Metastatic spine disease—the impact of gender on clinical outcomes and health-related quality of life

Cancer patient

It is a concerning but relatively well-documented fact that women tend to suffer poorer clinical outcomes than men in medical treatment. However, the precise impact of health-related quality of life (HRQoL) and clinical outcomes post-surgery is less well understood. A recent study of metastatic spine disease patients highlighted a paradox: women experienced fewer benefits of treatment in terms of quality of life, but generally lived for longer and had fewer complications than their male counterparts. What does this tell us about the role of gender in patient prognosis, and crucially, what are the implications for surgical practice?

Gender bias is pervasive in many elements of modern life, and medicine is by no means immune. One of the most impactful demonstrations of this was the (US) Institute of Medicine’s Unequal Treatment Report, which saw one male actor and one female actor walk into emergency rooms with identical heart attack symptoms. The two patients received very different treatments despite having the same medical history and clinical presentation—unconscious bias in action. 

For female patients, unconscious bias can be traced right back to the diagnosis of hysteria when women approached doctors with descriptions of their ailments. Their accounts were often dismissed as hyperbole, or at least not clinically accurate, and not sufficiently respected to warrant the appropriate treatment. That is one historic example of unconscious bias, but it is an issue women continue to face when they come into contact with the modern healthcare system.

The crux of the problem is one of communication, and its effects can be seen in many studies of gender-related treatment outcomes, and specifically patient ratings of health-related quality of life (HRQoL). The assumption is that women are going to fare worse than men. That is partly because our diagnostic tools have usually been set towards men. However, the existing literature also suggests significant barriers for effective communication between patient and physician, stemming from differences in gender, status, authority, education, and other factors of that nature.

Therefore, when the greater proportion of surgeons are male, a woman is likely to face more of a barrier in communication with her physician. At the back end of that, her HRQoL score post-op may not be as strong as that of a male patient. The two groups in society identified as having the worst communication problems with their physicians are patients of a lower class, and those who are women.

Primary tumor site impacts women’s health-related quality of life outcomes

This is a difficult and complex subject that the AO Spine Knowledge Forum Tumor wanted to better understand. We have so many experts in spine oncology, all dedicated to making sure their patients get the best outcome, so the question is ‘What is the best way to do this?’ Whether it’s a molecular marker, an EGFR inhibitor, radiation dosing, or factors such as race or gender, we don’t want to leave any stone unturned when we think about how we treat disease.

On issues like unconscious bias, our intention was not to cause a big commotion, but to delve deeper. After all, if we don’t find out the differences, we can’t figure out ways to improve. The study Gender and Sex Differences in Health-related Quality of Life and Clinical Outcomes and Survival After Treatment of Metastatic Spine Disease sought to examine the gender concept and ask if it warrants further study. 

The study undertook a review of patient demographic data, overall survival, treatment details, perioperative complications, HRQoL measures and the Spine Oncology Study Group Outcomes Questionnaire, examining the cases of 207 female and 183 male patients with metastatic spine disease, stratified by gender. Factors including age, smoker status and site of primary cancer were significantly different between the two cohorts.

After surgery, both cohorts of patients experienced significantly improved health-related quality of life outcomes, be it EQ5D, pain scores or any of the other markers we normally use. However, the sensitivity analysis we performed removed gender-specific cancers, such as breast cancer, prostate cancer and ovarian cancer, because we wanted to examine the effect of gender in HRQoL, as opposed to sex. Interestingly, whilst all patients showed improvement after surgery, when we did the sensitivity analysis those benefits actually disappeared for females. They did not necessarily experience the physical, emotional or social benefits observed in the male patients.

This prompted some interesting conversations in the study group, because we had removed the cancer specialists that were accustomed to regularly treating women. If I’m a surgeon who commonly treats people with uterine or breast cancer, I’m used to communicating a picture for women in a way that is clear to them. They understand what the expectations are, and their perception of their quality of care is at the standard they would hope. By comparison, when we look only at surgeons who are speaking to both males and females for, say, lung cancer, women are no longer seeing that benefit. Thus, the improvement in HRQoL outcomes reported by women in the overall study cohort is more likely a result of their primary cancer than their gender. It highlights again the communication barriers present between female patients and their physicians.

Discordance of survival rates and quality of life metrics between genders

There was another noteworthy finding of the survey. Whilst females did not experience the same improvements to health-related quality of life as males, they did record lower complication rates and longer survival times. This finding applied across the main cohort and the sensitivity analysis, showing that gender was the defining factor here. 

This was not surprising in itself – studies of other cancers including lung cancer, renal cell carcinoma and colorectal cancer also saw longer survival times for women – but it does highlight a discordance between survival and HRQoL. While progression free survival (PFS) has historically been a key measure of treatment effectiveness for oncology patients, this discordance adds to a growing body of evidence suggesting that this is not the measure that really matters to patients – and particularly women. For those with advanced metastatic diseases, it is HRQoL factors like pain, anxiety, depression and treatment side-effects that are often more meaningful.

Similarities and differences between males and females in study results:

Similarities  Differences 
Baseline characteristics 
  •  Metastatic tumor characteristics
  • Pre-treatment steroid use
  • Previous treatment
  • Baseline functional status
  • Age
  • Smoking status
  • Primary tumor location

HRQoL Metrics (overall cohort) 

  •  Improvement in SOSGOQ2.0, EQ5D, and NRS pain score
  • Females showed improvement in the SF-36v2 MCS and PCS
HRQoL Metrics (sensitivity analysis gender-specific cancers removed) 
  • Significant improvement in SOSGOQ physical, mental, and social subdomains and on SF-36
  • Significant improvement in SOSGOQ physical, mental, and social subdomains and on SF-36 for males only
  • Females with lower complication profile

These findings point to gender being a prognostic factor in survival and clinical outcomes for patients undergoing treatment for spinal metastases.

Of course, there are some methodological limitations to prospective studies of this kind. AO and the Knowledge Forums are to be congratulated for their ability to get like-minded individuals together to study these questions. However, we still have a long way to go in combining all the data, and a larger future study will be needed to confirm if this is pervasive amongst all the patients.

One of the key challenges is that the average survival time of patients with spine metastases is anywhere from four to 18 months, so you lose a lot of patients for long-term follow-up. You also have the possibility of confounders. For instance, in the US we know that there are racial and socioeconomic disparities, as well as insurance status, which can make a big difference. So a large study of gender and other factors is really important.

Identifying and eradicating ‘expectation mismatch’ to deliver improved care

From there, we need to rethink our approach, from the tools we use to counsel patients, to the way we talk to patients, the things we expect of them, and the things they expect of us. We have touched on the communication challenges between two people with different backgrounds, which can result in a patient-provider discordance. This can lead to vastly different treatment expectations.

For instance, imagine a patient whose number one pastime is cutting their grass, and that task is very important to them. If their surgeon does not value that task or understand its importance to their patient, they might fail to warn them that they will be unable to bend, lift or twist for six weeks. Therefore, there was an expectation mismatch in terms of what the surgery could deliver for that patient. The message may be delivered by the surgeon in the same way for everyone, but the patient received it differently.

Asking a patient what they hope to gain from treatment, and what they view as success, can deliver significant benefits in their care. For one patient, their priority might be making it to their sister’s wedding, while another may tell you they just want to be able to get out of bed and not be a burden to their family. Once those expectations are articulated, you can talk through the imaging and clinical findings and discuss the likelihood of those being met. This has the further advantage of securing buy-in to the treatment plan (‘If you want to return to gardening you will need to undergo physiotherapy’, for example) or on the flip side, helping patients to decide if they would actually prefer not to undergo a certain intervention.

Often, the first place to start is at the end. How much does the patient understand about their prognosis and the goals they can accomplish within their timeline? As our study highlights, for many patients at the end of life, treatment success may hinge less on the quantity, and more on the quality, of their time.

About the authors:

Dr Rory Goodwin is the Director for Spinal Oncology and the Surgical Director for the Duke Center of Pain and Spine Metastases in North Caroline. He's also an Assistant Professor at the Duke University Medical Center. Dr. Rory is a graduate of Johns Hopkins University School of Medicine, where he has obtained his MD and PhD in neuroscience and where he has also completed the neurosurgery residency program at Johns Hopkins Hospital. Dr. Rory has a research interest in transitional biomarkers and clinical outcomes for patients diagnosed with spinal tumors and genomic and proteomic predictors in brain and spinal oncology.
Andrea Goodwin is a PhD candidate in sociology at the University of North Carolina at Chapel Hill. Prior to beginning her doctoral studies, she earned a Master of Arts in Sociology at Morgan State University in 2011, as well as a Bachelors Degree of Science and Master of Science in Exercise and Sports Sciences from the University of Florida in 2001 and 2003 respectively. Andy works to identify the situation between race, ethnicity, socioeconomic status, and gender and caregiving in the US context.

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