Surgical recommendations in the era of personalized medicine: What can we learn from patient preferences?

Clarifying how to personalize treatment plans to individual patients remains a significant clinical question for the care of patients with cancer. At the time of diagnosis, amidst the emotional anxiety associated with a new cancer diagnosis, patients face several decisions that often include a determination for or against surgery in the development of an initial treatment plan. Not only do these decisions have implications regarding their overall prognosis and chance of cure, they also impact shortand long-term morbidity, which may have lifelong implications to their quality of life. Epithelial ovarian cancer classically presents at a late stage due to the silent nature of the disease, making it the deadliest of all gynecologic cancers. Current clinical practice guidelines for determining surgical care in this population leave the decision for or against initial surgical management to the discretion of the primary physician and the patient without a concrete algorithm. Primary cytoreductive surgery is recommended for fit patients in whom optimal cytoreduction is deemed feasible with a good chance of resection by the surgeon. For those patients who do not fit this criterion for either reason, neoadjuvant chemotherapy (NACT) can be offered without a reduction in survival and with less morbidity. Thorough up-front surgical cytoreduction has been the foundation of treatment of advanced epithelial ovarian cancer in the modern era. Aggressive removal of visible tumor in order to maximize survival was recommended as early as the 1930s, when the benefit was first described by Charles Meigs. Improvements in surgical safety in the 1970s and 1980s allowed radical surgery for ovarian cancer to become standard. However, aggressive surgical intervention is associated with an increase in perioperative complications. In recent decades, an interest of reducing the perioperative morbidity associated with primary cytoreduction has led to a questioning of this traditional surgical dogma of up-front maximum surgical cytoreduction. Several prospective trials have examined the utility of NACT in advanced ovarian cancer, all of which have demonstrated decreased morbidity without an apparent compromise in survival. Several of the earlier trials evaluating NACT were criticized for short debulking time, lower than expected survival time, and lower rates of optimal cytoreduction. More recent trials have addressed many of these concerns but have found similar overall survival with higher morbidity in their primary cytoreduction arms. A recently updated analysis of the JCOG0602 trial, however, did not demonstrate noninferior survival, suggesting that primary cytoreductive surgery may offer a survival advantage to certain patients. The interplay between patient characteristics, tumor biology, and surgical effort and timing in this disease is, however, remarkably complex. Clinical factors such as poor performance status, low albumin level, older age, and more advanced disease may be important determinants of which patients will benefit from NACT. Despite a large increase in the application of NACT in the United States since 2010, most patients still receive primary surgical cytoreduction, and there is a strong rationale to support this practice. Improved outcomes for patients treated with primary cytoreductive surgery were demonstrated in a recent analysis of the National Cancer Database. This statistical significance disappeared when normalized for performance status, suggesting with real-world data that performance status and comorbidities may confound the survival rates seen in NACT studies. Tumor biology of patients with higher preoperative disease burdens is likely different from that of patients with less disease, which may overwhelm the advantage of optimal, aggressive cytoreduction in this select group of patients, but not others. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV disease were grouped in prospective trials, but 2 large observational studies suggest that women with FIGO stage III disease may benefit from primary surgical cytoreduction, while those