1 INTRODUCTION

Research has shown a negative impact of so-called “aggressive” care on the quality of life (QOL) of cancer patients at the advanced palliative phase.1-3 Earle et al. developed a set of quality indicators to assess the intensity of end-of-life care.4 However, to date, routine practice remains far from optimal in this regard. Chemotherapy near the end-of-life remains frequent, with 10% to 40% of cancer patients receiving a new chemotherapy line within 1 month of death.5-9 There is a compelling need to align practices with recommendations, through improved anticipation of the terminal phase, and de-escalation of the intensity of care as end-of-life approaches. To do this, a physician must be able to estimate how close the patient is to death, although it has been reported that oncologists tend to be overly optimistic in their estimations of life expectancy,10 over-estimating survival on average by a factor of 5.3.

To enable improved estimation of life expectancy in patients with cancer, several prognostic scores exist,11-18 and their use is widely established.18-20 Initially and primarily reserved for end-of-life patients,11, 21 some scores are now routinely used in patients still receiving curative therapy,15, 22 or at the early stages of palliative care.22 Yet, despite this proliferation of scores in recent years and the inclusion of some of them in national guidelines for supportive care in cancer,23-25 none of the key professional associations have accepted the complete integration of prognostic scores. Moreover, there is currently no international consensus regarding their role in patient management, or regarding which (if any) of the instruments should be recommended for use over another.

The aim of this study was to therefore describe the state of knowledge and the rate of use in routine practice of prognostic scores in advanced cancer. The primary objective was to evaluate the proportion of respondents who were aware of prognostic scales within their practice. The secondary objectives were: (i) to determine the proportion of respondents who use prognostic scores in their routine practice (frequency, circumstances, clinical utility); (ii) to determine the most widely known and frequently used scale(s); (iii) to investigate a potential relationship between the criteria included in the scores and the criteria applied by the respondents in their clinical practice to estimate life expectancy in patients with advanced cancer; and (iv) to assess respondents’ levels of interest in prognostic scales.

2 METHODS

A descriptive, cross-sectional, national survey was conducted and was available online for a period of 6 weeks from June 01 to July 12, 2020.

2.1 Study population

Respondents meeting all the following criteria were eligible to participate in the study: (i) Physicians registered with the national medical council, (ii) working in the field of oncology or palliative care, and (iii) holders of the appropriate nationally recognized qualifications in oncology or palliative care.

We excluded participants that meet the following noninclusion criteria: (i) respondents who were qualified in neither oncology nor palliative care, (ii) physicians working in pediatric oncology, and (iii) physicians working in hematology.

According to data provided by the national medical council, the total number of registered physicians meeting the inclusion criteria were 5112, of which 4492 were registered oncologists (medical oncologists and physicians from other specialties with qualifications enabling them to practice oncology within their specialty area), and 682 physicians registered in palliative care.

2.2 Study design and implementation

A link to an online questionnaire (LimeSurvey) was sent to all physicians who were registered specialists in either oncology or palliative care in France. The questionnaire was available online for completion from June 01 to July 12, 2020. Physicians were contacted through regional cancer care networks (N = 12), and through the mailing list of the French Society for Palliative Care (SFAP).

2.3 Data recorded in the questionnaire

The text of the questionnaire is provided in the Supplementary Material. The survey was sectioned into six parts. The first section collected sociodemographic data. The second section investigated the respondents’ knowledge of the five prognostic scales (Palliative Performance Status (PPS), Palliative Prognostic (PaP) Score, Palliative Prognostic Index (PPI), Glasgow Prognostic Score (GPS), and the Barbot score or Pronopall score). The level of knowledge was assessed on a three-level Likert scale, namely: (i) no knowledge (never heard of any of the instruments), (ii) limited knowledge (awareness that one or more of the scales exist, knows the names of one or more of the scales, knows some of the items included), and (iii) good knowledge (in-depth knowledge of at least one of the scales and its component criteria). Participants were also asked to indicate which sources they used to obtain information on the scales or about training about palliative care (such as guidelines and professional associations). Section three enquired about the respondents’ use of prognostic scales. For participants that answered “yes” to its use, they were asked to indicate the frequency of use on each scale that was declared (rarely, often, frequently, daily), and the context in which they used it (choice from among 14 proposals compiled from a review of literature - see Supplementary Material).

Participants were asked to indicate whether the prognostic scales were beneficial to them in their daily practice (never, sometimes, often, and always). Participants were also asked to indicate which scale they used most frequently. For self-declared nonusers, the obstacles to the use of scales were recorded (choice among 11 proposals, see Supplementary Material).

The fourth section enquired about the clinical relevance of the criteria in the prognostic scales. The aim of this section was to investigate whether the criteria cited by the physicians overlapped with those of the prognostic scales. A list of 12 criteria were provided including clinical, biological, social, and psychological characteristics and respondents were asked which ones they applied in their daily practice to estimate life expectancy. Some of the criteria proposed as response modalities were also present in the prognostic scores, while some were factors reported in literature to be determinant in decision-making among patients with advanced cancer.24

The last section of the questionnaire assessed the participants’ interest in prognostic scales. Participants were asked to respond using a 4-point Likert scale (strongly agree, agree, disagree, and strongly disagree) regarding: (i) whether the evaluation of patient prognosis was important; (ii) whether the prognostic scales were useful for the purpose; (iii) whether they would like to learn more about the scales after having participated in our study; and (iv) whether they would like to use these scales in their daily medical practice.

2.4 Prognostic scales included in the study A review of literature was performed via Medline and based on a recent review published in 2017.18 A large number of validated prognostic tools exist in the international literature. The choice of tools to include in this study was made based on the following criteria: (1) we retained any scale for which a validated French adaptation is available; and (2) among the seven main scales identified by a recent review of the literature, two were validated in only one study each and were therefore not retained for inclusion in this study (internal and external validity). Finally, five main prognostic scales were retained namely: PPS,11, 26-31 validated in patients with or without cancer followed up in palliative care, comprising six subjective criteria: physical performance (%) based on five observable parameters: the degree of ambulation, ability to do activities/extent of disease, ability to do self-care, food/fluid intake, and state of consciousness PaP score,12, 20, 32-35 validated in patients with solid tumors not eligible for specific treatment (except palliative radiotherapy and hormone therapy), a mixed scale comprising both biological and clinical items, covering six criteria: dyspnea, anorexia, Karnofsky Performance Status (KPS), Clinical Prediction of Survival (CPS), total white blood count (WBC), and lymphocyte percentage PPI,13, 36-42 validated in patients with cancer at the advanced palliative phase, comprising of five purely clinical criteria: Performance Status (PS), oral intake, edema, dyspnea at rest, and delirium. GPS,14, 22, 43, 44 validated in patients with cancer (operable or not, patients receiving chemotherapy and/or radiotherapy), comprising two biological criteria: albumin and C-reactive protein. The Barbot (or Pronopall) score,15, 45, 46 validated in patients with cancer at the advanced palliative phase with an estimated survival of <6 months but excluding patients with hematological malignancies. This is a mixed score comprising four criteria: PS, number of metastatic sites, serum albumin, and lactate dehydrogenase. 2.5 Evaluation of the validity of our study questionnaire

The questionnaire was designed jointly by one palliative care physician and one oncologist, both qualified in research methodology. In addition, a literature review was performed to inform the question design and the areas to investigate. A methodologist then reviewed the questionnaire to ensure that the data could be properly collected, extracted, and analyzed. Finally, the questionnaire was piloted on seven physicians (a mix of oncologists and palliative care physicians) to verify comprehension, fluidity, and time required for completion.

2.6 Ethical considerations

Since this study was considered as an evaluation of professional practices, and in accordance with French legislation, Ethics Committee approval was not required for this study. However, the study was registered with the relevant national authorities (National Institute for Healthcare Data, INDS, under the number MR3512280520). Participants were informed that their participation was voluntary, and together with the questionnaire, participants also received an information leaflet, and a form allowing them to withdraw their consent. The data were anonymous, and a pseudonymization code was used to enable back-identification of individual questionnaires via a personal code created by each participant at the end of the questionnaire.

2.7 Statistical analysis

Data were extracted from the online platform and analyses were performed using SPSS version 21.0 (IBM Inc). Quantitative data are presented as mean ± standard deviation (SD) or median [interquartile] and were compared using the Student t or Mann–Whitney U test as appropriate. Qualitative variables are presented as number (percentage) and were compared using the chi square or Fisher's exact test.

3 RESULTS

After the exclusion of incomplete questionnaires (88 partial answers among 413 respondents), the participation rate was 9.6% (325 responses from a total of 3408 contacted). The participation rate among palliative care physicians was higher compared to oncologists at 38% (175 responses out of 454 contacted), whereas only 4% of oncologists participated in the survey (119 responses out of 2954 contacted). A total of 294 complete responses were analyzed (Figure 1). The characteristics the respondents are detailed in Table 1.

Flow chart for the ONCOPRONO study, a national survey to assess the knowledge and use of prognostic scales by oncologists and palliative care physicians in adults with advanced cancer

TABLE 1. Demographic and professional characteristics of respondents from the ONCOPRONO study Demographical and professional characteristics of respondents

All

(N = 294)

Oncologists

(N = 119)

Palliative care physicians

(N = 175)

Age (years, SD) 43.8 (10.5) 41.8 (10.2) 44.7 (11.4) Sex Female 170 (57.8%) 62 (52.1%) 108 (61.7%) Male 124 (42.2%) 57 (47.9%) 67 (38.3%) Type of establishment Academic teaching hospital 80 (27.2%) 34 (28.6%) 46 (26.3%) Cancer center 54 (18.4%) 36 (30.2%) 18 (10.3%) Public (general, non-academic) hospital 112 (38.1%) 35 (29.4%) 77 (44.0%) Private hospital 48 (16.3%) 14 (11.8%) 34 (19.4%) Medical specialty Oncology (medical and radiotherapy) 80 (27.2%) 73 (61.3%) 7 (4.0%) Medical specialty except oncology 209 (71.1%) 44 (37.0%) 165 (94.3%) Family practice 159 (54.1%) 9 (7.6%) 150 (85.7%) Other medical specialty 50 (17.0%) 35 (29.4%) 15 (8.6%) Surgery 2 (0.7%) 2 (1.7%) 0 (0%) Experience ≤5 years 80 (27.2%) 30 (25.2%) 50 (28.6%) 6–10 years 82 (27.9%) 33 (27.7%) 49 (28%) 11–20 years 83 (28.2%) 34 (28.6%) 49 (28%) ≥20 years 49 (16.7%) 22 (18.5%) 27 (15.4%) Frequency of collaboration Never to rarely — 10 (7.7%) 9 (4.7%) Often to frequently — 120 (92.3%) 179 (95.3%)

Among the 294 participants, 10.2% (n = 30) were not aware of the existence of prognostic scales, and 53.4% (n = 157) reported limited knowledge (existence/name some criteria). Palliative care physicians were more knowledgeable about prognostic scales than oncologists (42.3% (n = 74) vs. 27.8% (n = 33) respectively, p = 0.015).

Overall, 27.2% of participants (n = 80) reported using the prognostic scales. There was no difference between palliative care physicians and oncologists in terms of use (30.3% (n = 53) vs. 22.7% (n = 27) respectively, p = 0.15). Table 2 presents how well each scale was known and how widely it was used by both groups of physicians. The Pronopall score was both the best known (65.4%, n = 70) and most widely used (60%, n = 48) followed by the PPS scale, both in terms of knowledge (51.4%, n = 55) and use (35%, n = 28). Both knowledge (68.9%, n = 51 vs. 12.1%, n = 4, p < 0.001) and use (52.8%, n = 28 vs. 0%, p < 0.001) of the PPS scale were greater among palliative care physicians than among oncologists, whereas there was no difference between the two specialities regarding the Pronopall score.

TABLE 2. The most widely known and used prognostic scales, as reported by respondents in the ONCOPRONO study Prognostic scales: most known and used

Those with good knowledge

(N = 107)

Oncologists with good knowledge

(N = 33)

Palliative care physicians with good knowledge

(N = 74)

p-value

All users

(N = 80)

Those using the scales and working in oncology

(N = 27)

Those using the scales and working in palliative care

(N = 53)

p-value Palliative Performance Scale (PPS)11 55 (51.4%) 4 (12.1%) 51 (68.9%) <0.001 28 (35%) 0 (0%) 28 (52.8%) <0.001 Palliative Prognostic Score (PaP)12 18 (16.8%) 2 6.1%) 16 (21.6%) 0.04 3 (3.7%) 0 (0%) 3 (5.7%) 0.52 Barbot score (Pronopall score)13 70 (65.4%) 21 (63.7%) 49 (66.2%) 0.79 48 (60%) 20 (74%) 28 (52.8%) 0.11 Palliative Prognostic Index (PPI)14 18 (16.8%) 1 (3.0%) 17 (23%) 0.01 4 (5%) 1 (3.7%) 3 (5.7%) 1.00 Glasgow Prognostic Score (GPS)15 12 (11.2%) 3 (9.1%) 9 (12.2%) 0.64 3 (3.7%) 1 (3.7%) 2 (3.8%) 1.00

The rate of use of the scales varied, with most respondents stating they used them between several times per month (38.75%, n = 31) and several times per week (28.75%, n = 23). The most common circumstances in which the scales were used are described in Table 3. Overall, the main reason for their use was with a view to limiting chemotherapy (n = 44, 55.7%). For oncologists, the scales were used primarily to limit chemotherapy (84.6%, n = 22), limit targeted therapies (42.3%, n = 11), and during discussions prior to admission to intensive care (30.8%, n = 8).

TABLE 3. The three most important situations for the use of prognostic scales, among self-reported scale users in the ONCOPRONO study The three most important situations for use of prognostic scales, among users

All users

(N = 79)

Users working in oncology

(N = 26)

Users working in palliative care

(N = 53)

p-value Oncologists Limitation of chemotherapy 44 (55.7%) 22 (84.6%) 22 (41.5%) <0.001 Limitation of targeted therapies including immunotherapy 14 (17.7%) 11 (42.3%) 3 (5.7%) <0.001 Discussion before going to the intensive care unit 22 (27.8%) 8 (30.8%) 14 (26.4%) 0.68 Palliative care physicians Limitation of invasive procedures (drain, gastrostomy, and palliative surgery) 31 (39.2%) 6 (23.1%) 25 (47.2%) 0.06 Limitation of artificial nutrition 30 (38%) 6 (23.1%) 24 (45.3%) 0.06 Drafting of care limitations/precisions regarding intensity of care 29 (36.7%) 6 (23.1%) 23 (43.4%) 0.07

Palliative care physicians reported using the scales to limit invasive treatment(s) (47.2%, n = 25), limit artificial nutrition (45.3%, n = 24), and for the physicians to decide on the limitations of care (43.4%, n = 23). There was a difference between the rate of use between oncologists and palliative care physicians in terms of limitation of chemotherapy and targeted therapy. In total, among the 79 physicians who reported using the scales, 98.75% thought that they were clinically relevant, with 52.5% (n = 42) stating that they sometimes found them helpful, 36.25% (n = 29) often, and 10% (n = 8) always.

The main obstacles to wider use of the prognostic scales as cited by the respondents are detailed in Table 4. The main barriers cited were a lack of training (54.2%, n = 116), the lack of a consensus regarding scale selection (28.5%, n = 61), and the lack of any need for such scores, because experience was stated to be more useful than using the scores (26.2%, n = 56).

TABLE 4. Obstacles to the use of prognostic scales cited by self-reported nonusers of the scales in the ONCOPRONO study Obstacles to use of prognostic scales

All non-users

(N = 214)

Non-users working in oncology

(N = 92)

Non-users working in palliative care

(N = 122)

p value Scales not recognized 46 (21.5%) 25 (27.2%) 21 (17.2%) Too long 18 (8.4%) 11 (11.9%) 7 (5.7%) Too many scales in oncology 37 (17.3%) 26 (28.3%) 11 (9.0%) <0.001 Too difficult to implement 11 (5.1%) 5 (5.4%) 6 (4.9%) Unreliable 11 (5.1%) 2 (2.2%) 9 (7.4%) Useless 56 (26.2%) 23 (25%) 33 (27.0%) 0.73 No consensus on which one to use 61 (28.5%) 28 (30.4%) 33 (27.0%) 0.58 Sometimes invasive (blood test) 14 (6.5%) 0 (0%) 14 (11.5%) No training in use of scales 116 (54.2%) 57 (62%) 59 (48.3%) 0.04 If palliative care practitioners do not use them, it would seem they are not useful 19 (8.9%) 14 (15.2%) 5 (4.1%)

Most respondents (96.3%, n = 283) searched for guidelines on supportive and palliative care one or several times per year (39.8%, n = 117), one or several times per month (47%, n = 138), or even one to several times per week (9.5%, n = 28). The preferred sources of information in France were national professional associations such as the French-language Society for Supportive and Palliative Care (AFSOS) (73.5%, n = 208), and the French Society for Palliative Care (SFAP) (70.7%, n = 200), followed by publications in the scientific literature (61.8%, n = 175), presentations at congresses (48.8%, n = 138) and international professional associations such as the European Society for Medical Oncology (ESMO) (24.7%, n = 70) and the American Society of Clinical Oncology (ASCO) (18.4%, n = 52).

The three most cited criteria used by the physicians to evaluate prognosis in their patients were general status (n = 249, 84.7%), findings on clinical examination (such as delirium, dyspnea, and edema) (n = 157, 53.4%) and clinical undernutrition (n = 114, 38.8%) (Table 5). Overall, 84.4% (n = 248) agreed that the evaluation of prognosis in this population was important, and 69.8% (n = 205) agreed that the prognostic scores were useful for assessing prognosis, while 85.4% (n = 251) expressed a desire to receive training in their use, and 70.4% (n = 207) reported that they would like to use the scales in practice.

TABLE 5. The three most important prognostic criteria for assessing patient prognosis as reported by respondents in the ONCOPRONO study Prognostic criteria to assess patient prognosis (the three most important)

All respondents

(N = 294)

Respondents working in oncology

(N = 119)

Respondents working in palliative care

(N = 175)

p-value Clinical undernutrition 114 (38.8%) 45 (37.8%) 69 (39.4%) 0.69 General status (Performance Status or Karnofsky Index) 249 (84.7%) 106 (89.1%) 143 (81.7%) 0.08 Clinical Prediction of Survival 70 (23.8%) 32 (26.9%) 38 (21.7%) 0.31 Patient age 9 (3.1%) 8 (6.7%) 1 (0.6%) 0.002 Patient psychology 17 (5.8%) 3 (2.5%) 14 (8.0%) 0.04 Response to previous chemotherapy 66 (22.4%) 43 (36.1%) 23 (13.1%) <0.001 Number of metastatic sites 26 (8.8%) 3 (2.5%) 23 (13.1%) <0.01 Location of primary cancer 18 (6.1%) 13 (10.9%) 5 (2.8%) <0.01 Patient comorbidities 75 (25.5%) 33 (27.7%) 42 (24.0%) 0.47 Social context 2 (0.7%) 1 (0.8%) 1 (0.6%) 1.00 Clinical criteria (including confusion, dyspnea, and edema) 157 (53.4%) 46 (38.6%) 111 (63.4%) <0.01 Biological criteria (including Albumin, CRP, and LDH) 64 (21.8%) 17 (14.3%) 47 (26.8%) <0.001 4 DISCUSSION

This is the first study to describe the state of knowledge and frequency of use of prognostic scales for the evaluation of expected survival in patients with advanced cancer among oncologists and palliative care physicians. A key finding of this study was that prognostic scales for assessing expected survival were still relatively poorly known among oncologists and palliative care physicians in France, with 63.6% of physicians indicating that they knew little about them, if anything at all.

The obstacles to the wider use of these scales are a need for training in their use/interpretation, and the lack of consensus about which scale to use. To address this need, physicians reported that they relied on national and international guidelines and other scientific publications in the international literature to further their knowledge. However, guidelines providing a consensus about the role of these scales in the discussions surrounding patient management are still lacking. Furthermore, the dissemination of knowledge in this specific field may be impeded by the fact that major therapeutic innovations generate greater interest and prognostic scales may not benefit from the same level of attention. Another explanation why these scales were not widely known could reside in the level of education provided in primary palliative care, which enables more recently graduated physicians in all disciplines to learn basic skills in palliative care, and ideally should prompt them to reflect in a more systematic way on the intensity and/or limitation of care for their patients. At present, the medical curriculum for future oncologists in France provides insufficient training in palliative care skills, with the result that many of them lack knowledge and experience.47-49

Another finding of this study was that the prognostic scales we asked about were not widely used, with only slightly more than a quarter of respondents (27.2%, (n = 80)) declaring that they used them. The low rate of use can naturally be a corollary of the fact that they were not widely known among our respondents, but may also be partially due to the constraints that their use involves. Indeed, such scales may be perceived as time-consuming, requiring time for completion, and constituting an additional tool to be applied on top of evaluations for pain, nutrition, anxiety, mental issues, and social context in patients whose management is already particularly long and complex. Furthermore, some physicians may simply not feel the need; indeed, there seemed to be a nonnegligible proportion of physicians who believed that their clinical judgement and experience was more helpful in estimating prognosis.

Among the participants who reported knowing and using the scales, the Pronopall and PPS scales were the most widely known and used, whereas the PaP, PPI, and Glasgow Prognostic Score were less commonly empl