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Despite the fact that most patients with ovarian cancer have stage III or IV disease, advances in surgical and medical therapies over the last 4 decades have significantly improved the 5-year and overall survival (OS) for women diagnosed with ovarian cancer.1,2 What used to be a death sentence can now be considered a chronic disease in many cases.3 However, ovarian cancer is still the leading gynecologic malignancy cause of cancer-related deaths in high-income countries.4 Furthermore, there is much work to be done in efforts to improve not only OS and progression-free survival (PFS), but also QOL. According to the National Comprehensive Cancer Network, the current primary treatment of advanced epithelial ovarian cancer is optimal cytoreductive surgery followed by six to eight cycles of dual-agent platinum- and taxane-based chemotherapy.5 Cytoreductive surgery (also called “debulking”) was initially proposed by Meigs in 1934.6 Forty years later, Griffiths showed that survival depended on the maximum diameter of residual disease left after cytoreductive surgery.7 Primary debulking surgery has since been repeatedly demonstrated as one of the key factors in improving survival and the cornerstone of ovarian cancer treatment by many studies.8-10 There are some in the field of gynecologic oncology, however, who propose that inherent tumor biology is more important than surgical resection and question the value of extensive cytoreductive surgeries as the first step of the advanced ovarian cancer treatment plan. Within the last decade, this issue has been widely debated. In 2008, Vergote presented the data of the first randomized control phase III trial comparing PDS versus NACT followed by interval debulking surgery (IDS). The trial enrolled more than 600 women with bulky stage III or IV advanced ovarian cancer and was conducted by the European Organisation for Research and Treatment of Cancer–Gynecologic Cancer Group (EORTC-GCG) and the National Cancer Institute of Canada (NCIC) Clinical Trials Group. They found no major difference in the PFS and OS between the two treatment arms and concluded that NACT with IDS was not inferior and possibly safer than the current standard of care, PDS.11,12 The recently published trial on primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS) supported the EORTC/NCIC results. In the CHORUS trial, more than 550 women with advanced ovarian cancer were randomly selected to receive primary chemotherapy versus primary surgery, with similar conclusions that NACT/IDS yielded comparable survival results and decreased surgical morbidity when compared with PDS.13 THE ARGUMENT FOR PRIMARY DEBULKING SURGERYIt Is PossibleIt is well accepted that patients who undergo suboptimal tumor cytoreductive surgeries are at risk for surgical morbidity without deriving the survival benefit of the debulking procedure.14,15 However, when a patient is treated with the appropriate surgery by an experienced surgeon or team of surgeons at an experienced hospital, optimal and even complete gross resection (CGR) at the time of PDS is achievable in a vast majority of cases. Reported optimal cytoreduction rates in the literature range from 15% to greater than 85%.10,16 Many experts agree that this variation is not caused by a difference in geography, case presentation, and/or case selection, but is highly dependent on the surgical training, expertise, commitment, and resources of the primary operating surgeon, team, and institution. Moreover, greater than 40% of patients with advanced ovarian cancer have bulky upper abdominal disease that is difficult to resect, which is cited by many gynecologic oncologists as the most common reason for a suboptimal outcome at the time of PDS.17,18 To address, the widespread nature of advanced ovarian cancer at presentation, two strategies have emerged. One strategy, NACT for three or more cycles followed by the cytoreductive procedure, IDS, followed by the completion of up to six to eight total cycles of chemotherapy, has been proposed as a viable method to decrease preoperative disease burden, increase the rates of optimal cytoreduction, and lower postoperative morbidity. The second strategy has been to expand the surgical armamentarium of gynecologic oncology surgeons to include extensive upper abdominal surgical procedures as needed during their PDS. This approach also increases the rate of optimal cytoreduction, without significantly increasing postoperative morbidity. In 2009, Chi et al demonstrated a change in the surgical paradigm at Memorial Sloan Kettering Cancer Center (MSKCC) that incorporated splenectomy, distal pancreatectomy, cholecystectomy, liver wedge resection, dissection of the porta hepatis, and diaphragm resection/peritonectomy when necessary to achieve optimal PDS. This paradigm change led to an improvement in optimal primary cytoreduction from 46% to 80%. The rate of CGR also more than doubled.19 Multiple U.S. and international studies have supported these findings, demonstrating not only the feasibility, but also the safety, of this approach in expert centers, with the morbidity, mortality, and time to start of chemotherapy not being statistically different from that of pelvic limited surgery.20-24 The complexity of the surgery alone is not a predictor of PFS or OS. When cancer in these patients is optimally debulked to less than 1 cm of residual disease, they are afforded the same survival rates as patients who required only standard pelvic surgery.25-27 Because the surgeries can be more complex, preoperative preparation is crucial, sometimes requiring consultation with general surgeons, surgical oncologists, or hepatobiliary surgeons to assist in the event that disease encountered at PDS is difficult or impossible for the gynecologic oncologist to remove. This can sometimes be difficult at medical centers with less experienced practitioners. Recent analyses have shown that optimal cytoreductive surgery rates are higher among more experienced surgeons at higher-volume hospitals, with gynecologic oncologists at expert centers attaining optimal resection rates of greater than 75%.10,28,29 This is in stark contrast to the 41% to 42% optimal cytoreduction rates reported in the PDS arms of the EORTC/NCIC and CHORUS PDS versus NACT/IDS trials (Table 1).12,13 Moreover, the median operating times of 165 and 120 minutes, respectively, in the PDS arms of the two studies seems to be inadequate for a complete surgical evaluation and attempt at achieving optimal or no gross residual disease status.12,13 These findings question whether the PDS attempted in these two trials were what one would see in more experienced, expert centers. Indeed, it is the duty of the operating physician to give the patient the best chance at achieving CGR, even if that means additional training, multispecialty consultation, or referral to another surgeon. It Decreases ChemoresistanceThere are innate benefits to PDS. Large bulky tumors are often necrotic and hypoxic. Their poor blood supply does not often lend itself to maximal intravenous or intraperitoneal chemotherapy delivery. Comparatively, smaller tumors are well perfused and easier to target.30 At the time of diagnosis and the initiation of treatment, both chemotherapy-sensitive and chemotherapy-resistant cells are present in a patient. Primary surgery decreases the tumor burdens of both of these cell lines and decreases the quantity of cells that can spontaneously mutate to drug-resistant phenotypes.31 Thus, surgical debulking aids in overcoming negative tumor biology.32 Approximately 25% of patients have platinum-resistant disease at the time of their first relapse, and almost all patients who have disease recurrence will eventually become chemotherapy-resistant.33 By initiating chemical debulking first with the NACT approach, the tumor cells have more time to build increased resistance. Breaking up the chemotherapy by introducing IDS in the middle of the six to eight cycles of chemotherapy may also have this effect. It Yields Better Survival OutcomesThe median OS of 66 months in stage III ovarian cancer patients who underwent optimal debulking and were treated with intraperitoneal chemotherapy on GOG 172 was stated to be the longest median survival ever reported in a randomized phase III ovarian cancer GOG clinical trial.34 These results serve as a gold standard for quality care, which future studies should try to attain. Although the PFS and OS for the NACT arms of the EORTC/NCIC and CHORUS trials are consistent with those described in other NACT studies, the overall OS rates of 23 to 30 months in all four arms of these studies, and, in fact, in essentially all studies advocating the NACT/IDS approach, are very low (Table 1).12,13,35 In contrast, a retrospective review of an identical sample population of patients treated during the same time period as the EORTC/NCIC trial at MSKCC, demonstrated a median OS rate of 50 months for all patients treated with PDS.36 A recent publication from the same institution reported a median survival of 72 months for all patients who had undergone PDS regardless of residual disease status (including those who had both optimal and suboptimal cytoreduction; Fig. 1).37 FIGURE 1. MSKCC Primary Cytoreduction OS and CGR Rates  Abbreviations: MSKCC, Memorial Sloan Kettering Cancer Center; OS, overall survival; CGR, complete gross resection; mos, months. CGR, complete gross resection; PDS, primary debulking surgery. CHEMOTHERAPY FIRST: QUICKER IMPROVEMENT IN QUALITY OF LIFE?Quality of Life Is an Essential ParameterQOL is an important parameter in the evaluation of therapeutic interventions and is currently the main mechanism to derive patients’ perspective regarding the impact of any medical intervention. Though not an integral part of standard care, QOL measures are regularly used in prospective clinical trials. Increasingly popular is the use of patient-reported outcomes (PROs), in which QOL measures serve as an inherent element in addition to reported adverse sequelae.38 The increasing importance of QOL is accentuated by data demonstrating that it is also a predictive variable for survival.39 Furthermore, a recent cost-efficacy analysis of the GOG 218 trial determining the benefit of the addition of bevacizumab to platinum-based chemotherapy revealed that the incorporation of QOL outcomes made a meaningful contribution to the results, rendering the addition of bevacizumab even less favorable compared with the Markov model, which excluded QOL outcomes.40 Including QOL outcomes in noninferiority studies as a measure of the morbidity and overall impact of an intervention is undoubtedly of major importance. Although both surgery and chemotherapy are essential interventions in treating patients with advanced ovarian cancer, there is a relative paucity of trials addressing the role of surgery. The surgically based, randomized prospective studies encompass the effect of IDS, the role of secondary cytoreductive surgery at the time of recurrence, the value of lymphadenectomy in debulking, and delayed PDS.12,13,30,41-43 The EORTC/NCIC and CHORUS studies are the only two reported prospective randomized trials addressing the use of NACT in ovarian cancer. In both trials, similar QOL assessment tools were used: the EORTC QLQ-C30 questionnaire version 3, which consists of global health status/QOL multifunctional scales and symptom scales combined with a scale regarding financial difficulties; and the ovarian cancer–specific QOL (QLQ-Ov28).44 These are well-validated and reliable questionnaires used frequently in ovarian cancer studies. The assessments were administered before patient randomization at the end of the third and the sixth cycles of chemotherapy and at 6- and 12-month follow-up visits. In both studies, the end of the third cycle of chemotherapy was the presurgical assessment in the NACT arm of the studies. An Evaluation of Quality of Life in EORTC 55971The EORTC 55971 trial included QOL analysis from more than 400 women from the institutions with best compliance for QOL data collection. This provided sufficient numbers to permit clinically meaningful differences to be detected.44 Good compliance was defined as institutions that had at least 50% compliance at baseline and 35% compliance on average during follow-up over all enrolled patients. The QLQ-C30 scales and single-item questions were linearly transformed to a 0 to 100 scale and analyzed according to the procedures recommended by the EORTC QOL group. A higher score on the functional and global/QOL scales indicated better QOL, whereas a higher score on the symptoms scale indicated poorer QOL. At least a 10-point alteration from baseline was necessary to indicate a major change in QOL. The analysis was also repeated with stratification factors at randomization including country, method of tumor biopsy, International Federation of Gynecology and Obstetrics stage, and largest tumor diameter. There were no differences noted in the QOL functioning or symptom scales between the two arms except for fatigue, pain, and dyspnea. These changes were deemed clinically relevant because there was a 10-point change from baseline. The level of fatigue improved in the PDS arm at the third cycle of chemotherapy and persisted to 12 months, whereas in the NACT arm, the same improvement occurred, though was noted only at 6 months (i.e., no changes during treatment, and persisted to 12 months). The pain scale also improved in both arms to subsequent points of measurement. Regarding dyspnea, an improvement was noted at the sixth chemotherapy cycle and at 6 months in the NACT arm, but not the PDS arm. Though these differences were noted, the overall conclusion was that QOL did not differ between the treatment strategies. However, there was an unusual and notable finding. There was a significant survival difference between institutions with good compliance collecting QOL measures versus those who were less compliant: the median OS was 32 months versus 23 months (p = .0006). Additionally, the optimal debulking rates were nearly twice that in selected versus excluded institutions at 40% and 20%, respectively (p = .001). Although there may be other explanations and possible confounding factors, QOL data collection compliance may also be an indicator of an institution’s “excellence.” An Evaluation of Quality of Life in CHORUSThe CHORUS trial measured similar QOL parameters within the same time frame as the EORTC study. CHORUS reported an equivalent survival pattern in each arm, but with lower median survival rates at 22 months for PDS and 23 months for NACT.13 Notably, the median age of women enrolled was older, at age 65, and 19% had a performance status (PS) score of 2 or 3. The older age and poorer PS probably contributed, in part, to the lower median survival patterns. For the purposes of this article, the QOL data were collected from all possible cases and not confined to the centers with better QOL data collection rates. There was sufficient data available from 102 patients in the PDS arm and 117 in the NACT arm. The Global QOL remained unchanged in both arms, with mean scores of 51.5 (95% CI, 45.8–56.2) at baseline to 69.2 (95% CI, 56.1–64.3) at 3 months, and 53.6 (95% CI, 48.6–58.7) to 58.6 (95% CI, 54.5–62.8; p = .58, respectively). Again, accepting a 10-point change in the mean score as being clinically significant, improvements were noted in nausea/vomiting and dyspnea at 3 months compared with baseline in the PDS arm. In the same time frame, diarrhea symptoms improved in the NACT arm. In both arms, pain and appetite scores improved, whereas abdominal/gastric symptoms and peripheral neuropathy worsened. Not surprisingly, chemotherapy-associated side effects worsened in the NACT arm. These were the only parameters with changes; however, they were not significant. However, if the data are graphically demonstrated, as can be seen in Fig. 2, over the 6-month period, the trend is that the NACT arm showed an improving trend compared with the PDS arm. Hence, is NACT a quicker route to a better QOL compared with the primary surgery approach? Both prospective randomized trials seem to indicate that there are no major statistical differences in QOL between PDS and NACT. However, it may be argued that the trends are of more importance than the exact numbers. Combined with other morbidity data, one could favor the neoadjuvant approach in this patient population. BIOLOGIC CONSIDERATIONS REGARDING THE THERAPEUTIC SEQUENCEHistologic and Genomic Factors to Select PatientsOne argument proposed in support of NACT is to reduce tumor bulk and increase the chance of a complete and potentially less morbid surgical resection. This makes biologic sense in chemotherapy-sensitive high-grade serous ovarian cancer (HGSOC), where response rates to first-line platinum-based chemotherapy approach 75%. However, rare subtypes such as low-grade serous ovarian cancer (LGSOC) and mucinous ovarian cancer (mOC) are much less responsive to standard first-line platinum-based therapy (Table 2).45-54 A small study on LGSOC reported an objective response rate of 3.5% to platinum-based NACT, whereas only 20% of patients with advanced mucinous ovarian cancer recruited to a randomized trial showed an objective response to a first-line platinum combination.45,50 Although numbers of patients included in these reports were small, these data raise important questions regarding the value of NACT in rare subtypes of epithelial ovarian cancer. A major concern with NACT is the risk of progression and loss of opportunity for patients who might go from being candidates for a morbid, but feasible, PDS to not being candidates for surgery at all. In this regard, tumor biology should clearly influence the therapeutic sequence and one could propose a histologically driven algorithm for patients with bulky epithelial ovarian cancer. Recent comprehensive genomic studies in HGSOC have started to identify candidate molecular predictors of platinum sensitivity (BRCA1/2 mutations or alterations in other homologous recombination genes) or resistance (CCNE1 amplifications).55-57 Future studies will be crucial to determine whether these genomic markers may influence the therapeutic sequence for patients with advanced HGSOC. TABLE 2. Response to First-Line Platinum-Based Chemotherapy in Rare Subtype of Epithelial Ovarian Cancer  ExpandEvidence for NACT as a Driver of Chemotherapy ResistanceAs previously mentioned, a risk of the neoadjuvant approach is that treating a greater volume of a heterogeneous tumor with NACT may be driving platinum resistance.58 Retrospective studies have shown that NACT was associated with a higher risk of platinum-resistant relapse, even when IDS resulted in complete macroscopic resection.59,60 In the case of platinum-sensitive progression, lower response rates to a platinum combination have been described after NACT, suggesting that NACT may be compromising responsiveness to subsequent therapy.59,61 Although this remains a hypothetical risk, these studies are limited by their retrospective nature and inherent biases that justified the decision to offer NACT in the first place, which likely explain these patients’ poor outcomes. Similarly, studies evaluating whether the number of cycles of NACT influenced outcome have shown worse survival with more than three or four cycles of NACT even when complete macroscopic resection was achieved at IDS.62,63 Again, because of the retrospective nature of these studies, the poor outcome for patients receiving more than four cycles may simply reflect inherent differences in tumor biology and chemotherapy responsiveness rather than a deleterious impact of more cycles of NACT. In fact, a more recent meta-analysis of 21 studies failed to show that the number of NACT cycles affected survival.64 The only available prospective data come from the two randomized controlled trials of PDS versus NACT, and these failed to show a difference in PFS or OS, making it unlikely that NACT is a major driver of platinum resistance.12,24 In vivo evaluation of chemotherapy responsiveness during NACT.As opposed to the adjuvant setting in which patients are treated with no measurable disease, an advantage of NACT is that it could offer the opportunity for an in vivo evaluation of chemotherapy responsiveness. Careful monitoring of tumor response during chemotherapy could identify nonresponders early and justify treatment change in an effort to improve the efficacy of NACT and long-term patient outcomes. Some prospective studies in locally advanced breast cancer have started to suggest a role for response-adapted NACT where the neoadjuvant protocol is modified according to early tumor response. One trial showed an improvement in PFS and OS among patients with locally advanced breast cancer randomly selected to an adaptive NACT strategy with a chemotherapy switch in case of poor response compared with standard NACT.65 Whether adaptive NACT could be beneficial in ovarian cancer has never been investigated and may be limited by the fact that measuring on-treatment response to NACT is difficult in ovarian cancer.66 Neither improvement in CT imaging nor biologic response by CA-125 are reliable for NACT response evaluation.67 Other technologies such as metabolic imaging by fluorodeoxyglucose-PET or circulating cell-free tumor DNA may offer early-response information during NACT for advanced ovarian cancer. However, to date it is unclear how this information would be clinically useful. A small subset of patients (15%) with HGSOC are refractory and progress clinically and biologically during NACT. The only value of identifying these early nonresponders would be if this could inform clinical decision making. Unfortunately, ovarian cancer does not have an effective alternative to standard neoadjuvant carboplatin and paclitaxel. In vivo evaluation of chemotherapy responsiveness at IDS.Complete resection of all macroscopic disease at PDS has been confirmed as a critical prognostic factor32; however, its value after NACT is less clear because visualization of residual disease may be less reliable after chemotherapy.68 Studies have sought to evaluate whether the degree of pathologic response to NACT could provide prognostic information (Table 3).69-76 A number of studies have confirmed the prognostic value of pathologic complete response (pCR) after NACT. Among patients treated with NACT and no residual disease at IDS, Ferron et al showed that pCR with no viable tumor cells in the surgical specimen occurred in 14% of patients and was predictive of PFS, but the degree of histologic response was not.69 A larger study (322 patients) confirmed pCR (defined as no residual tumor cells in the surgical specimen) as predictive of both PFS and OS, whereas a “good” response not amounting to pCR was not prognostic.70 Several groups investigated composite pathologic response scores, incorporating an assessment of viable tumor cells, fibrosis, inflammatory changes, or macrocytic infiltration, and have shown conflicting results using heterogeneous definitions for pathologic response (Table 3).71-75,77 A more recent study suggested that a three-tier histopathologic chemotherapy response score was reproducible and prognostically meaningful for patients with HGSOC treated with NACT, regardless of debulking status.76 Complete or near-complete pathologic response (defined as a chemotherapy response score [CRS] of 3) was associated with significantly improved PFS (18 vs. 12 months, p < .001) and decreased risk of platinum-resistant relapse (odds ratio [OR] 0.08; p < .001) compared with those tumors showing less in vivo chemosensitivity (CRS scores of 1 and 2). Although the authors concluded that the three-tier scoring system may be useful, in fact, outcomes were only different when considering CRS 3 versus CRS 1/2, making it more of a two-tier system. In addition, CRS 3 included near-complete responses defined as residual viable cells, or nodules larger than 2 mm, and did not predict OS. Although the pathologic response score may need refining and will require prospective validation, taken together these data suggest that an evaluation of in vivo response to NACT at the time of IDS could offer useful prognostic information and may inform postoperative management. The identification of a chemotherapy response score to risk-stratify patients would allow for optimization of postoperative management, consideration of maintenance treatment, or participation in clinical trials, with the aim of improving long-term outcome. The question remains whether the degree of pathologic response is prognostic, or whether the only valid surrogate for OS is pCR strictly defined as no residual cancer cells within the entire surgical specimen. Studies in breast cancer have shown that complete response in both primary site and lymph nodes (occurring in 18% of patients with NACT) is required to predict a major improvement in OS,78 the biologic explanation being that pCR is the evidence that other micrometastatic deposits may have also been eradicated by NACT. Interestingly, the correlation between pathologic response and OS was the strongest for triple-negative breast cancer, a highly proliferative subtype that shares genetic homology with HGSOC. The Neoadjuvant Setting as a Tool to Evaluate New RegimensThe neoadjuvant design may be useful to test new therapies in a faster way and with fewer patients than is required for large adjuvant trials. Given the strong correlation between pCR and OS in breast cancer, new drugs are being evaluated in randomized neoadjuvant trials in which the primary endpoint is an improvement in pCR at surgery.79 pCR rates are somewhat lower in ovarian cancer than in other tumor types (6% to 12%), but randomized studies designed to test the benefit of adding a new agent to standard chemotherapy, where the primary objective would be a major improvement in pCR, could provide a useful signal-finding strategy for new drugs. The advantages of this approach are a translational research opportunity to identify predictive biomarkers and obtaining a rapid answer because results are available within a few months of the last patient who was randomly placed. In addition, the neoadjuvant trial design allows the testing of a novel agent in treatment-naive patients, as opposed to metastatic studies, where prior exposure to multiple lines of chemotherapy may distort drug activity. The U.S. Food and Drug Administration has recently issued a statement that they will strongly consider evidence from randomized controlled studies using pCR as an endpoint to allow accelerated approval of novel therapies.80 Although this guidance was designed for trials conducted in breast cancer, using pCR as an endpoint has the potential to help address unmet needs in high-risk populations in a far shorter time frame than would be required via the conventional approach to drug development.79 Translational Research OpportunitiesDespite exquisite sensitivity to first-line platinum-based chemotherapy, HGSOC almost invariably relapses. Yet the mechanisms underpinning primary or acquired chemotherapy resistance are poorly understood (Fig. 3). HGSOC is characterized by extreme genomic instability and intratumoral heterogeneity (ITH).81 Inherent genetic instability and ITH provide the ideal setting for adaptation and treatment escape and have been shown to drive the accelerated acquisition of multidrug resistance.82 Evidence in HGSOC cell lines suggests that relapse is not caused by linear acquisition of genetic alterations, but rather to treatment-induced selection and expansion of intrinsically resistant clones.83 Most genomic studies to date in HGSOC have focused on comprehensive analyses of the primary tumor, but evidence is emerging that a comparison between matched tumor samples from diagnosis and IDS can reveal the mechanisms accounting for the acquisition of resistance in individual patients. For example, an enrichment of ALDH1-positive cells in post-NACT samples has been demonstrated in some patients and shown to correlate with poor survival post-NACT, suggesting that a cancer stem cell subpopulation may account for chemotherapy resistance.84 Studies among patients with germline BRCA mutations treated with NACT have shown that, although initial response rates to platinum are high, a subset shows restoration of BRCA heterozygosity in the post-NACT sample, suggesting a rapid expansion of subclones without somatic LOH for the BRCA wild-type allele during treatment.85 FIGURE 3. The Neoadjuvant Setting: A Translational Research Opportunity  (A) Fifteen percent of HGSOC cases have refractory disease and progress on NACT. Prognosis is poor and studies are needed to characterize the profile of these primary resistant tumors and develop effective alternatives to carboplatin and paclitaxel. However, HGSOC is very chemotherapy-sensitive and most show an initial response to NACT and may progress to IDS. (B) A small subset (5% to 12%) show pCR with no residual tumor cells after NACT. Prognosis is excellent and studies should focus on finding therapies that increase the proportion of patients achieving pCR. (C) Most HGSOC demonstrate initial sensitivity but despite complete debulking will relapse. Identification of molecular alterations selectively enriched in these post-treatment tumors may uncover mechanisms of acquired resistance and identify new therapeutic targets that could eradicate minimal residual disease. Abbreviations: HGSOC, high-grade serous ovarian cancer; NACT, neoadjuvant chemotherapy; IDS, interval debulking surgery; pCR, pathologic complete response. Profiling HGSOC at diagnosis when the bulk of disease is chemotherapy-sensitive and potentially highly heterogeneous may be relatively uninformative. However, identifying chromosomal alterations or somatic mutational events that occur at low frequency at baseline and are selected for during therapy could uncover new therapeutic strategies to overcome platinum resistance. Given the intrinsic chemotherapy sensitivity of the majority of HGSOC, platinum-based chemotherapy will likely always provide an essential component of the treatment strategy; however, profiling the post-NACT tumor may identify actionable targets and provide the rationale for subsequent clinical trials testing novel agents as maintenance therapy in an effort to eradicate the minimal residual disease post-chemotherapy. FUTURE DIRECTIONS AND CONCLUSIONThe discussed considerations truly underscore the need for further research on the most appropriate sequence of care for women with advanced ovarian cancer. Despite years of debate and two randomized controlled trials, the question of whether surgery or chemotherapy should be the primary treatment strategy has yet to be answered. Survival and QOL-related measures are both of paramount importance because they pertain to overall outcomes. Although we seek to answer these questions, excellent clinical judgment is necessary to carefully and aptly select the appropriate patient for each treatment regimen. Furthermore, there is a definitive role for NACT in the laboratory and in clinical research. Much effort must be made to determine novel approaches to the management of this complicated and ever-evolving disease. |
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