Differences in Mental Health Outcomes According to the Treatment Received for Men Being Treated with Localized Prostate Cancer Journal Club - Christopher Wallis & Zachary Klaassen
January 5, 2023
Christopher J.D. Wallis, MD, Ph.D., Assistant Professor in the Division of Urology at the University of Toronto.
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Georgia Cancer Center
Association Between Treatment for Localized Prostate Cancer and Mental Health Outcomes.
APCCC 2022: Importance of Lifestyle and Prevention of Complications in Advanced Prostate Cancer: How to Take Care of Brain and Mood?
Mental Health and Impact on Patients with GU Malignancies - Zachary Klaassen
Christopher Wallis: Hello, and thank you for joining us for this UroToday Journal Club discussion. Today we're talking about a recent publication entitled Association between Treatment for Localized Prostate Cancer and Mental Health Outcomes. I'm Chris Wallis, Assistant Professor in the division of urology at the University of Toronto. With me today is Zach Klaassen, Assistant Professor in the division of urology at the Medical College of Georgia.
This is the citation for the recent publication in the Journal of Urology led by Dr. Luckenbaugh and colleagues from the CEASAR group.
As most UroToday viewers will know, localized prostate cancer is a relatively heterogeneous space, and as a result we have guideline-recommended treatment options that include active surveillance, surgery, and radiotherapy that may be most appropriate for differing patients under different clinical circumstances. However, when used in a guideline-concordant way, differences in survival outcomes between these treatment approaches are relatively small. We know, however, that differences in toxicity and adverse events are pretty substantial between these treatment models, and thus far, most studies in prostate cancer have focused on patient-reported functional outcomes, including urinary incontinence and impotence.
However, we know that the effects of both prostate cancer diagnosis and treatment may affect other domains of a man's life and that of his family as well. One of the potentially more poorly studied aspects of prostate cancer outcomes is that of mental health. While the studies are limited, depression symptoms appear to be relatively common in patients newly diagnosed with prostate cancer, and there may be an influence of treatment modality on this. However, available data thus far are limited by small sample sizes and a cross-sectional methodology. However, when examined in breast and colorectal cancers, we do see pretty significant effects of both cancer diagnosis, as well as the effects of potentially disfiguring treatments on mental health outcomes, and so this really warrants further exploration in the context of prostate cancer.
These authors used a prospective population-based cohort study known as CEASAR, which utilizes five population based SEER registries and the CaPSURE prostate cancer registry to identify patients with localized prostate cancer. In this study, they identified patients treated during the year 2011 who met the following criteria: age less than 80, clinical T1 or T2 disease, PSA less than 50, and who are enrolled to start providing information within six months of their diagnosis. These patients then completed surveys at baseline, six months, 12 months, three years, and five years after enrollment, to provide a longitudinal assessment of their symptoms and outcomes.
In this study, the main outcome of interest was depressive symptoms, measured using a modified version of the 10-question validated CES-D10. Domain scores in this ranged from zero to 27, with the highest scores indicating more severe depressive symptoms. They also further assessed emotional well-being as well as energy and fatigue using the SF-36.
The primary exposure of interest was treatment modality, categorized as active surveillance, surgery, or radiotherapy. Radiotherapy may be given either with or without androgen deprivation, based on clinical indication and the treating physician's preference. These exposures were determined by a hand chart review at one year.
The authors examined these outcomes using adjusted means score differences from baseline. They used multivariable longitudinal linear regression models, adjusting for all the covariants listed here which may importantly impact mental health outcomes, including the time since treatment, age of diagnosis, race, education, comorbidity, income, insurance status, D'Amico risk group, registry site, baseline physical function, baseline general health, baseline social support, baseline participatory decision-making, baseline and time-varying sexual function, and a corresponding baseline value for each outcome as it's background assessed. Active surveillance was used as a referent, and the authors compared results between treatment groups. Time trends over time were graphically represented.
I'm going to hand it over to Zach now to walk us through the results of this analysis.
Zachary Klaassen: Thanks so much, Chris. Great introduction. This is the flow chart demonstrating inclusion criteria for this study. As you can see here, there was 3,277 patients that met all the CEASAR inclusion criteria, with an eligibility cohort of 2,954, and an analytical cohort of 2,742, which included 1,419 patients undergoing surgery, 321 undergoing radiation with hormone therapy, 630 undergoing radiation without hormone therapy, and 372 undergoing active surveillance.
This is the table one baseline demographic, socioeconomic, and disease characteristics by treatment type. As you can see here, this is the breakdown by the aforementioned for treatments that we discussed. Several points to highlight from this table, and most of this is pretty intuitive, but I'll just highlight some key points.
As you'd expect, patients undergoing surgery were slightly younger than the other groups at 62 years of age. There was a pretty standard breakdown for racial treatment indications here. As you can see, there was 80% of patients undergoing active surveillance that were white, 76 that underwent surgery, 76%, slightly less, undergoing radiation plus ADT, 69%, and 76% undergoing radiation without ADT. In terms of black patients, slightly more patients undergoing radiation with ADT.
We jump down here to marital status. This has been studied pretty extensively. We can see here that patients that were married were more likely to have active surveillance or undergo surgery at 81% and 84% respectively. And if we jump down here to medium PSA at diagnosis, pretty similar between the two groups, slightly lower for active surveillance and surgery. Radiation with hormone therapy, PSA of seven was the highest PSA for [inaudible 00:06:33] treatment.
In terms of Gleason score, as you'd expect, active surveillance patients, 89% were Gleason six or less. If we move to surgery, pretty even split between 51% of Gleason six, 31% Gleason three plus four, and 10% Gleason four plus three. As you'd expect, patients receiving ADT with their radiation had higher Gleason disease than those without ADT undergoing radiation.
The last point to sort of highlight here is the median depression CES-D 10 score, which was roughly three to four between these groups. And this is a low score, so these patients were coming into this study with low depressive symptoms.
This table looks at the effect of treatment modality on longitudinal assessment of these outcomes, including CES-D 10, the SF-36 emotional well-being, and the SF-36 energy and fatigue. So if you look at these columns, basically this is all of the treatment modalities with active surveillance to control groups of surgery versus active surveillance on the left. Radiation plus ADT versus active surveillance in the middle column. And radiation without ADT versus active surveillance on the right. The take-home message from this is that, over time, as you can see here on the Y axis, there's very little difference between these interventions versus active surveillance with regard to these three outcomes of CES-D 10, emotional well-being, and energy and fatigue.
This is the adjusted models for the exact same outcomes. Again, surgery versus active surveillance on the left, radiation plus ADT versus active surveillance in the middle, and radiation without ADT versus active surveillance on the right. And again, you can see based on the odds ratios on the non-significant P value that there was no difference over time between these interventions, and this is active surveillance, with regards to CES-D. So depression stayed the same over time, regardless of treatment modality.
This is sort of a summary of the multivariable analysis predicting declines in CES-D, so is predicting depression over time. And as you'd expect, older age, higher comorbidity, poor overall health, poor physical function, being unmarried, lower income, and lower baseline participatory decision-making score was associated with depression in this study.
This figure looks at the trend in unadjusted CES-D score by treatment modality over time. You can see surgery in purple, radiation with ADT in green, and radiation without ADT in blue, and active surveillance in orange. Essentially, as you can see here, excellent score is zero. These patients had very stable scores over time regardless of treatment modality. Again, this is the SF-36 emotional wellbeing score. Same color scheme as the previous figure. Excellent scores at the beginning, and continuing through over five years of followup.
In this last figure, this is the SF-36 energy fatigue score by treatment modality. As you can see here, the green, radiation with ADT, we see a slight dip in the energy fatigue score, which then sort of recalibrates itself as we get into three years of followup. As you would expect, this would be, probably, affected by the ADT along with the radiation therapy.
Several discussion points from this study. In this population-based, prospective cohort study of men with localized prostate cancer in the CEASAR cohort, there was no meaningful association between treatment approach and measures of mental health. Previous work out of Canada has demonstrated an increased utilization of antidepressants following prostate cancer diagnosis for patients who receive surgery or radiotherapy, but not those that had active surveillance. Important to note here that this work relied on administrative records and prescriptions as a proxy for symptoms. Importantly, urologists need to seize available opportunities to identify and intervene in patients with mental health concerns, both at the time of diagnosis and during followup.
Several important limitations from this study. The first is that in this observational study, treatment choice is non-random, and thus there is the potential for cofounding by indication. Secondly, a modified CES-D 10 was used with participants completing nine questions rather than 10 in order to reduce the respondent burden. Third, in the context of finding no significant differences, there may be consideration for the potential for a type two error. However, with small differences that are unlikely to be clinically meaningful, an increase in sample size is unlikely to change the study conclusions. And finally, as mentioned in the results, the referent group was those undergoing active surveillance, and perhaps a more appropriate reference group would be healthy matched men without prostate cancer.
So in conclusion, men with localized prostate cancer showed no clinically important differences in mental health outcomes, including depression symptoms, emotional well-being, and energy and fatigue, according to treatment received. Careful evaluation of patients at risk for adverse mental health outcomes is warranted among all treatment groups. And finally and importantly, appropriate psychiatric assistance should be provided to these patients to optimize the comprehensive care we provide the prostate cancer patients.
Thank you very much for your attention, we hope we enjoyed this UroToday Journal Club discussing the CEASAR cohort looking at mental health outcomes among men with localized prostate cancer.