elderly and/or patients with comorbid conditions [23].

Considering the treatment of platinum-sensitive, cancer relapse, CALYPSO randomised clinical trial which compared a carboplatin + pegylated liposomal doxorubicin to a carboplatin + paclitaxel standard in platinum-sensitive relapse. In a subgroup analysis of patients older than 70 (median age: 73) who represented 16 % of the whole populations of patients, an excess in grade 2 and over neuropathies was demonstrated in the carboplatin–paclitaxel treatment arm [66].

To summarise, the real geriatric population is frequently excluded from large prospective studies due to either selective inclusion criteria or investigators’ reluctance to include elderly people in clinical trials. Chronological age, rather than distinct geriatric syndromes which may be reversible, seems the main selection factor. While standard adjuvant chemotherapy with six cycles of carboplatin–paclitaxel [67, 68], is well described, real practice is different. Population-based studies, mainly from the SEER programme, showed a higher rate of monotherapies or even abstention from therapy in elderly people. According to the analysis of Sundarajan et al., using 1992–1996 SEER programme data, abstention reached 17 % of patients over 65 years. Compared to the 65–69 age group, the odds ratio by age group for receiving therapy within 4 months of diagnosis was 0.96 for patients 70–74 years, 0.65 for patients 75–79 years, 0.24 for patients 80–84 years and 0.12 for patients over 85 years of age, showing a dramatic decrease of chemotherapy after 80 years. Reasons for suboptimal treatment include age itself [69], fear of comorbidities but also some nonmedical factors such as socio-economic or racial origin [70]. As previously explained, extensive surgical management itself seems to compromise chemotherapy feasibility in vulnerable elderly people [29, 33], yielding some authors to consider either delayed surgical treatment or even surgical abstention [37].