- Email: [email protected]
Geriatric Assessment in Elderly Patients with Prostate Cancer
Original Contribution
Geriatric Assessment in Elderly Patients with Prostate Cancer Catherine Terret1 Gilles Albrand2 Jean Pierre Droz1
Abstract
1Geriatric
Oncology Program, Centre Léon Bérard, Lyon, France 2Comprehensive Geriatric Assessment Unit, Hôpital Gériatrique Antoine Charial Francheville, France
Clinical Prostate Cancer, Vol. 2, No. 4, 236-240, 2004 Key words: Geriatric oncology, Prostatectomy, Radiation therapy, Quality of life
Submitted: Nov 5, 2003; Revised: Jan 12, 2004 Accepted: Jan 13, 2004
Introduction
Address for correspondence: Catherine Terret, MD, PhD Medical Oncology Department Centre Léon Bérard 28, rue Laennec 69373 Lyon Cedex 08 France Fax: 33-47878-2716 e-mail: [email protected] Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1540-0352, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
236 • Clinical
Prostate Cancer
As a result of demographic evolution, oncologists will treat more and more elderly patients with prostate cancer. Aging is frequently associated with the coexistence of several medical complications that can increase the complexity of cancer treatment decision-making. Unfortunately, clinical oncologists need to be more familiar with the multidimensional assessment of elderly patients. To acquire this skill, we implemented a multidimensional geriatric assessment program at our cancer center. This instrument prospectively assessed 60 elderly patients with prostate cancer. Herein, we describe geriatric aspects detected in our patient sample and report treatment options proposed to elderly patients with prostate cancer at different disease stages. The minimal comprehensive geriatric assessment (mini-CGA) procedure revealed that 66% of our patient population was dependent in one or more of the Katz Activities of Daily Living and 87% were dependent in 1 or more of the Lawton Instrumental Activities of Daily Living; all patients had significant comorbidity according to the Cumulative Illness Rating Scale–Geriatrics, 75% having at least one severe comorbidity. We identified 19 cases of drug interaction. We also observed that half of these patients had a risk of falling and some physical disability; 45% had cognitive disorders requiring more investigation; one third had depressive symptoms. Finally, 65% of the patients were either malnourished or at risk of malnutrition. Many of these problems were unknown before the mini-CGA processing and may interfere with cancer and cancer treatment. Thus, the correct management of elderly patients with cancer requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis. This approach will help us to propose the most appropriate treatment with the main aim of preserving quality of life.
Prostate cancer represents the most common cancer in men aged ≥ 70 years.1 Although in the past, many patients had advanced-stage cancer at diagnosis, we observe more and more older patients with tumors localized within the prostate. Therefore, we should consider the management of elderly patients with different disease stages. Nevertheless, the management of this kind of tumor is typically based on a balance between the maintenance of quality of life (QOL) and longevity of life. Prostate cancer treatment can cause severe side effects, especially in elderly patients. These side effects may alter their QOL for an extended period of time. Conversely, the therapeutic strategy must take the survival likelihood of elderly patients into consideration, as people in Western countries live longer today than they have in the past.2 The survival likelihood of elderly patients with cancer is not only related to cancer severity, but also to the patients’ global health status, and particularly to other medical conditions. Unfortunately, aging is high-
March 2004
Geriatric Assessment in Prostate Cancer ly individualized, with a loss of function reserve3 that cannot always be identified by conventional medical examination. Geriatricians have developed a multidimensional geriatric assessment tool to appraise the real health status of elderly people.4 This procedure is considered to be more effective than standard medical evaluation.5 Therefore, a comprehensive geriatric assessment is recommended as the basis for planning treatment of elderly patients with cancer.6 Thus, the management of prostate cancer in elderly patients requires a relevant staging of their malignant disease and a relevant geriatric assessment. In the past few years, we have developed a geriatric oncology program with the aim to optimize the management of elderly patients with cancer seen at our institution. This program combines conventional assessment of the patient’s disease stage and geriatric assessment in order to offer patients the most appropriate treatment possible. The objective of this work was to retrospectively describe patient characteristics identified by our program. We focused our attention on elderly patients with prostate cancer who were prospectively evaluated through our geriatric oncology program.
Patients and Methods From 1999 to 2001, patients ≥ 65 years of age with a diagnosis of prostate cancer were proposed to be included in our geriatric oncology program. Most of these patients were admitted at our institution for the management of advanced-stage disease. Information on the malignant disease was collected with attention to the first appearance of cancer (time, stage, first-line treatment scheme). Data were obtained through an adapted version of the geriatric multidimensional assessment tool, which we have called the minimal comprehensive geriatric assessment (mini-CGA).7 This procedure has been designed to collect information on several major domains including medical (comorbidity), functional, cognitive, affective, social, and environmental aspects. It is essentially based on a very careful medical examination. We also used other evaluation tools previously validated in elderly people. Dependence was measured with use of 3 tools: the Katz Activities of Daily Living (ADLs) scale,8 which focuses on 6 basic activities of daily living (bathing, dressing, toileting, transferring, continence, and feeding); the Lawton Instrumental Activities of Daily Living (IADLs) scale,9 which appraises more complex activities essential for independence in community residence; and the Karnofsky Performance Scale (PS), which is widely used in the oncology setting to subjectively appreciate performance status.10 The Folstein Mini Mental State Examination (MMSE) was used to evaluate patients’ cognitive status.11 Depressive symptoms were detected with the Geriatric Depression Scale (GDS).12 Nutritional status was assessed through the Mini Nutritional Assessment (MNA).13 The Performance-Oriented Assessment of Mobility instrument provided information on patients’ physical ability and fall risk.14 Comorbidity that corresponds to all medical conditions a patient may have, excluding the disease of primary interest,15 was assessed with use of the Cumulative Illness Rating Scale–Geriatrics (CIRS-G).16,17 This scale classifies comorbid
Table 1 Geriatric Characteristics of Patients Comprehensive Geriatric Assessment Median Age, Years (Range)
No. of Patients (N = 60) 78 (68-92)
Living Alone
11 (18%)
Reliable Caregiver Available
46 (77%)
Six Activities of Daily Living (Fully Independent)
20 (33%)
Instrumental Activities of Daily Living 14 (Fully independent)
8 (13%)
≥ 11 (Dependent for housekeeping)
12 (20%)
Karnofsky Performance Scale 80%-100% (ECOG PS 0/1)
22 (37%)
60%-70% (ECOG PS 2)
29 (48%)
< 60% (ECOG PS > 2)
9 (15%)
Mini Nutritional Assessment > 23.5 (Well nourished)
21 (35%)
17-23.5 (At risk for malnutrition)
27 (45%)
< 17 (Malnourished)
12 (20%)
Mini Mental State Examination Score > 24 (Normal Cognitive Status)
33 (55%)
Geriatric Depression Scale < 15 (No signs of depression) > 22 (Depression)
40 (67%) 2 (3%)
Mobility Normal
28 (47%)
Unrealizable test result
11 (18%)
Abbreviation: ECOG PS = Eastern Cooperative Oncology Group Performance Status
events by organ system affected and rates their severity on a scale of 0-4, with a grading similar to that of the Common Toxicity Criteria scale (none, mild, moderate, severe, extremely severe/life-threatening). This scale has 14 organ system categories and collects information such as the total number of categories involved, total score, severity index (total score divided by total number of categories involved), the number of categories at level 3 severity, and the number of categories at level 4 severity. We also assessed biologic function through analysis of the following parameters: hemoglobin, white blood cell count and differential count, creatinine clearance, and serum albumin level. A multidisciplinary team, including a geriatrician, a medical oncologist (geriatrics certified), a social worker, a dietician, a physiotherapist, a pharmacist, and a research nurse performed the mini-CGA. Each mini-CGA evaluation lasts 90-120 minutes. At the end of assessment, the geriatrician and oncologist created an inventory of the different problems identified and proposed an individualized intervention program with specific advice on cancer treatment options.
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Geriatric Assessment in Prostate Cancer
Figure 1 Distribution of Comorbidity Score and Categories 20
Patients (%)
15 10 5 0
2-3
4-5
6-7
8-9 10-11 12-13 14-15 16-17 18 20-21 23
25
CIRS-G Total Score 20
Patients (%)
15 10 5 0
1
2
3
4
5
6
7
8
9
10
CIRS-G Categories
Abbreviation: CIRS-G = Cumulative Illness Rating Scale–Geriatrics
Table 2 First-Line Therapy of Patients with Local Prostate Cancer at Diagnosis of Treatment Option Number Patients
Radical Prostatectomy
7
Irradiation
5
Cyproterone acetate
2
External Irradiation
13
Alone
6
Cyproterone acetate
3
CAB
2
Castration
2
Disease Stage
Median Age, Years (Range)
T1c-T3c N0 M0 69.5 (62-74.5)
T1c-T3 N0 M0
65.5 (59-79)
Brachytherapy + CAB
1
T2b N0 M0
68
Hormone Therapy
14
T1b-T4 N0 M0
73 (63-84)
CAB
6
Castration
6
Other
2
No Therapy
2
Total
37
Abbreviation: CAB = complete androgen blockade
238 • Clinical
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March 2004
Results Minimal Comprehensive Geriatric Assessment Data Sixty patients with prostate cancer were included in our geriatric oncology program. Their characteristics are shown in Table 1. The median age was 78 years (range, 68-92 years). Only 11 patients (18%) lived alone and 46 patients (77%) had a reliable caregiver. Twenty patients (33%) were totally independent in ADLs (n = 6). Eight patients were completely independent in IADLs (n = 14). The median Karnofsky PS score was 70% (10%100%). Nine patients had a poor PS of < 60%, corresponding to a Eastern Cooperative Oncology Group (ECOG) PS > 2, and approximately half of the patients had a Karnofsky PS of 60%70%, (ie, ECOG PS 2). The MMSE score was > 24, and therefore considered normal, in 33 patients. Sixteen patients (27%) had symptoms of depression (GDS > 15). The Performance-Oriented Assessment of Mobility could not be performed in 11 patients because of severe disability. Twenty-eight patients (47%) had no physical limitation. Only one third of patients were well nourished, whereas 27 patients were at risk of malnutrition and 12 were already malnourished. Median serum albumin levels were 3.0 g/dL, 3.6 g/dL, and 4.1 g/dL, respectively, in the 3 MNA groups. The median peripheral lymphocyte count was 1250 cells/μL (range, 400-6880) for patients with MNA scores > 23.5 and 950 cells/μL (range, 290-2200) for patients with MNA scores ≤ 23.5. According to the CIRS-G scale, all patients had ≥ 3 comorbid conditions, with a median of 7 (range, 3-12; Figure 1). The median total score was 13 (range, 3-25), the median severity index was 1.88 (range, 1-2.86), and the median number of severe comorbidities was 1 (0-9 comorbidities). Furthermore, patients took a median of 5 medications (range, 0-13 medications). We identified 19 cases of dangerous drug interactions.
Initial Treatment of Patients with Prostate Cancer We reviewed the initial treatment of patients who subsequently underwent mini-CGA. On the date of diagnosis of prostate cancer, 37 patients had local disease, 18 had metastatic disease, and initial disease stage was unknown for the remaining 5 patients. Patients with local prostate cancer initially received various treatment options, which are presented in Table 2. Seven patients with clinical stage T1c-T3c N0 M0 disease underwent radical prostatectomy. Five of these also received adjuvant external-beam radiation. Thirteen patients were treated with external irradiation with or without androgen deprivation. One patient was a candidate for brachytherapy and complete androgen blockade (CAB). Fourteen patients had only androgen deprivation and 2 patients, despite their local disease status, had no specific treatment. All patients with metastatic disease were treated with hormone therapy; 8 patients underwent CAB, 8 underwent castration, and 2 were treated with cyproterone acetate. Of the 5 patients with unknown initial disease stage, 2 underwent castration, 1 underwent CAB, 1 underwent cyproterone acetate therapy, and 1 had no specific treatment.
Catherine Terret et al Prostate Cancer Status on the Day of Minimal Comprehensive Geriatric Assessment On the day of mini-CGA, 46 patients (77%) had metastatic prostate cancer, half of whom had only bone metastasis. Seven patients had local or locally advanced disease and 5 patients had locally advanced disease and elevated prostate-specific antigen (PSA) levels without evidence of metastasis. At the end of miniCGA, patients could be given cancer treatment advice (Table 3). In case of local or locally advanced prostate cancer, we proposed radiation therapy (n = 4 patients) or hormone therapy (n = 2) or watchful waiting (n = 1). When patients had only biologic proof of progression (ie, elevated PSA level), we generally did not modify treatment in progress. Concerning patients with metastatic prostate cancer, our treatment recommendations varied depending on clinical symptoms and included transurethral resection (n = 2), metastasis irradiation (n = 6), radiopharmaceuticals (n = 2), bone metastasis surgery (n = 1), hormone therapy (n = 10), chemotherapy (n = 15). Three of these 15 patients were included in a clinical trial. We did not provide any recommendation for 10 patients with metastatic disease.
Discussion The management of elderly patients with prostate cancer is a prominent issue in oncology. We must take into account the increasing incidence of prostate cancer and the increasing life expectancy of elderly patients. Unfortunately, the prolongation of life is associated with more medical problems, especially loss of functional independence and comorbidity. Thus, the management of prostate cancer should be individualized to provide benefits to all elderly people. We studied patients aged ≥ 65 years with prostate cancer from a geriatric oncologic point of view. The median age of our study population was 78 years and the youngest patient was 68 years of age. The mini-CGA procedure performed among this population revealed that 66% of the patients were dependent in ≥ 1 ADLs and 87% were dependent in ≥ 1 IADLs; all patients had significant comorbidity according to the CIRS-G scale, 75% having ≥ 1 severe comorbidity. We observed no clear relationship among the level of dependence assessed by ADL scale, the extent of disease, and the severity of comorbidity. The distribution of patients with metastatic prostate cancer or severe comorbidity was not parallel to the increase of the dependence level. We identified 19 cases of dangerous drug interaction. We also observed that half of these patients had a risk of falling and some physical disability, 45% had cognitive disorders requiring more investigation, and one third had depressive symptoms. Finally, 65% of the patients were malnourished or at risk of malnutrition. Many of these problems were unknown before the miniCGA processing. The final recommendations program was elaborated from these data to help patients and caregivers cope with these newly identified frailty factors. The detection of medical problems other than cancer has already been underlined by other geriatric oncology teams.18 Repetto et al also demonstrated that the assessment of patient functional status by means of Karnofsky PS does not provide sufficient data when this tool is applied to elderly patients.19 All information described previ-
Table 3 Cancer Treatment Recommendations Based on Mini-CGA
Disease Status Local/Locally Advanced Disease
Median Age, Years (Range)
Number of Patients
77 (72-81)
7
Prostate radiation therapy
4
Hormone therapy
2
Watchful waiting
1
Biologic Failure
81 (73.5-92)
No treatment
5
Hormone therapy Advanced Prostate Cancer
6
1 78 (68-87.5)
46
Bone metastasis surgery
1
Transurethral resection
2
Radiopharmaceuticals
2
Palliative radiation therapy
6
Hormonal therapy
10
Chemotherapy
15
No treatment Unknown Stage
10 79.5
No treatment
1 1
Abbreviation: CGA = comprehensive geriatric assessment
ously must be kept in mind at the time of treatment decisionmaking. However, the complexity of this time-consuming procedure is an obstacle to its widespread use. Thus, we are currently searching and testing a specific screening tool with the aim to screen patients with cancer who should benefit from mini-CGA.20 From an oncologic point of view, most patients (n = 46) had metastatic prostate cancer when they were admitted in our geriatric oncology program. In addition to geriatric recommendations, palliative treatment was sometimes required to improve patient QOL.21 Radiopharmaceuticals, palliative radiation therapy, and chemotherapy could be proposed to these patients depending on their disease status and geriatric parameters. Three patients could be enrolled in clinical trials despite their chronologic advanced age; older patients are usually not included in trials.22 By means of the mini-CGA, we were able to characterize the physiologic age of these older patients, which is poorly reflected by chronologic age. The mini-CGA is a reliable instrument for assessing aging that allows the design of clinical trials involving older people. More recently, patients with local disease were also admitted in our program. Should these elderly patients be treated with curative intent? Surgery or radiation therapy with curative intent is recommended if the estimated malignant potential of the disease and estimated longevity of the patient suggest a high risk of metastatic progression during the remainder of the patient’s lifetime. When we considered our sample of patients, 4 had a
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Geriatric Assessment in Prostate Cancer tumor that was clinically confined to the prostate and miniCGA failed to detect any major geriatric problem or frailty factor. According to the classification of Balducci and Extermann,18 they could thus receive standard treatment similar to that given younger patients. In fact, only 2 patients with T2b N0 M0 prostate cancer were treated with external-beam radiation. One patient with T1c N0 M0 prostate cancer was undergoing watchful waiting. The last patient with T2b N0 M0 tumor was treated with hormone suppression; however, this patient had previously been treated for stage B colon cancer. From this experience, it becomes obvious that the management of older patients with localized prostate cancer represents a real problem in geriatric oncology. Since PSA detection methods have been available, we have observed a marked increase in the rate of newly diagnosed localized prostate cancers.23 Conversely, the number of patients with advanced disease at diagnosis is rapidly decreasing. This incidence evolution leads to an evolution of patterns of care; more patients are treated with curative intent with radical prostatectomy or radiation therapy.23 In our institution, the management of elderly patients with localized prostate cancer has also evolved. A few years ago, treatment with curative intent was never proposed to patients ≥ 75 years of age. Nowadays, age is no longer considered a pivotal criterion for proposing curative radiation therapy. The main criteria is a patient’s likelihood to live > 10 years, independently of chronologic age. The longevity of elderly people depends not only on the status of their prostate cancer, but also on concomitant medical conditions. Therefore, CGA that represents a reliable way to approach the life expectancy of elderly patients may be proposed in the future to improve treatment decision-making. The next step of our research will be to evaluate the impact on patient outcomes of interventions performed to correct health abnormalities revealed by the mini-CGA procedure.
Conclusion As life expectancy continues to increase, the number of older patients with prostate cancer will continue to increase, representing a critical therapeutic issue for oncologists. The correct management of these patients requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis. This approach will help us to propose the most appropriate treatment with the main emphasis of preserving QOL. However, curative strategies should not be delayed whenever the estimated survival probability is compatible with theoretical curative treatment indications.
240 • Clinical
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March 2004
Acknowledgement The authors thank Marie-Dominique Reynaud for careful editing of this article.
References 1. Edwards BK, Howe HL, Ries LAG, et al. Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden. Cancer 2002; 94:2766-2792. 2. Yancik R, Ries LAG. Aging and cancer in America: demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 2000; 14:17-23. 3. Shock NW. Aging and physiological systems. J Chron Dis 1983; 36:137-142. 4. Reuben D. Geriatric assessment in oncology. Cancer 1997; 80:1311-1313. 5. Stuck AE, Siu AL, Wieland GD, et al. Comprehensive geriatric assessment: a meta-analysis of controlled trials. Lancet 1993; 342:1032-1036. 6. Balducci L, Yates J. General guidelines for the management of older patients with cancer. Oncology 2000; 14:221-227. 7. Terret C, Gaujard S, Droz JP. Current views in geriatric oncology. Bull Cancer 2003; 90:93-96. 8. Katz S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963; 185:914-919. 9. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969; 9:179-186. 10. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, ed, Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press, 1949: 196-205. 11. Folstein MF, Folstein SE, McHugh PR. “Mini Mental State”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189-198. 12. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982-1983; 17:37-49. 13. Guigoz Y, Vellas B, Garry PJ. assessing nutritional status of the elderly. The Mini-Nutritional Assessment as part of the geriatric evaluation. Nutr Rev 1996; 54(suppl):S59-S65. 14. Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc 1986; 34:119-126. 15. Greenfield S, Nelson EC. Recent developments and future issues in the use of health status assessment measures in clinical settings. Med Care 1992; 30:MS23-MS41. 16. Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc 1968; 16:622-626. 17. Miller MD, Towers A. A Manual of Guidelines for Scoring the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Pittsburgh, PA: Western Psychiatric Institute and Clinic, University of Pittsburgh, 1991. 18. Balducci L, Extermann M. Management of cancer in the older person: a practical approach. The Oncologist 2000; 5:224-237. 19. Repetto L, Fratino L, Audisio RA, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group Performance Status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 2002; 20:494-502. 20. Terret C, Albrand G, Moncenix G, et al. Geriatric Oncology: screening for older frail cancer patients (pts), Karnofsky Performance Scale (KPS) or Physical Performance Test (PPT)? Proc Am Soc Clin Oncol 2003; 22:728 (Abstract #2929). 21. Droz JP, Fléchon A, Terret C. Prostate cancer, management of advanced disease. Ann Oncol 2002; 13(suppl 4):89-94. 22. Monfardini S, Sorio R, Boes GH, et al. Entry and evaluation of elderly patients in European Organization for Research and Treatment of Cancer (EORTC) new-drug-development studies. Cancer 1995; 76:333-338. 23. Dennis LK, Resnick MI. Analysis of recent trends in prostate cancer incidence and mortality. Prostate 2000; 42:247-252.
Geriatric Assessment in Elderly Patients with Prostate Cancer Catherine Terret1 Gilles Albrand2 Jean Pierre Droz1
Abstract
1Geriatric
Oncology Program, Centre Léon Bérard, Lyon, France 2Comprehensive Geriatric Assessment Unit, Hôpital Gériatrique Antoine Charial Francheville, France
Clinical Prostate Cancer, Vol. 2, No. 4, 236-240, 2004 Key words: Geriatric oncology, Prostatectomy, Radiation therapy, Quality of life
Submitted: Nov 5, 2003; Revised: Jan 12, 2004 Accepted: Jan 13, 2004
Introduction
Address for correspondence: Catherine Terret, MD, PhD Medical Oncology Department Centre Léon Bérard 28, rue Laennec 69373 Lyon Cedex 08 France Fax: 33-47878-2716 e-mail: [email protected] Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1540-0352, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
236 • Clinical
Prostate Cancer
As a result of demographic evolution, oncologists will treat more and more elderly patients with prostate cancer. Aging is frequently associated with the coexistence of several medical complications that can increase the complexity of cancer treatment decision-making. Unfortunately, clinical oncologists need to be more familiar with the multidimensional assessment of elderly patients. To acquire this skill, we implemented a multidimensional geriatric assessment program at our cancer center. This instrument prospectively assessed 60 elderly patients with prostate cancer. Herein, we describe geriatric aspects detected in our patient sample and report treatment options proposed to elderly patients with prostate cancer at different disease stages. The minimal comprehensive geriatric assessment (mini-CGA) procedure revealed that 66% of our patient population was dependent in one or more of the Katz Activities of Daily Living and 87% were dependent in 1 or more of the Lawton Instrumental Activities of Daily Living; all patients had significant comorbidity according to the Cumulative Illness Rating Scale–Geriatrics, 75% having at least one severe comorbidity. We identified 19 cases of drug interaction. We also observed that half of these patients had a risk of falling and some physical disability; 45% had cognitive disorders requiring more investigation; one third had depressive symptoms. Finally, 65% of the patients were either malnourished or at risk of malnutrition. Many of these problems were unknown before the mini-CGA processing and may interfere with cancer and cancer treatment. Thus, the correct management of elderly patients with cancer requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis. This approach will help us to propose the most appropriate treatment with the main aim of preserving quality of life.
Prostate cancer represents the most common cancer in men aged ≥ 70 years.1 Although in the past, many patients had advanced-stage cancer at diagnosis, we observe more and more older patients with tumors localized within the prostate. Therefore, we should consider the management of elderly patients with different disease stages. Nevertheless, the management of this kind of tumor is typically based on a balance between the maintenance of quality of life (QOL) and longevity of life. Prostate cancer treatment can cause severe side effects, especially in elderly patients. These side effects may alter their QOL for an extended period of time. Conversely, the therapeutic strategy must take the survival likelihood of elderly patients into consideration, as people in Western countries live longer today than they have in the past.2 The survival likelihood of elderly patients with cancer is not only related to cancer severity, but also to the patients’ global health status, and particularly to other medical conditions. Unfortunately, aging is high-
March 2004
Geriatric Assessment in Prostate Cancer ly individualized, with a loss of function reserve3 that cannot always be identified by conventional medical examination. Geriatricians have developed a multidimensional geriatric assessment tool to appraise the real health status of elderly people.4 This procedure is considered to be more effective than standard medical evaluation.5 Therefore, a comprehensive geriatric assessment is recommended as the basis for planning treatment of elderly patients with cancer.6 Thus, the management of prostate cancer in elderly patients requires a relevant staging of their malignant disease and a relevant geriatric assessment. In the past few years, we have developed a geriatric oncology program with the aim to optimize the management of elderly patients with cancer seen at our institution. This program combines conventional assessment of the patient’s disease stage and geriatric assessment in order to offer patients the most appropriate treatment possible. The objective of this work was to retrospectively describe patient characteristics identified by our program. We focused our attention on elderly patients with prostate cancer who were prospectively evaluated through our geriatric oncology program.
Patients and Methods From 1999 to 2001, patients ≥ 65 years of age with a diagnosis of prostate cancer were proposed to be included in our geriatric oncology program. Most of these patients were admitted at our institution for the management of advanced-stage disease. Information on the malignant disease was collected with attention to the first appearance of cancer (time, stage, first-line treatment scheme). Data were obtained through an adapted version of the geriatric multidimensional assessment tool, which we have called the minimal comprehensive geriatric assessment (mini-CGA).7 This procedure has been designed to collect information on several major domains including medical (comorbidity), functional, cognitive, affective, social, and environmental aspects. It is essentially based on a very careful medical examination. We also used other evaluation tools previously validated in elderly people. Dependence was measured with use of 3 tools: the Katz Activities of Daily Living (ADLs) scale,8 which focuses on 6 basic activities of daily living (bathing, dressing, toileting, transferring, continence, and feeding); the Lawton Instrumental Activities of Daily Living (IADLs) scale,9 which appraises more complex activities essential for independence in community residence; and the Karnofsky Performance Scale (PS), which is widely used in the oncology setting to subjectively appreciate performance status.10 The Folstein Mini Mental State Examination (MMSE) was used to evaluate patients’ cognitive status.11 Depressive symptoms were detected with the Geriatric Depression Scale (GDS).12 Nutritional status was assessed through the Mini Nutritional Assessment (MNA).13 The Performance-Oriented Assessment of Mobility instrument provided information on patients’ physical ability and fall risk.14 Comorbidity that corresponds to all medical conditions a patient may have, excluding the disease of primary interest,15 was assessed with use of the Cumulative Illness Rating Scale–Geriatrics (CIRS-G).16,17 This scale classifies comorbid
Table 1 Geriatric Characteristics of Patients Comprehensive Geriatric Assessment Median Age, Years (Range)
No. of Patients (N = 60) 78 (68-92)
Living Alone
11 (18%)
Reliable Caregiver Available
46 (77%)
Six Activities of Daily Living (Fully Independent)
20 (33%)
Instrumental Activities of Daily Living 14 (Fully independent)
8 (13%)
≥ 11 (Dependent for housekeeping)
12 (20%)
Karnofsky Performance Scale 80%-100% (ECOG PS 0/1)
22 (37%)
60%-70% (ECOG PS 2)
29 (48%)
< 60% (ECOG PS > 2)
9 (15%)
Mini Nutritional Assessment > 23.5 (Well nourished)
21 (35%)
17-23.5 (At risk for malnutrition)
27 (45%)
< 17 (Malnourished)
12 (20%)
Mini Mental State Examination Score > 24 (Normal Cognitive Status)
33 (55%)
Geriatric Depression Scale < 15 (No signs of depression) > 22 (Depression)
40 (67%) 2 (3%)
Mobility Normal
28 (47%)
Unrealizable test result
11 (18%)
Abbreviation: ECOG PS = Eastern Cooperative Oncology Group Performance Status
events by organ system affected and rates their severity on a scale of 0-4, with a grading similar to that of the Common Toxicity Criteria scale (none, mild, moderate, severe, extremely severe/life-threatening). This scale has 14 organ system categories and collects information such as the total number of categories involved, total score, severity index (total score divided by total number of categories involved), the number of categories at level 3 severity, and the number of categories at level 4 severity. We also assessed biologic function through analysis of the following parameters: hemoglobin, white blood cell count and differential count, creatinine clearance, and serum albumin level. A multidisciplinary team, including a geriatrician, a medical oncologist (geriatrics certified), a social worker, a dietician, a physiotherapist, a pharmacist, and a research nurse performed the mini-CGA. Each mini-CGA evaluation lasts 90-120 minutes. At the end of assessment, the geriatrician and oncologist created an inventory of the different problems identified and proposed an individualized intervention program with specific advice on cancer treatment options.
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Figure 1 Distribution of Comorbidity Score and Categories 20
Patients (%)
15 10 5 0
2-3
4-5
6-7
8-9 10-11 12-13 14-15 16-17 18 20-21 23
25
CIRS-G Total Score 20
Patients (%)
15 10 5 0
1
2
3
4
5
6
7
8
9
10
CIRS-G Categories
Abbreviation: CIRS-G = Cumulative Illness Rating Scale–Geriatrics
Table 2 First-Line Therapy of Patients with Local Prostate Cancer at Diagnosis of Treatment Option Number Patients
Radical Prostatectomy
7
Irradiation
5
Cyproterone acetate
2
External Irradiation
13
Alone
6
Cyproterone acetate
3
CAB
2
Castration
2
Disease Stage
Median Age, Years (Range)
T1c-T3c N0 M0 69.5 (62-74.5)
T1c-T3 N0 M0
65.5 (59-79)
Brachytherapy + CAB
1
T2b N0 M0
68
Hormone Therapy
14
T1b-T4 N0 M0
73 (63-84)
CAB
6
Castration
6
Other
2
No Therapy
2
Total
37
Abbreviation: CAB = complete androgen blockade
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Results Minimal Comprehensive Geriatric Assessment Data Sixty patients with prostate cancer were included in our geriatric oncology program. Their characteristics are shown in Table 1. The median age was 78 years (range, 68-92 years). Only 11 patients (18%) lived alone and 46 patients (77%) had a reliable caregiver. Twenty patients (33%) were totally independent in ADLs (n = 6). Eight patients were completely independent in IADLs (n = 14). The median Karnofsky PS score was 70% (10%100%). Nine patients had a poor PS of < 60%, corresponding to a Eastern Cooperative Oncology Group (ECOG) PS > 2, and approximately half of the patients had a Karnofsky PS of 60%70%, (ie, ECOG PS 2). The MMSE score was > 24, and therefore considered normal, in 33 patients. Sixteen patients (27%) had symptoms of depression (GDS > 15). The Performance-Oriented Assessment of Mobility could not be performed in 11 patients because of severe disability. Twenty-eight patients (47%) had no physical limitation. Only one third of patients were well nourished, whereas 27 patients were at risk of malnutrition and 12 were already malnourished. Median serum albumin levels were 3.0 g/dL, 3.6 g/dL, and 4.1 g/dL, respectively, in the 3 MNA groups. The median peripheral lymphocyte count was 1250 cells/μL (range, 400-6880) for patients with MNA scores > 23.5 and 950 cells/μL (range, 290-2200) for patients with MNA scores ≤ 23.5. According to the CIRS-G scale, all patients had ≥ 3 comorbid conditions, with a median of 7 (range, 3-12; Figure 1). The median total score was 13 (range, 3-25), the median severity index was 1.88 (range, 1-2.86), and the median number of severe comorbidities was 1 (0-9 comorbidities). Furthermore, patients took a median of 5 medications (range, 0-13 medications). We identified 19 cases of dangerous drug interactions.
Initial Treatment of Patients with Prostate Cancer We reviewed the initial treatment of patients who subsequently underwent mini-CGA. On the date of diagnosis of prostate cancer, 37 patients had local disease, 18 had metastatic disease, and initial disease stage was unknown for the remaining 5 patients. Patients with local prostate cancer initially received various treatment options, which are presented in Table 2. Seven patients with clinical stage T1c-T3c N0 M0 disease underwent radical prostatectomy. Five of these also received adjuvant external-beam radiation. Thirteen patients were treated with external irradiation with or without androgen deprivation. One patient was a candidate for brachytherapy and complete androgen blockade (CAB). Fourteen patients had only androgen deprivation and 2 patients, despite their local disease status, had no specific treatment. All patients with metastatic disease were treated with hormone therapy; 8 patients underwent CAB, 8 underwent castration, and 2 were treated with cyproterone acetate. Of the 5 patients with unknown initial disease stage, 2 underwent castration, 1 underwent CAB, 1 underwent cyproterone acetate therapy, and 1 had no specific treatment.
Catherine Terret et al Prostate Cancer Status on the Day of Minimal Comprehensive Geriatric Assessment On the day of mini-CGA, 46 patients (77%) had metastatic prostate cancer, half of whom had only bone metastasis. Seven patients had local or locally advanced disease and 5 patients had locally advanced disease and elevated prostate-specific antigen (PSA) levels without evidence of metastasis. At the end of miniCGA, patients could be given cancer treatment advice (Table 3). In case of local or locally advanced prostate cancer, we proposed radiation therapy (n = 4 patients) or hormone therapy (n = 2) or watchful waiting (n = 1). When patients had only biologic proof of progression (ie, elevated PSA level), we generally did not modify treatment in progress. Concerning patients with metastatic prostate cancer, our treatment recommendations varied depending on clinical symptoms and included transurethral resection (n = 2), metastasis irradiation (n = 6), radiopharmaceuticals (n = 2), bone metastasis surgery (n = 1), hormone therapy (n = 10), chemotherapy (n = 15). Three of these 15 patients were included in a clinical trial. We did not provide any recommendation for 10 patients with metastatic disease.
Discussion The management of elderly patients with prostate cancer is a prominent issue in oncology. We must take into account the increasing incidence of prostate cancer and the increasing life expectancy of elderly patients. Unfortunately, the prolongation of life is associated with more medical problems, especially loss of functional independence and comorbidity. Thus, the management of prostate cancer should be individualized to provide benefits to all elderly people. We studied patients aged ≥ 65 years with prostate cancer from a geriatric oncologic point of view. The median age of our study population was 78 years and the youngest patient was 68 years of age. The mini-CGA procedure performed among this population revealed that 66% of the patients were dependent in ≥ 1 ADLs and 87% were dependent in ≥ 1 IADLs; all patients had significant comorbidity according to the CIRS-G scale, 75% having ≥ 1 severe comorbidity. We observed no clear relationship among the level of dependence assessed by ADL scale, the extent of disease, and the severity of comorbidity. The distribution of patients with metastatic prostate cancer or severe comorbidity was not parallel to the increase of the dependence level. We identified 19 cases of dangerous drug interaction. We also observed that half of these patients had a risk of falling and some physical disability, 45% had cognitive disorders requiring more investigation, and one third had depressive symptoms. Finally, 65% of the patients were malnourished or at risk of malnutrition. Many of these problems were unknown before the miniCGA processing. The final recommendations program was elaborated from these data to help patients and caregivers cope with these newly identified frailty factors. The detection of medical problems other than cancer has already been underlined by other geriatric oncology teams.18 Repetto et al also demonstrated that the assessment of patient functional status by means of Karnofsky PS does not provide sufficient data when this tool is applied to elderly patients.19 All information described previ-
Table 3 Cancer Treatment Recommendations Based on Mini-CGA
Disease Status Local/Locally Advanced Disease
Median Age, Years (Range)
Number of Patients
77 (72-81)
7
Prostate radiation therapy
4
Hormone therapy
2
Watchful waiting
1
Biologic Failure
81 (73.5-92)
No treatment
5
Hormone therapy Advanced Prostate Cancer
6
1 78 (68-87.5)
46
Bone metastasis surgery
1
Transurethral resection
2
Radiopharmaceuticals
2
Palliative radiation therapy
6
Hormonal therapy
10
Chemotherapy
15
No treatment Unknown Stage
10 79.5
No treatment
1 1
Abbreviation: CGA = comprehensive geriatric assessment
ously must be kept in mind at the time of treatment decisionmaking. However, the complexity of this time-consuming procedure is an obstacle to its widespread use. Thus, we are currently searching and testing a specific screening tool with the aim to screen patients with cancer who should benefit from mini-CGA.20 From an oncologic point of view, most patients (n = 46) had metastatic prostate cancer when they were admitted in our geriatric oncology program. In addition to geriatric recommendations, palliative treatment was sometimes required to improve patient QOL.21 Radiopharmaceuticals, palliative radiation therapy, and chemotherapy could be proposed to these patients depending on their disease status and geriatric parameters. Three patients could be enrolled in clinical trials despite their chronologic advanced age; older patients are usually not included in trials.22 By means of the mini-CGA, we were able to characterize the physiologic age of these older patients, which is poorly reflected by chronologic age. The mini-CGA is a reliable instrument for assessing aging that allows the design of clinical trials involving older people. More recently, patients with local disease were also admitted in our program. Should these elderly patients be treated with curative intent? Surgery or radiation therapy with curative intent is recommended if the estimated malignant potential of the disease and estimated longevity of the patient suggest a high risk of metastatic progression during the remainder of the patient’s lifetime. When we considered our sample of patients, 4 had a
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Geriatric Assessment in Prostate Cancer tumor that was clinically confined to the prostate and miniCGA failed to detect any major geriatric problem or frailty factor. According to the classification of Balducci and Extermann,18 they could thus receive standard treatment similar to that given younger patients. In fact, only 2 patients with T2b N0 M0 prostate cancer were treated with external-beam radiation. One patient with T1c N0 M0 prostate cancer was undergoing watchful waiting. The last patient with T2b N0 M0 tumor was treated with hormone suppression; however, this patient had previously been treated for stage B colon cancer. From this experience, it becomes obvious that the management of older patients with localized prostate cancer represents a real problem in geriatric oncology. Since PSA detection methods have been available, we have observed a marked increase in the rate of newly diagnosed localized prostate cancers.23 Conversely, the number of patients with advanced disease at diagnosis is rapidly decreasing. This incidence evolution leads to an evolution of patterns of care; more patients are treated with curative intent with radical prostatectomy or radiation therapy.23 In our institution, the management of elderly patients with localized prostate cancer has also evolved. A few years ago, treatment with curative intent was never proposed to patients ≥ 75 years of age. Nowadays, age is no longer considered a pivotal criterion for proposing curative radiation therapy. The main criteria is a patient’s likelihood to live > 10 years, independently of chronologic age. The longevity of elderly people depends not only on the status of their prostate cancer, but also on concomitant medical conditions. Therefore, CGA that represents a reliable way to approach the life expectancy of elderly patients may be proposed in the future to improve treatment decision-making. The next step of our research will be to evaluate the impact on patient outcomes of interventions performed to correct health abnormalities revealed by the mini-CGA procedure.
Conclusion As life expectancy continues to increase, the number of older patients with prostate cancer will continue to increase, representing a critical therapeutic issue for oncologists. The correct management of these patients requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis. This approach will help us to propose the most appropriate treatment with the main emphasis of preserving QOL. However, curative strategies should not be delayed whenever the estimated survival probability is compatible with theoretical curative treatment indications.
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Acknowledgement The authors thank Marie-Dominique Reynaud for careful editing of this article.
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