Target and actual sample size of the patients to be evaluated are breast carcinoma (BC, 800/803), prostate carcinoma (PC, 550/549), lung carcinoma (LC, 400/414), and total (1750/1766). One hundred twenty clinics and 130 practices with a total of 268 physicians participated.
Clinical effect of osteoprotection (Table 2)
In the overall population, i.e., all observed indications, a positive correlation between osteoprotective therapy with bisphosphonates or denosumab and an improvement in bone-related complaints of patients can be observed after 3 months (p < 0.001) if osteoprotective therapy was started no later than 2 months after diagnosis of BM. However, the difference was only statistically significant in LC patients (p < 0.001, r = 0.291). A statistically significant difference in bone-related complaints before and after osteoprotective treatment was not observed for BC and PC patients (BC, p = 0.372; PC, p = 1). Differences in hormone sensitivity can be observed in PC, but these are not significant in hormone-sensitive PC (p = 1) or in castration-resistant PC (p = 0.813). The bone-related complaints were also recorded at the time of documentation (i.e., current therapy situation; at least 6 maximally 18 months after diagnosis of bone metastases). If osteoprotective therapy was continued until the time of documentation, this was associated with a significant improvement in symptoms, both in the overall population and in the individual indications (see Table 2). The effect strength is in the medium range for all indications.
Bone pain improvement was correlated with guideline adherence (“weak standard”) in lung cancer (p = 0.012) and breast cancer (p = 0.007) but not in prostate cancer (p = 0.758) (see Table 3). The pairwise comparisons in the indications LC and BC show different results with respect to major and minor deviations, which are however not significant at the adjusted α level but in part show a trend. While in LC differences are to be found between standard met and major deviation (r = 0.212, p = 0.060) and between major and minor deviation (r = 0.275, p = 0.055), there are no differences between standard met and minor deviations (r = 0.039, p = 1). In contrast, no difference can be found between major and minor deviations in BC (r = 0.034, p = 1), whereas slight differences with weak effect size are found between standard met and major (r = 0.091, p = 0.182) as well as minor deviation (r = 0.091, p = 0.168). A possible explanation for this could be that a large proportion of minor deviation in the LC indication is due to the use of a bisphosphonate not recommended or approved by the GL in this indication, which may nevertheless have similar efficacy. In BC, the number of patients not treated in compliance with GL (“weak standard”) is small (major dev. n = 34, minor dev. n = 28), so that the differences may be underestimated. There are clear differences in the indications investigated (see Figs. 1 and 2). The bisphosphonates being used outside of their labeled indications are presented in Figure 3 in the supplementary material.
Taking into account the accompanying medication (“strict standard”), the improvement of bone-related pain in all indications is associated with a GL-compliant therapy (Table 4). The Kruskal-Wallis test shows significant differences in all three indications: all indications (p < 0.001), LC (p = 0.006), BC (p = 0.006), and PC (p = 0.043). The pairwise comparisons show significant differences between standard met and major deviation for the entire spectrum (r = 0.137, p < 0.001) and BC (r = 0.109, p = 0.05) at low effect strength and differences between major and minor deviation for LC and mean effect strength (r = 0.230, p = 0.044).
Overall, in patients with improvement of bone pain, the percentage of patients with osteoprotective therapy was significantly higher, with (54%) and without (47%) additional systemic or radiotherapy than in patients with unchanged or worsening pain (see Figure 4A (supplementary material)). Similar effects are found in the three cancers analyzed (supplement Figure 4B–D).
Without taking the accompanying medication (calcium and vitamin D) into account, 61.6% of patients with lung cancer received osteoprotective treatment in accordance with the guidelines. Minor deviations were observed in 24.4% of patients; major deviations from GL recommendations were seen in 14.0% of patients. There is a significant difference between certified centers (OnkoZert, DGHO, or CCC; 69.1%) and non-certified centers (56.1%) (p < 0.001). However, certified centers recorded more major deviations (19.4% vs 10.0%) but significantly fewer minor deviations (11.4% vs 33.9%) than non-certified centers.
92.3% of BC patients were treated according to GL; in 4.2% of patients, there were minor deviations; and in 3.5% of patients, there were major deviations from the GL. A statistically significant difference between certified (92.1%) and non-certified centers (92.5%) was not observed (p = 0.086).
83.1% of PC patients were treated according to GL; in 11.8% of patients, there were minor deviations; and in 5.1% of patients, there were major deviations from GL-recommended treatment. There was no statistically significant difference between certified (80.2%) and non-certified centers (83.7%) (p = 0.285).
Substitution of calcium and vitamin D (strict standard)
If calcium and vitamin D are taken into account as concomitant medication (as major deviation), 15.0% of patients with lung cancer were treated according to GL, 4.8% had minor deviations, and 80.2% had major deviations.
42.0% of BC patients were treated in accordance with guidelines, 1.2% had minor deviations, and 56.8% had major deviations.
40.1% of PC patients were treated according to GL; in 4.2% of patients, there were minor deviations, and in 55.7% of patients, there were major deviations, (see Fig. 2).
Guideline adherence of participants (weak standard)
In patients treated in certified or comprehensive cancer centers (CERT), the guideline adherence was 85% vs 80% in other centers (p = 0.025). Guideline adherence differed between organ-specific oncologists and hematologist-oncologists (86% vs 76%, p < 0.001) and between hospital- and office-based physicians (78% vs 86%, p < 0.001).
Guideline adherence of participants (strict standard)
Taking the supplements of vitamin D and calcium into consideration, guideline adherence was 39% in CERT vs 32% in other centers (p = 0.013). Guideline adherence in organ-specific oncologists and hematologist-oncologists was 42% vs 22% (p < 0.001) and 34% vs 36% in hospital- and office-based physicians, respectively (p = 0.3).
When asked to assess their own GL adherence, 70.1% of physicians stated they adhered completely, and 24.6% said they adhered partially to GL.
Classification and Regression Tree (CART) analysis split treatment by gynecologists and urologists from general oncologists or lung cancer specialists (GOSL): guideline adherence was 48% vs 21.8%, p < 0.001. Gyneco- or urological oncologists were split attending ≤ 3 or more national congresses (guideline adherence 52.8% vs 24.3%, p < 0.001); guideline adherence in GOSL experienced in medical tumor therapy for ≤ 15 years or more was 43.4% vs 15.3%, p < 0.001. The latter group was split by attendance to no or ≥ 1 quality circles per year, 29.5% vs 9.4%, p = 0.001.