- Email: [email protected]
Neoadjuvant chemotherapy for ovarian cancer: do we have enough evidence?
Comment
Neoadjuvant chemotherapy for ovarian cancer: do we have enough evidence? radical surgery should focus on proving that primary surgery is more effective than primary chemotherapy with high-quality delayed surgery.4 Hasty conclusions should not be made before we have enough evidence. The second question regarding the surgical outcomes from the CHORUS trial2 is about patient selection. Kehoe and colleagues disagreed that the surgical quality in their trial was substandard, and instead attributed the unsatisfactory surgical outcomes to poor performance status or older age of their study population. Consequently, they concluded that only specific subsets of women with ovarian cancer with poor performance status or a heavy tumour burden might benefit from neoadjuvant chemotherapy before delayed surgery. However, which patients benefit most from this treatment strategy remains unanswered. Concerns are also increasing that neoadjuvant chemotherapy could be used as an excuse for neglecting maximum surgical efforts or improvement of competent surgical skills.4 Irrespective of whether these concerns stem from overanxiety, they should not become reality. Importantly, complete removal of the tumour was the most prognostic factor in both EORTC-NCIC1 and CHORUS.2 Even after neoadjuvant chemotherapy, more than 40% of patients with advanced ovarian cancer had gross upper abdominal metastasis that needed radical upper abdominal surgeries to be completely removed.5
www.thelancet.com Published online May 20, 2015 http://dx.doi.org/10.1016/S0140-6736(14)62259-5
Published Online May 20, 2015 http://dx.doi.org/10.1016/ S0140-6736(14)62259-5 See Online/Articles http://dx.doi.org/10.1016/ S0140-6736(14)62223-6
Jim West/Science Photo Library
Although primary cytoreductive surgery followed by chemotherapy has been the standard treatment for advanced ovarian cancer for many years, neoadjuvant chemotherapy followed by interval debulking surgery has emerged as a new alternative treatment of advanced ovarian cancer after the EORTC-NCIC trial.1 In The Lancet, Sean Kehoe and colleagues2 show the benefits of using neoadjuvant chemotherapy for patients with advanced ovarian cancer. In a comparison of primary surgery versus primary chemotherapy in 552 patients with advanced ovarian cancer, they showed that primary chemotherapy was not only equally effective but also a substantially safer strategy. Serious postoperative adverse events and death after surgery were less common in the primarychemotherapy group, and global quality of life was also improved in this group. These findings correspond not only with the data from the EORTC-NCIC trial1 but also with a Japanese randomised study.3 Accordingly, these data lend support to the theory that neoadjuvant chemotherapy decreases treatment-related morbidity in patients with advanced ovarian cancer. Should neoadjuvant chemotherapy before delayed surgery therefore be promoted as a new standard treatment for advanced ovarian cancer? The answer is not straightforward. Unfortunately, the CHORUS trial has a similar weakness to the EORTC-NCIC trial—the low quality of surgical care. For example, in the primarysurgery group in CHORUS,2 27% of patients did not receive bilateral oophorectomy and 24% of patients did not receive a hysterectomy. Additionally, more than 80% of patients did not receive upper abdominal surgeries. As a result, the median time for surgery was only 120 min and optimum cytoreduction was achieved only in 41% of the primary-surgery group. These disappointing surgical outcomes raise two questions. First, whether the findings of the CHORUS trial are applicable to expert surgeons is unclear. Therefore, opponents of neoadjuvant chemotherapy might claim that the results are valid only for less experienced surgeons; however, no evidence is available yet to assume that primary surgery is superior to neoadjuvant chemotherapy only if high-quality surgical care is provided. Hence, future research by advocates of
1
Comment
Neoadjuvant chemotherapy is not, and should not be, the opposite of high-quality surgical care. Despite these questions and concerns, Kehoe and colleagues2 are to be congratulated on their research showing that neoadjuvant chemotherapy lowers treatment-related morbidity without sacrificing treatment efficacy. However, efforts should now be directed towards identifying and resolving the remaining uncertainties.
I declare no competing interests.
Sokbom Kang
5
National Cancer Center, Goyang, 411-769, South Korea [email protected]
2
1 2
3
4
Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010; 363: 943–53. Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 2015; published online May 20. http://dx.doi.org/10.1016/S01406736(14)62223-6. Onda T, Yoshikawa H, Shibata T, et al. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in phase III randomized trial: JCOG0602. J Clin Oncol 2014; 32 (15 suppl): abstr 5508. Chi DS, Bristow RE, Armstrong DK, Karlan BY. Is the easier way ever the better way? J Clin Oncol 2011; 29: 4073–75. Kang S, Jong YH, Hwang JH, et al. Is neo-adjuvant chemotherapy a “waiver” of extensive upper abdominal surgery in advanced epithelial ovarian cancer? Ann Surg Oncol 2011; 18: 3824–27.
www.thelancet.com Published online May 20, 2015 http://dx.doi.org/10.1016/S0140-6736(14)62259-5
Neoadjuvant chemotherapy for ovarian cancer: do we have enough evidence? radical surgery should focus on proving that primary surgery is more effective than primary chemotherapy with high-quality delayed surgery.4 Hasty conclusions should not be made before we have enough evidence. The second question regarding the surgical outcomes from the CHORUS trial2 is about patient selection. Kehoe and colleagues disagreed that the surgical quality in their trial was substandard, and instead attributed the unsatisfactory surgical outcomes to poor performance status or older age of their study population. Consequently, they concluded that only specific subsets of women with ovarian cancer with poor performance status or a heavy tumour burden might benefit from neoadjuvant chemotherapy before delayed surgery. However, which patients benefit most from this treatment strategy remains unanswered. Concerns are also increasing that neoadjuvant chemotherapy could be used as an excuse for neglecting maximum surgical efforts or improvement of competent surgical skills.4 Irrespective of whether these concerns stem from overanxiety, they should not become reality. Importantly, complete removal of the tumour was the most prognostic factor in both EORTC-NCIC1 and CHORUS.2 Even after neoadjuvant chemotherapy, more than 40% of patients with advanced ovarian cancer had gross upper abdominal metastasis that needed radical upper abdominal surgeries to be completely removed.5
www.thelancet.com Published online May 20, 2015 http://dx.doi.org/10.1016/S0140-6736(14)62259-5
Published Online May 20, 2015 http://dx.doi.org/10.1016/ S0140-6736(14)62259-5 See Online/Articles http://dx.doi.org/10.1016/ S0140-6736(14)62223-6
Jim West/Science Photo Library
Although primary cytoreductive surgery followed by chemotherapy has been the standard treatment for advanced ovarian cancer for many years, neoadjuvant chemotherapy followed by interval debulking surgery has emerged as a new alternative treatment of advanced ovarian cancer after the EORTC-NCIC trial.1 In The Lancet, Sean Kehoe and colleagues2 show the benefits of using neoadjuvant chemotherapy for patients with advanced ovarian cancer. In a comparison of primary surgery versus primary chemotherapy in 552 patients with advanced ovarian cancer, they showed that primary chemotherapy was not only equally effective but also a substantially safer strategy. Serious postoperative adverse events and death after surgery were less common in the primarychemotherapy group, and global quality of life was also improved in this group. These findings correspond not only with the data from the EORTC-NCIC trial1 but also with a Japanese randomised study.3 Accordingly, these data lend support to the theory that neoadjuvant chemotherapy decreases treatment-related morbidity in patients with advanced ovarian cancer. Should neoadjuvant chemotherapy before delayed surgery therefore be promoted as a new standard treatment for advanced ovarian cancer? The answer is not straightforward. Unfortunately, the CHORUS trial has a similar weakness to the EORTC-NCIC trial—the low quality of surgical care. For example, in the primarysurgery group in CHORUS,2 27% of patients did not receive bilateral oophorectomy and 24% of patients did not receive a hysterectomy. Additionally, more than 80% of patients did not receive upper abdominal surgeries. As a result, the median time for surgery was only 120 min and optimum cytoreduction was achieved only in 41% of the primary-surgery group. These disappointing surgical outcomes raise two questions. First, whether the findings of the CHORUS trial are applicable to expert surgeons is unclear. Therefore, opponents of neoadjuvant chemotherapy might claim that the results are valid only for less experienced surgeons; however, no evidence is available yet to assume that primary surgery is superior to neoadjuvant chemotherapy only if high-quality surgical care is provided. Hence, future research by advocates of
1
Comment
Neoadjuvant chemotherapy is not, and should not be, the opposite of high-quality surgical care. Despite these questions and concerns, Kehoe and colleagues2 are to be congratulated on their research showing that neoadjuvant chemotherapy lowers treatment-related morbidity without sacrificing treatment efficacy. However, efforts should now be directed towards identifying and resolving the remaining uncertainties.
I declare no competing interests.
Sokbom Kang
5
National Cancer Center, Goyang, 411-769, South Korea [email protected]
2
1 2
3
4
Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010; 363: 943–53. Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 2015; published online May 20. http://dx.doi.org/10.1016/S01406736(14)62223-6. Onda T, Yoshikawa H, Shibata T, et al. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in phase III randomized trial: JCOG0602. J Clin Oncol 2014; 32 (15 suppl): abstr 5508. Chi DS, Bristow RE, Armstrong DK, Karlan BY. Is the easier way ever the better way? J Clin Oncol 2011; 29: 4073–75. Kang S, Jong YH, Hwang JH, et al. Is neo-adjuvant chemotherapy a “waiver” of extensive upper abdominal surgery in advanced epithelial ovarian cancer? Ann Surg Oncol 2011; 18: 3824–27.
www.thelancet.com Published online May 20, 2015 http://dx.doi.org/10.1016/S0140-6736(14)62259-5