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Fear of Cancer Recurrence in Patients With Localized Renal Cell Carcinoma
, PhD1; Dena Battle2; Errol J. Philip , PhD3; Paulo Gustavo Bergerot , MD1; Pavlos Msaouel , MD, PhD4; Allan ‘Ben’ Smith , PhD5; Adeola Esther Bamgboje, PhD5; Brian Shuch, MD6; Ithaar H. Derweesh, MD7; Eric Jonasch, MD4; Adam P. Stern, MD8; Sumanta K. Pal , MD1; and Michael Staehler , MD, PhD9 Show More
Abstract
Patients with cancer commonly report distress and fear of cancer recurrence (FCR) impacting quality of life and clinical outcomes. This study aims to test the association between emotional well-being and clinical characteristics of survivors with localized renal cell carcinoma (RCC).
Survivors with localized RCC were invited to participate in this study through social media by the Kidney Cancer Research Alliance. Participants self-reported clinical characteristics, distress (Distress Thermometer), and FCR (Fear of Cancer Recurrence-7). Ordinal regression was used to test the association between emotional well-being and patient characteristics.
A total of 412 survivors were included in this analysis. Participants were mostly female (79.4%) and well educated (58.3%), with a median age of 54 years (range, 30-80 years) and median time since diagnosis of 17.5 months. More than one half were diagnosed with stage I disease (56.1%). Most patients (62.3%) had a clear understanding of their diagnosis. A high prevalence of moderate to severe distress (67.0%) and FCR (54.9%) was reported across all survivors of RCC. Higher FCR was associated with female gender, younger age, and lack of understanding of their diagnosis (P = .001), whereas more recent diagnosis was associated with higher distress levels (P = .01).
In the United States, it is estimated that 73,820 adults will be diagnosed with kidney cancer, with 90% diagnosed with renal cell carcinoma (RCC).1 RCC is the sixth most common cancer among men and the eighth most common among women, with nearly 70% diagnosed with early-stage disease. Overall, 75% of patients have an encouraging 5-year survival rate, whereas only 12% of those with distant metastasis will be alive at 5 years.1-3 Surgery remains the primary treatment approach. In those who undergo surgery, there are multiple algorithms to predict recurrence. A recent study by Correa et al4 juxtaposed multiple nomograms, suggesting that the Memorial Sloan Kettering Cancer Center nomogram was the best predictor of recurrence-free survival. Using this algorithm, we estimated a risk of recurrence at 5 years of 19% across stage I to III disease; however, recurrence rates varied substantially on the basis of factors that include tumor size, stage, Fuhrman grade, and the presence of necrosis or microvascular invasion.5 Although adjuvant therapy with sunitinib is available, the benefit of this approach (applicable to only pT3-4 patients) is dubious, as studies have shown no extension of overall survival.6
In general, cancer is a common, life-threatening disease that is often associated with psychological distress and functional impairment. For those with early-stage disease, fear of cancer recurrence (FCR), defined as the “fear, worry or concern relating to the possibility that cancer will come back or progress,”9(p3265) is a common source of distress and frequently unmet clinical need.7-9 Efforts have long been under way to better understand this form of distress and to identify effective ways by which to address this common issue.10
As survival rates have increased across many cancers, research in the field of FCR has expanded considerably. A recent international Delphi study showed that FCR is characterized by persistent preoccupation and worry, as well as by hypervigilance and hypersensitivity to bodily symptoms.11 Additional studies have identified risk factors that may contribute to FCR, including younger age, female gender, lower education, physical symptoms, illness severity, treatment type, and length of treatment.12,13 Whereas milder levels of FCR may be adaptive, higher levels are associated with dysfunction and distress and may warrant comprehensive assessment and psychological intervention.14 In certain cases, symptoms of FCR can be similar to those associated with a host of psychiatric disorders,14,15 with subsequently increased rates of emotional distress (eg, depression or anxiety) and impaired quality of life.13 Despite this growing body of literature, a previous systematic review found somewhat inconsistent evidence on the association between anxiety, depression, and FCR, and emphasized the need for additional research.13
The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers.13 A notable dearth of literature exists concerning rates of FCR among patients with RCC, a patient population who frequently manage their diagnosis for years post-treatment. For these patients, FCR may be associated with their unique treatment and prognosis, especially considering the uncertainty that exists in the routine management of RCC.7 The current study sought to establish the prevalence of FCR among survivors diagnosed with localized RCC and its association with clinical characteristics and distress.
This was a prospective survey study in which participants who were diagnosed with RCC were invited to participate through social media (eg, Twitter, Facebook) by a United States–based nonprofit patient advocacy program (Kidney Cancer Research Alliance). The survey was distributed via SurveyMonkey and hosted on the Kidney Cancer Research Alliance Web site, with interested participants consenting electronically. To be eligible, participants needed to be diagnosed with localized or locally advanced RCC (American Joint Committee on Cancer stage I to III). Duplicate responses and surveys answered by caregivers were excluded.
Participants were asked to provide information regarding their age, gender, marital status, education, annual income, and their current country and place (eg, rural or urban) of residence. Participants were also asked about their cancer histology, disease stage and treatment, and the nature of their care facility. They then completed two validated measures of distress and FCR:
Distress Thermometer: An 11-point visual analog scale that ranges between 0 (no distress) and 10 (extreme distress). A cutoff score ≥ 4 has been shown to be associated with moderate-to-severe distress.16
Fear of Cancer Recurrence-7: A 7-item scale that assesses the degree of FCR. Scores ≥ 17 out of 40 indicate moderate FCR. Scores ≥ 27 indicate severe FCR.17 A high level of internal consistency was established in this patient cohort (α = .84).
Data were analyzed using SPSS Statistics 25 (IBM Corp, Armonk, NY). Descriptive analysis was used to characterize the sample, including demographic and clinical characteristics (age, gender, race, education, country, residential area, care facility, and disease stage) and psychological symptoms (distress and FCR). We used a multivariable ordinal regression model to identify predictors of FCR among sociodemographic and clinical variables.
A total of 1,150 participants responded to the survey. Of these, 412 had localized disease and were included in the current analysis. The remainder were either not patients themselves (mostly caregivers) or had stage IV disease. Participant’s characteristics are listed in Table 1. In brief, participants were a median age of 54 years old (range, 30-80 years) and were predominantly female (79.4%) and college educated (58.3%). Survivors resided in suburban (48.1%) or rural (32.0%) areas and were mostly from the United States (85.0%), Canada (3.9%), Germany (2.4%), Australia (2.2%), or the United Kingdom (2.2%). Participants were also predominantly diagnosed with stage I disease (56.1%). Most patients were treated at an academic hospital (37.3%) or regional cancer center (28.1%), with the majority reporting they were approximately 1 hour (68.9%) or 2 hours (18.6%) from their treatment facility. Median time since diagnosis was 17.5 months (range, 2-684 months), and the majority of survivors stated that they had a clear understanding of their diagnosis and felt confident about the treatment prescribed (62.3%).
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The majority of participants (67.0%) reported a moderate-to-severe level of distress, whereas fewer individuals, but still a substantial number, reported moderate (45.9%) or severe (9.0%) FCR. Results of the ordinal regression model indicated that there was a significant association between FCR and several factors, including female gender, younger age (< 65 years), and lack of comprehension regarding their diagnosis (P = .001; Table 2). Of interest, disease stage was not associated with distress or FCR (Appendix Fig A1, online only). Of note, time since diagnosis was negatively associated with distress (P = .01) but not with FCR (P = .09; Fig 1).
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Fig 1. Comparison between emotional well-being and time since diagnosis (quartile distribution). (A) Distress. (B) Fear of cancer recurrence.
To our knowledge, this is the first study to examine FCR among survivors diagnosed with localized RCC and its association with sociodemographic and clinical characteristics. Survivors who were diagnosed with localized RCC reported significantly higher rates of FCR and distress, indeed higher than the average prevalence described in the literature (21% to 40% for FCR and 35% for distress; P < .01) among patients diagnosed with other cancers, which suggests that these individuals are a vulnerable population.13,18 The higher prevalence of FCR may be a result of characteristics related to localized RCC and its treatment, potentially exacerbated by the high chance (20% to 40%) of recurrence. This is hypothesis generating and highlights the relevance of ensuring an accurate understanding of diagnosis and prognosis. Furthermore, FCR often presents as intrusive, with negative thoughts about cancer and a consistent focus on unrelated symptoms, which may lead to either an overuse of health care resources or poorer adherence to follow-up recommendations, as well as impairments in social and physical functioning.10,19
Of note, whereas distress was lower in patients further from diagnosis, FCR did not seem to dissipate to the same degree (Fig 1), as observed in other populations of survivors of cancer.13 This highlights the relevance of assessing FCR among survivors irrespective of time since diagnosis and providing supportive care to assist patients in coping with their diagnosis. A recent systematic review and meta-analysis demonstrated that evidence-based treatments targeting FCR that were primarily delivered face to face had a robust effect on symptoms.20 Additional evidence is needed regarding the efficacy of more scalable, remotely delivered FCR interventions, with mixed results to date. Furthermore, recent studies have shown promising results for online supportive care programs that address FCR, even without a counselor’s involvement.21,22
Of interest, the prevalence of FCR was not associated with social (race, education level, country, and residential area), practical (cancer care facility type and travel time to hospital), or clinical characteristics (disease stage and time since diagnosis). This is consistent with recent research showing that psychological factors (eg, beliefs about worry) are more closely associated with FCR than demographic or medical characteristics.23 However, we did find that younger age, female gender, and understanding information played a prominent role in predicting FCR, similar to findings in survivors of other cancer types.24-26 Furthermore, there is no consensus about the relationship of prognostic indicators (eg, tumor size and disease stage) and FCR13,27; however, two meta-analyses showed that receiving treatment for localized disease (surgery and adjuvant therapy), including breast, colorectal, gynecologic, testicular, and pancreatic cancers, may increase the risk of FCR.28,29 Curiously, disease stage was not associated with distress or FCR, suggesting that actual prognosis may be disconnected from perceived prognosis. Previous studies have shown that patients tend to harbor an inaccurate expectation of cure, and this may be associated with poor satisfaction with cancer care.30-32
Several limitations should be noted. First, recruitment of patients through social media may have introduced bias, considering the high prevalence of women in this study despite RCC being more common in men than women.33 Second, this is a cross-sectional study and thus longitudinal studies are required to better understand the association between prognostic factors and FCR. Third, the unbalanced proportion of patients in each country limits the conclusions that can be drawn regarding the relationship between nationality and FCR. Finally, it is challenging to confirm the data supplied in this survey (eg, cancer stage) because of the nature of distribution; participants were obtained via social media, and there was no direct access to patient charts. It is for this reason that we opted not to obtain other potentially relevant data. For instance, we did not query patients regarding the presence or absence of depression or anxiety disorders, because we would not be able to confirm whether this was a true Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, diagnosis.
In summary, our findings suggest that survivors who are diagnosed with localized RCC are at considerable risk of FCR. Furthermore, we demonstrate that some characteristics—younger age, female gender, and poorer understanding of their disease—may place certain individuals at increased risk of FCR. However, the majority of patient characteristics—type of cancer center, country and place of residence, and disease stage—were unrelated to FCR. Critically, whereas rates of distress lessened as patients moved further from treatment, FCR did not seem to dissipate over time. Thus, targeted interventions to address FCR (eg, educational strategies or psychotherapeutic approaches) in survivors of RCC should be studied.
Presented at the 2020 ASCO Genitourinary Cancers Symposium, San Francisco, CA, February 13-15, 2020.
S.K.P. and M.S. contributed equally to this work.
Conflicts of Interest Statement: The authors have declared that no competing interests exist.
Conception and design: Cristiane Decat Bergerot, Dena Battle, Errol J. Philip, Paulo Gustavo Bergerot, Adam P. Stern, Sumanta Pal, Michael Staehler
Collection and assembly of data: Cristiane Decat Bergerot, Dena Battle, Sumanta Pal, Michael Staehler
Data analysis and interpretation: Cristiane Decat Bergerot, Dena Battle, Paulo Gustavo Bergerot, Pavlos Msaouel, Allan ‘Ben’ Smith, Brian Shuch, Eric Jonasch, Sumanta Pal, Michael Staehler
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Honoraria: Exelixis, Novartis, EMD Serono
Consulting or Advisory Role: Pfizer, Exelixis
Travel, Accommodations, Expenses: Exelixis, Novartis, EMD Serono, Pfizer (I)
Other Relationship: Pfizer, EMD Serono, Bristol Myers Squibb, Eisai, Genentech, Exelixis, Merck
Honoraria: Pfizer, Bristol Myers Squibb, Mirati Therapeutics, Exelixis
Consulting or Advisory Role: Mirati Therapeutics, Bristol Myers Squibb
Research Funding: Mirati Therapeutics (Inst), Takeda (Inst), Bristol Myers Squibb (Inst), Gateway for Cancer Research (Inst)
Research Funding: AstraZeneca (Inst), Pfizer (Inst)
Honoraria: Bristol Myers Squibb, Peloton Therapeutics
Consulting or Advisory Role: Bristol Myers Squibb, Pfizer, Peloton Therapeutics
Consulting or Advisory Role: Intuitive Surgical
Research Funding: Pfizer
Consulting or Advisory Role: Pfizer, Novartis, Genentech, Exelixis, Eisai, Ipsen
Research Funding: Exelixis, Pfizer, Novartis, Peloton Therapeutics
Travel, Accommodations, Expenses: Pfizer
Stock and Other Ownership Interests: Calithera Biosciences, Nektar, Merck
Consulting or Advisory Role: Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol Myers Squibb, Astellas Pharma, Ipsen, Eisai
Honoraria: Pfizer, Novartis, Roche, Ipsen, Bristol Myers Squibb, Exelixis, Bayer, EUSA Pharma, Incyte, Astellas Pharma, MSD Oncology, EMD Serono
Consulting or Advisory Role: Pfizer, Novartis, Ipsen, Exelixis, Eisai, Bristol Myers Squibb, EUSA Pharma, Merck Sharp & Dohme, EMD Serono
Speakers' Bureau: Pfizer, Novartis, Bristol Myers Squibb, Eisai, Ipsen, EUSA Pharma
Research Funding: Pfizer (Inst), Genentech (Inst), Exelixis (Inst), Novartis, Bayer (Inst), Bristol Myers Squibb (Inst)
Travel, Accommodations, Expenses: Pfizer, Novartis, Bristol Myers Squibb, Eisai, Ipsen, EUSA Pharma, MSD Oncology, EMD Serono
No other potential conflicts of interest were reported.
ACKNOWLEDGMENT
The authors thank all patients and their caregivers for their significant contributions in sharing their own experience over the cancer journey.
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