Abstract
Introduction
As treatment options for metastatic castration-resistant prostate cancer (mCRPC) expand
and its patient population ages, consideration of frailty is increasingly relevant.
Using a novel frailty index (FI) and two common frailty screening tools, we examined
quality of life (QoL) and physical function (PF) in frail versus non-frail men receiving
treatment for mCRPC.
Materials and Methods
Men aged 65+ starting docetaxel chemotherapy, abiraterone, or enzalutamide for mCRPC
were enrolled in a multicenter prospective cohort study. QoL, fatigue, pain, and mood
were measured with the Functional Assessment of Cancer Therapy-General scale, the
Edmonton Symptom Assessment System tiredness and pain subscales, and the Patient Health
Questionnaire-9. PF was evaluated with grip strength, four-meter gait speed, five
times Sit-to-Stand Test, and instrumental activities of daily living. Frailty was
determined using the Vulnerable Elders Survey (VES-13), the Geriatric 8 (G8), and
an FI constructed from 36 variables spanning laboratory abnormalities, geriatric syndromes,
functional status, social support, as well as emotional, cognitive, and physical deficits.
We categorized patients as non-frail (FI ≤ 0.2, VES < 3, G8 > 14), pre-frail (FI > 0.20,
≤0.35), or frail (FI > 0.35, VES ≥ 3, G8 ≤ 14); assessed correlation between the three
tools; and performed linear mixed-effects regression analyses to examine longitudinal
differences in outcomes (0, 3, 6 months) by frailty status. A sensitivity analysis
with worst-case imputation was conducted to explore attrition.
Results
We enrolled 175 men (mean age 74.9 years) starting docetaxel (n = 71), abiraterone (n = 37), or enzalutamide (n = 67). Our FI demonstrated moderate correlation with the VES-13 (r = 0.607, p < 0.001) and the G8 (r = −0.520, p < 0.001). Baseline FI score was associated with worse QoL (p < 0.001),
fatigue (p < 0.001), pain (p < 0.001), mood (p < 0.001), PF (p < 0.001), and higher
attrition (p < 0.01). Over time, most outcomes remained stable, although pain improved, on average,
regardless of frailty status (p = 0.007), while fatigue (p = 0.045) and mood (p = 0.015) improved in frail patients alone.
Discussion
Among older men receiving care for mCRPC, frailty may be associated with worse baseline
QoL and PF, but over time, frail patients may experience largely similar trends in
QoL and PF as their non-frail counterparts. Further study with larger sample size
and longer follow-up may help elucidate how best to incorporate frailty into treatment
decision-making for mCRPC.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Geriatric OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Cancer statistics, 2020.CA Cancer J Clin. 2020; 70: 7-30https://doi.org/10.3322/caac.21590
- Epidemiology of prostate cancer.World J Oncol. 2019; 10: 63-89https://doi.org/10.14740/wjon1191
- Prostate cancer in the elderly: frequency of advanced disease at presentation and disease-specific mortality.Cancer. 2012; 118: 3062-3070https://doi.org/10.1002/cncr.26392
- Characterising the castration-resistant prostate cancer population: a systematic review.Int J Clin Pract. 2011; 65: 1180-1192https://doi.org/10.1111/j.1742-1241.2011.02799.x
- Guidelines for the management of castrate-resistant prostate cancer.Can Urol Assoc J. 2010; 4: 380-384https://doi.org/10.5489/cuaj.10167
- Who dies from prostate cancer? An analysis of the surveillance, epidemiology and end results database.Clin Oncol (R Coll Radiol). 2019; 31: 630-636https://doi.org/10.1016/j.clon.2019.04.012
- Optimal treatment sequence for metastatic castration-resistant prostate cancer.Eur Urol Focus. 2016; 2: 488-498https://doi.org/10.1016/j.euf.2016.10.008
- Treatment sequencing in metastatic castrate-resistant prostate cancer.Asian J Androl. 2014; 16: 426-431https://doi.org/10.4103/1008-682X.126378
- Prostate cancer in elderly men.Rev Urol. 2008; 10 ([PubMed PMID: 18660852]): 111-119
- Challenges of managing elderly men with prostate cancer.Nat Rev Clin Oncol. 2014; 11: 354-364https://doi.org/10.1038/nrclinonc.2014.71
- Older adult participation in cancer clinical trials: a systematic review of barriers and interventions.CA Cancer J Clin. 2021; 71: 78-92https://doi.org/10.3322/caac.21638
- The application of the principles of geriatrics to the management of the older person with cancer.Crit Rev Oncol Hematol. 2000; 35: 147-154https://doi.org/10.1016/s1040-8428(00)00089-5
- Age and clinical decision making in oncology patients.J Natl Cancer Inst. 1994; 86: 1766-1770https://doi.org/10.1093/jnci/86.23.1766
- Patient-defined goals and preferences among older adults with cancer starting chemotherapy (CT).J Clin Oncol. 2018; 36: 10009https://doi.org/10.1200/JCO.2018.36.15_suppl.10009
- Modifiable factors affecting older patients’ quality of life and physical function during cancer treatment.J Geriatr Oncol. 2019; 10: 904-912https://doi.org/10.1016/j.jgo.2019.08.001
- Patient preferences for treatment outcomes in oncology with a focus on the older patient – a systematic review.Cancers (Basel). 2022; 14: 1147https://doi.org/10.3390/cancers14051147
- Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology.BJU Int. 2010; 106: 462-469https://doi.org/10.1111/j.1464-410X.2010.09334.x
- The identification of frailty: a systematic literature review.J Am Geriatr Soc. 2011; 59: 2129-2138https://doi.org/10.1111/j.1532-5415.2011.03597.x
- Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156https://doi.org/10.1093/gerona/56.3.m146
- Frailty and cancer: implications for oncology surgery, medical oncology, and radiation oncology.CA Cancer J Clin. 2017; 67: 362-377https://doi.org/10.3322/caac.21406
- Association between the baseline frailty and quality of life in patients with prostate cancer (FRAQ-PC study).Int J Clin Oncol. 2021; 26: 199-206https://doi.org/10.1007/s10147-020-01798-4
- Screening older cancer patients: first evaluation of the G-8 geriatric screening tool.Ann Oncol. 2012; 23: 2166-2172https://doi.org/10.1093/annonc/mdr587
- Screening for vulnerability in elderly cancer patients: validation of the G8 screening test.PLoS One. 2014; 9e115060https://doi.org/10.1371/journal.pone.0115060
- The vulnerable elders survey: a tool for identifying vulnerable older people in community.J Am Geriatric Soc. 2001; 49: 1691-1699https://doi.org/10.1046/j.1532-5415.2001.49281.x
- Association of chemotherapy, enzalutamide, abiraterone, and radium 223 with cognitive function in older men with metastatic castration-resistant prostate cancer.JAMA Netw Open. 2021; 4e2114694https://doi.org/10.1001/jamanetworkopen.2021.14694
- Examining the ability of the cancer and aging research group tool to predict toxicity in older men receiving chemotherapy or androgen-receptor-targeted therapy for metastatic castration-resistant prostate cancer.Cancer. 2021; 127: 2587-2594https://doi.org/10.1200/JCO.2019.37.15_suppl.11510
- Accumulation of deficits as a proxy measure of aging.The Scientific World. 2001; 1: 323-336https://doi.org/10.1100/tsw.2001.58
- A standard procedure for creating a frailty index.BMC Geriatr. 2008; 8: 24https://doi.org/10.1186/1471-2318-8-24
- Frailty index developed from a cancer-specific geriatric assessment and the association with mortality among older adults with cancer.J Natl Compr Canc Netw. 2017; 15: 894-902https://doi.org/10.6004/jnccn.2017.0122
- Assessment of muscle function and physical performance in daily clinical practice: a position paper endorsed by the European Society for Clinical and Economic aspects of Osteoporosis, Ostearthritis, and Musculoskeletal Diseases (ESCEO).Calcif Tissue Int. 2019; 105: 1-14https://doi.org/10.1007/s00223-019-00545-w
- The Functional Assessment of Cancer Therapy scale: development and validation of the general measure.J Clin Oncol. 1993; 11: 570-579https://doi.org/10.1200/JCO.1993.11.3.570
- The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients.J Palliat Care. 1991; 7 ([PubMed PMID: 1714502]): 6-9
- Monitoring depression treatment outcomes with the patient health questionnaire-9.Med Care. 2004; 42: 1194-1201https://doi.org/10.1097/00005650-200412000-00006
- Physical performance measures for predicting outcome in cancer patients: a systematic review.Acta Oncol. 2016; 55: 1386-1391https://doi.org/10.1080/0284186X.2016.1219047
- Assessment of older people: self-maintaining and instrumental activities of daily living.Gerontologist. 1969; 9 ([PubMed PMID: 5349366]): 179-186
- No adjustments are needed for multiple comparisons.Epidemiology. 1990; 1 ([PubMed PMID: 2081237]): 43-46
- Impact of treatment on elder-relevant physical function and quality of life outcomes in older adults with metastatic castration-resistant prostate cancer.JGO. 2022; https://doi.org/10.1016/j.jgo.2022.10.010
- A prospective study examining elder-relevant outcomes in older adults with prostate cancer undergoing treatment with chemotherapy or abiraterone.J Geriatr Oncol. 2016; 7: 81-89https://doi.org/10.1016/j.jgo.2016.01.003
- Comparison of prostate cancer with and without pain.Pain. 1993; 53: 159-162https://doi.org/10.1016/0304-3959(93)90075-Z
- Pain predicts overall survival in men with metastatic castration-refractory prostate cancer.J Clin Oncol. 2008; 26: 2544-2549https://doi.org/10.1200/JCO.2007.15.0367
- Cognition and depression effects of androgen receptor axis-targeted drugs in men with prostate cancer: a systematic review.J Geriatr Oncol. 2021; 12: 687-695https://doi.org/10.1016/j.jgo.2020.11.002
- Quality of life and emotional distress in advanced prostate cancer survivors undergoing chemotherapy.Health Qual Life Outcomes. 2004; 2: 37https://doi.org/10.1186/1477-7525-2-37
- Integrated analysis of pain, health-related quality of life, and analgesic use in patients with metastatic castration-resistant prostate cancer treated with radium-223.Prostate Cancer Prostatic Dis. 2022; 25: 248-255https://doi.org/10.1038/s41391-021-00412-6
- Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients.Eur J Cancer. 2019; 116: 116-136https://doi.org/10.1016/j.ejca.2019.04.031
- Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review.Lancet Oncol. 2012; 13: e437-e444https://doi.org/10.1016/S1470-2045(12)70259-0
- A scoping review of the Clinical Frailty Scale.BMC Geriatr. 2020; 20: 393https://doi.org/10.1186/s12877-020-01801-7
- A road map for the recruitment and retention of older adult participants for longitudinal studies.J Am Geriatr Soc. 2010; 58: 5303-5307
- Recruitment and retention of older people in clinical research: a systematic literature review.J Am Geriatr Soc. 2020; 68: 2955-2963
- Use of geriatric assessment and screening tools of frailty in elderly patients with prostate cancer.Review Aging Male. 2017; 20: 102-109https://doi.org/10.1080/13685538.2016.1277516
- Decision making in older adults with cancer.J Clin Oncol. 2021; 39: 2164-2174https://doi.org/10.1200/JCO.21.00165
- Geriatric assessment-driven intervention (GAIN) on chemotherapy-related toxic effects in older adults with cancer: a randomized clinical trial.JAMA Oncol. 2021; 7e214158https://doi.org/10.1001/jamaoncol.2021.4158
- Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.Lancet. 2021; 398: 1894-1904https://doi.org/10.1016/S0140-6736(21)01789-X
Article info
Publication history
Published online: January 20, 2023
Accepted:
December 6,
2022
Received in revised form:
December 1,
2022
Received:
July 19,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
