Review for 10.1186/s12876-023-02898-x (2023)

Title: An Age-group Analysis on the Efficacy of Chemotherapy in Older Adult Patients with
Metastatic Biliary Tract Cancer: A Japanese Cancer Registry Cohort Study
Version: 2 Date: 27 Apr 2023
Reviewer's report:
This is a retrospective propensity score matched study that sought to determine the efficacy of
chemotherapy versus best supportive care in a large cohort of elderly patients diagnosed with
metastatic biliary tract cancer(BTC). Clinically, deciding whether or not to offer chemotherapy
to older patients is a huge challenge, and this study may help clinicians who can't avoid the
question. However, there are a few things to consider.
Major point
1. In general, survival prolongation is an important goal of palliative chemotherapy in metastatic
solid tumors, and so is the purpose of the authors' study. Furthermore, given the nature of
BTC, which is predominantly diagnosed in older patients, the authors' intention to determine the
effectiveness of chemotherapy in older patients by analyzing overall survival seems reasonable.
However, in reality, the main reason for hesitancy to use chemotherapy in elderly patients is
probably not the lack of expectation of prolonged survival, but rather the fear of side effects
or decreased quality of life due to chemotherapy. In addition, it is necessary to consider the
clinical implications of extending survival to less than 5 months in elderly patients compared
to supportive care, even if the difference is statistically significant. Although different studies
report different results due to the heterogeneous nature of biliary tract cancer, which inevitably
includes a heterogeneous patient population, the overall survival of gemcitabine alone or
gemcitabine plus cisplatin in existing studies is generally reported to be around 6 to 8 months.
Therefore, it is hoped that the results of this study will provide additional justification for
recommending palliative chemotherapy in elderly patients. Especially in elderly patients,
even if palliative chemotherapy can prolong survival by about 5 months, it is difficult to
recommend chemotherapy to elderly patients in reality if quality of life is reduced, unexpected
chemotherapy-related adverse events, and unexpected admissions are frequent. I would suggest
that the authors analyze variables other than survival, such as toxicity, quality of life changes,
and pain before and after chemotherapy, to provide additional evidence that chemotherapy is
superior to best supportive care in elderly BTC patients.
2. It is a study of elderly patients with comorbidities, and the authors tried to reduce selection
bias through propensity score matched analysis, but because it is basically a retrospective study,
so the patients who were able to receive chemotherapy were patients with relatively good Barthel
index scores, and propensity matching was done for them, so only elderly patients with good
performance were included in both groups. And one of the drawbacks of propensity score
matching is that if the conditional independence assumptions are made incorrectly, it can lead to
inaccurate estimates and even increased bias in the results. Please clarify this as a limitation of
the study and it is suggested that the conclusion should state that chemotherapy may achieve an
overall survival gain of approximately five months compared to best supportive care in elderly
patients with good performance, rather than all elderly patients.
Minor point
1. May I inquire if you have data on the frequency of dose reduction in elderly patients? It is
anticipated that this rate may be higher among this population. If available, would it be possible
to assess the impact of dose reduction on overall survival?