To our knowledge, the present study was the first to provide real-world data about PC settings and the impact of this approach on survival of patients with advanced BTC.
In our study, 17% of the patients did not received active treatment, which is different from other studies (63% of iCCA received only PC in a study published by Neuzillet et al. in 2020(12), which included 3650 iCCA patients, not systematically with histological proof).
Histologically-proven CCA conduct to more specific treatment and most of the patients who do not have a biopsy are not accessible to active treatment. In the same way, more than a half (56%) of chemotherapy-treated patients had a second-line chemotherapy, which is more than other studies (less than one third (13)).
Our main objective was to analyse if early PC could improve OS. We found no evidence that OS was better in PC group compared to no PC group. It can be partially explained by the heterogeneity between groups. Indeed, groups were incomparable: patients who were addressed earlier, were suffering worse comorbidities and advanced diseases. It reveals that the group of patients who met PCT early after diagnosis has the worst survival due to several poor prognosis factors: high performans status (≥ 2 for 62% of them), more comorbidities (Charlson Index Score ≥ 2 for 47% of them), and only one third of them receive chemotherapy. Consequently, causes of death seem to be also different between groups. As explained before, patients from early PC groups are more fragile with more comorbidities and more advanced cancer. They died more from deterioration of general conditions (93% for early PC vs 59% no PC), and less of acute disease as sepsis (7% early PC vs 24% no PC) or gastro-intestinal bleeding (0% early PC vs 4% no PC). On the contrary, patients who did not receive PC died more from acute complication as sepsis or bleeding, with more hospitalizations in intensive care unit.
Differences are due to the retrospective character of our study, which shows our daily practice, with patients referred to PCT 0.9 to 1.3 months before death, generally when active treatments are no more possible. As a result, role of PC givers is limited, because we let them a very short period to act. They cannot build strong relationship with patient on important issues such as interruption of chemotherapy, end-of-life preferences, and meeting family members to have a global action. These results are similar to a French study showing median survival after first PCT intervention of 31 days(14). In the same study, 18% of the patients first met PCT 3 days before death.
In 2017, the American Society of Clinical Oncology (ASCO), published some recommendations about PC, stating that “patients with advanced cancer should receive dedicated PC services early in the disease course and concurrent with active treatment”(15). In our study, 56% of the patients have met at less once the PCT, which is similar that a retrospective study in pancreatic cancer patients (52%) (7). However, time-to-referral seems too late for impacting prognosis. Average time between diagnosis and PCR was 9.7 months, although median OS fluctuates from 3 to 16 months. Among 11% of the patients who met PCT, this meeting happened during the last hospitalization (a few days before death), which is extremely late.
The most frequently reasons for PCR in our study were asthenia (58%), “decision for becoming and place of care” (41%), pain (40%), psychological symptoms (12%) and then following the cessation of active therapeutics (11%) (which means that the oncologist stops taking care of the patient and a relay is made with PCT at the end of the active therapeutics).
To compare, Vinant et al. (14) showed in their study that the 3 major reasons for referral (for all cancer types) were pain (57%), early encounter (24%), decision for place of care (18%) and then in 6th position “decision to withhold or withdraw treatments” (9.3%). In our study, we saw that patients were mostly referred to PCT for difficulties for end-of-life management. Late PCR does not allow PCT to be a part of the decision about active treatment.
In our study, meeting PCT seemed to have a great impact on place of death (Table 3), because fewer patients died in conventional, emergency or intensive departments. In a retrospective study published in 2015, conducted in more than 500 000 cancer patients, proportion of death in PC units was 10% (16). Vinant et al. showed that this proportion raised to 30% when patients are referred to PCT (14). It reflects the positive impact of PC on the place of death, with less deaths in acute care units. Death in appropriate department is important for a better management of end-of-life. In palliative care units or home hospitalization, teams are familiar with these situations and they are able to anticipate future needs of patients, and to discuss of their preferences in order to head off difficult situations of end-of-life.
In a retrospective study in pancreatic cancer patients published in 2019, chemotherapy was prescribed during last month in 17% in case of early PCR and 25% in case of late PCR (non-significantly, p = 0,22) (9). 18% of our patients received chemotherapy within the last month of life (36% no PC, 10–30% with PC), which is similar to previous studies (18% received last-month chemotherapy in a study published in 2015 (16)). PC seems to reduce end-life chemotherapy. Finally, the use of chemotherapy during the last month is still a common situation. For patients, end-of-life chemotherapy does not seem beneficial, implying all adverse effects of drugs such as asthenia, nausea, infections leading to hospitalizations, without positive impact on prognosis. It could be avoided with early PCT meeting.
In the Australian study on pancreatic cancer patients (9), early PC allows a reduction of last-month visit ED when comparing early (24%) to late PC (42%) (p = 0,003). In our study, in the PC group, ED visit proportions varied from 7 to 20%, compared with 35% in the no PC group. Our data suggest that PC reduces ED visits during the last month of life. However, early PCR does not appear as a favourable factor contrary to previous studies. It could be explained by a lack of patients in the present work.
In 2005, Earl et al. proposed some objectives to evaluate aggressiveness in end-of-life care (6):
- Less than 10% of patients should receive chemotherapy in the last 14 days of life. In our study we collected last-month chemotherapy rate (36% without PC vs 10 to 30% with PC)
- Less than 4% of emergency room visits. In our study we had 35% no PC group and 7 to 20% PC group
- Less than 17% death in an acute care hospital. We had 8% death in ICU in non-PC group vs 0 to 5% in PC group. In conventional acute unit we had 73% in non PC group vs 21 to 25% in PC group.
- Less than 4% of admission in ICU. In our study this objective is achieved for the PC group (0–2%) but no for the no PC group (13%)