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Introduction

Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced oesophageal cancer1–4 and the benefit of oesophagectomy after nCRT has been questioned because a high pathological complete response rate is anticipated5. Active surveillance with frequent clinical, endoscopic, and imaging evaluation has been proposed as an alternative. The SANO trial6,7 is testing whether overall survival after active surveillance is non-inferior to that after standard oesophagectomy.

Active surveillance should preserve quality of life by avoiding surgical morbidity and the consequences of anatomicophysiological disruption8–10. However, regular diagnostic tests used for response evaluations are a physical and psychological burden11. A previous discrete-choice experiment12 in patients after nCRT (but before surgery) showed that overall survival, the likelihood of undergoing postponed surgery, and quality of life were factors influencing treatment preferences.

However, these attitudes may change after surgery, so these insights may help to better inform patients about the impact of the operation. The present study assessed patient preferences for active surveillance or standard surgery after patients had undergone oesophagectomy themselves.

Methods

A cohort study was undertaken in three high-volume centres. Patients were invited to participate in the present study if they presented at the outpatient clinic during follow-up of oesophageal or oesophagogastric junctional cancer. Patients were eligible if they had undergone nCRT according to the CROSS regimen followed by standard oesophagectomy at least 1 year previously. Treatment preferences were assessed and quantified by asking patients to state their preference over hypothetical alternatives in a questionnaire. An example of such a questionnaire is shown in Fig. S1. Treatment alternatives were described in terms of five attributes: 5-year survival, short-term and long-term health-related quality of life (HRQoL), annual number of diagnostic tests required, and the risk that postponed oesophagectomy would still be necessary. The importance of attributes and willingness to trade off survival for another attribute were assessed using a panel latent class model. A detailed description of the methods and more information on the discrete-choice experimental design are reported in Appendices S1 and S2.

Results

Patients

Between August 2018 and October 2020, 100 of 107 included patients (93.5 per cent) completed the questionnaire at a median of 16.4 (i.q.r. 12.4–24.5) months after surgery. Patient and tumour characteristics are shown in Tables S1 and S2, and HRQoL scores are summarized in Table S3.

Willingness of patients to consider treatment options

Some 28 of 100 patients chose active surveillance in all 18 choice sets. On the contrary, 28 of 100 patients chose standard oesophagectomy in all 18 choice sets. Table S4 shows the short- and long-term HRQoL of these groups. More patients in the group that chose active surveillance reported short-term pain or discomfort and worse long-term HRQoL than the group that chose oesophagectomy. Thirty-one patients also participated in an earlier discrete-choice experiment before oesophagectomy12 and the preferences are summarized in Table 1. The number of patients who preferred active surveillance remained stable before and after oesophagectomy.

Table 1
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Willingness of 31 patients to consider treatment options before oesophagectomy compared with with at least 1 year after oesophagectomy

Before oesophagectomyAfter oesophagectomy
Active surveillance (n = 11)Standard oesophagectomy (n = 8)Both treatment options (n = 12)
Active surveillance (n = 11)623
Standard oesophagectomy (n = 1)001
Both treatment options (n = 19)568
Before oesophagectomyAfter oesophagectomy
Active surveillance (n = 11)Standard oesophagectomy (n = 8)Both treatment options (n = 12)
Active surveillance (n = 11)623
Standard oesophagectomy (n = 1)001
Both treatment options (n = 19)568

Patients participated in a discrete-choice experiment before and after oesophagectomy.

Table 1
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Willingness of 31 patients to consider treatment options before oesophagectomy compared with with at least 1 year after oesophagectomy

Before oesophagectomyAfter oesophagectomy
Active surveillance (n = 11)Standard oesophagectomy (n = 8)Both treatment options (n = 12)
Active surveillance (n = 11)623
Standard oesophagectomy (n = 1)001
Both treatment options (n = 19)568
Before oesophagectomyAfter oesophagectomy
Active surveillance (n = 11)Standard oesophagectomy (n = 8)Both treatment options (n = 12)
Active surveillance (n = 11)623
Standard oesophagectomy (n = 1)001
Both treatment options (n = 19)568

Patients participated in a discrete-choice experiment before and after oesophagectomy.

Discrete-choice experiment

The three attributes that significantly influenced patients’ treatment preferences were 5-year survival, long-term HRQoL, and the risk of delayed oesophagectomy. The positive coefficients for 5-year survival indicated that patients (in all 3 classes) preferred a treatment that generates a positive effect on 5-year survival. A positive effect on long-term HRQoL also influenced preferences of patients belonging to the active surveillance class (β = 0.71, 95 per cent c.i. 0.36 to 1.06). A lower risk of delayed oesophagectomy significantly influenced treatment preferences of patients belonging to the ‘no clear preference’ class (β = −0.02, −0.04 to −0.01) (Table 2).

Table 2
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Patients’ preferences for active surveillance or standard oesophagectomy after neoadjuvant chemoradiotherapy and oesophagectomy

Treatment preference
Latent class 1
Importance scoreLatent class 2
Importance scoreLatent class 3
Importance score
Active surveillanceStandard oesophagectomyNo clear preference
Class probability0.3200.3580.322
Attribute levels, β value
 Alternative specific constant (standard oesophagectomy treatment)−2.48 (−3.39, −1.58)†15.49 (n.a.)1.78 (0.43, 3.13)†
 5-year overall survival (%)111
  45 (reference)
  601.15 (0.90, 1.41)†−27.37 (−97.63, 42.89)1.45 (0.77, 2.12)†
  751.98 (1.60, 2.35)†36.10 (n.a.)†4.57 (3.83, 5.31)†
 Short-term HRQoL*332
   A little bit better (reference)
   Much better−0.04 (−0.28, 0.21)3.21 (−195.07, 201.50)0.33 (−0.11, 0.78)
   A whole lot better0.18 (–0.20, 0.56)−6.18 (−164.82, 152.47)−0.09 (−0.66, 0.49)
 Long-term HRQoL223
   Current HRQoL (reference)
   A little bit better than current HRQoL0.09 (−0.16, 0.33)−1.28 (−199.57, 197.01)−0.09 (−0.57, 0.38)
   Much better than current HRQoL0.71 (0.36, 1.06)†14.85 (−104.13, 133.94)0.20 (−0.31, 0.71)
 Risk that postponed surgery is necessary−0.01 (−0.01, 0.00)5−0.38 (−8.31, 7.55)5−0.02 (−0.04, −0.01)†5
 Annual no. of diagnostic tests (per no.)−0.06 (−0.23, 0.11)4−6.39 (−46.06, 33.28)4−0.26 (−0.56, −0.04)4
Treatment preference
Latent class 1
Importance scoreLatent class 2
Importance scoreLatent class 3
Importance score
Active surveillanceStandard oesophagectomyNo clear preference
Class probability0.3200.3580.322
Attribute levels, β value
 Alternative specific constant (standard oesophagectomy treatment)−2.48 (−3.39, −1.58)†15.49 (n.a.)1.78 (0.43, 3.13)†
 5-year overall survival (%)111
  45 (reference)
  601.15 (0.90, 1.41)†−27.37 (−97.63, 42.89)1.45 (0.77, 2.12)†
  751.98 (1.60, 2.35)†36.10 (n.a.)†4.57 (3.83, 5.31)†
 Short-term HRQoL*332
   A little bit better (reference)
   Much better−0.04 (−0.28, 0.21)3.21 (−195.07, 201.50)0.33 (−0.11, 0.78)
   A whole lot better0.18 (–0.20, 0.56)−6.18 (−164.82, 152.47)−0.09 (−0.66, 0.49)
 Long-term HRQoL223
   Current HRQoL (reference)
   A little bit better than current HRQoL0.09 (−0.16, 0.33)−1.28 (−199.57, 197.01)−0.09 (−0.57, 0.38)
   Much better than current HRQoL0.71 (0.36, 1.06)†14.85 (−104.13, 133.94)0.20 (−0.31, 0.71)
 Risk that postponed surgery is necessary−0.01 (−0.01, 0.00)5−0.38 (−8.31, 7.55)5−0.02 (−0.04, −0.01)†5
 Annual no. of diagnostic tests (per no.)−0.06 (−0.23, 0.11)4−6.39 (−46.06, 33.28)4−0.26 (−0.56, −0.04)4

Values in parentheses are 95 per cent confidence intervals.

*

Compared with situation recalled 3 months after oesophagectomy. β, Class coefficient; n.a., not applicable; HRQoL, health-related quality of life.

Table 2
Open in new tab

Patients’ preferences for active surveillance or standard oesophagectomy after neoadjuvant chemoradiotherapy and oesophagectomy

Treatment preference
Latent class 1
Importance scoreLatent class 2
Importance scoreLatent class 3
Importance score
Active surveillanceStandard oesophagectomyNo clear preference
Class probability0.3200.3580.322
Attribute levels, β value
 Alternative specific constant (standard oesophagectomy treatment)−2.48 (−3.39, −1.58)†15.49 (n.a.)1.78 (0.43, 3.13)†
 5-year overall survival (%)111
  45 (reference)
  601.15 (0.90, 1.41)†−27.37 (−97.63, 42.89)1.45 (0.77, 2.12)†
  751.98 (1.60, 2.35)†36.10 (n.a.)†4.57 (3.83, 5.31)†
 Short-term HRQoL*332
   A little bit better (reference)
   Much better−0.04 (−0.28, 0.21)3.21 (−195.07, 201.50)0.33 (−0.11, 0.78)
   A whole lot better0.18 (–0.20, 0.56)−6.18 (−164.82, 152.47)−0.09 (−0.66, 0.49)
 Long-term HRQoL223
   Current HRQoL (reference)
   A little bit better than current HRQoL0.09 (−0.16, 0.33)−1.28 (−199.57, 197.01)−0.09 (−0.57, 0.38)
   Much better than current HRQoL0.71 (0.36, 1.06)†14.85 (−104.13, 133.94)0.20 (−0.31, 0.71)
 Risk that postponed surgery is necessary−0.01 (−0.01, 0.00)5−0.38 (−8.31, 7.55)5−0.02 (−0.04, −0.01)†5
 Annual no. of diagnostic tests (per no.)−0.06 (−0.23, 0.11)4−6.39 (−46.06, 33.28)4−0.26 (−0.56, −0.04)4
Treatment preference
Latent class 1
Importance scoreLatent class 2
Importance scoreLatent class 3
Importance score
Active surveillanceStandard oesophagectomyNo clear preference
Class probability0.3200.3580.322
Attribute levels, β value
 Alternative specific constant (standard oesophagectomy treatment)−2.48 (−3.39, −1.58)†15.49 (n.a.)1.78 (0.43, 3.13)†
 5-year overall survival (%)111
  45 (reference)
  601.15 (0.90, 1.41)†−27.37 (−97.63, 42.89)1.45 (0.77, 2.12)†
  751.98 (1.60, 2.35)†36.10 (n.a.)†4.57 (3.83, 5.31)†
 Short-term HRQoL*332
   A little bit better (reference)
   Much better−0.04 (−0.28, 0.21)3.21 (−195.07, 201.50)0.33 (−0.11, 0.78)
   A whole lot better0.18 (–0.20, 0.56)−6.18 (−164.82, 152.47)−0.09 (−0.66, 0.49)
 Long-term HRQoL223
   Current HRQoL (reference)
   A little bit better than current HRQoL0.09 (−0.16, 0.33)−1.28 (−199.57, 197.01)−0.09 (−0.57, 0.38)
   Much better than current HRQoL0.71 (0.36, 1.06)†14.85 (−104.13, 133.94)0.20 (−0.31, 0.71)
 Risk that postponed surgery is necessary−0.01 (−0.01, 0.00)5−0.38 (−8.31, 7.55)5−0.02 (−0.04, −0.01)†5
 Annual no. of diagnostic tests (per no.)−0.06 (−0.23, 0.11)4−6.39 (−46.06, 33.28)4−0.26 (−0.56, −0.04)4

Values in parentheses are 95 per cent confidence intervals.

*

Compared with situation recalled 3 months after oesophagectomy. β, Class coefficient; n.a., not applicable; HRQoL, health-related quality of life.

Willingness to trade off survival

Patients who had a preference for active surveillance were willing to trade off 5.4 (95 per cent c.i. 3.0 to 7.8) per cent 5-year survival to obtain long-term HRQoL that was much better than their current HRQoL.

Discussion

Patients tend to prefer the treatment they have undergone, even when randomized to a treatment (passive rather than active choice)13,14. After oesophagectomy, just over one in four patients would opt for active surveillance if they faced the choice again. Patients in the present study focused on long- rather than short-term outcomes in line with other studies12,15; this finding will facilitate interpretation of the SANO trial as long-term HRQoL is one of the study endpoints. These results should be awaited before active surveillance can be recommended as a standard of care.

Patients who preferred active surveillance in the present study were willing to trade off 5.4 per cent 5-year overall survival in order to obtain much better HRQoL. This seems modest compared with a previous discrete-choice experiment12 in which patients were willing to trade off 16 per cent 5-year survival when asked before surgery. If patients were asked to pick either active surveillance or standard oesophagectomy shortly before surgery, 1 of 31 patients would opt for standard oesophagectomy irrespective of the attribute levels. If the same question was asked of the same group of patients 1 year after oesophagectomy, 8 of 31 patients would opt for surgery. Perhaps the impact of oesophagectomy on HRQoL was not as negative as they expected. It may also reflect the selected group of study patients, who were disease-free at least 1 year after oesophagectomy. It is important to realize that preferences of patients and doctors do not always match15–17. All treatment options should be discussed with patients, even if this involves a treatment that does not offer the highest chance of cure.

One of the limitations of the present study is that the choice of a surgical or non-surgical treatment is more complex than the five attributes considered in this study. In addition, patients were asked to recall their HRQoL 3 months after surgery, which introduced a potential recall bias. Finally, no patients who underwent active surveillance were included and this information is relevant for optimizing shared decision-making.

Disclosure. The authors declare no conflict of interest.

Supplementary material

Supplementary material is available at BJS online.

This study was funded by the Dutch Cancer Society and Netherlands Organization for Health Research and Development.

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