2Department of Biomedical and Clinical Sciences University of Milan, "Luigi Sacco" Hospital, via G. B. Grassi 74, 20157 Milano, Italy
Suhasini Gazula, Super Specialist - Senior Scale & Head, Department of Paediatric Surgery, ESIC Super speciality Hospital,
Sanathnagar, Hyderabad, India, E-mail:
DOI: http://dx.doi.org/10.15226/2376-4570/3/1/00121
Methods: 253 consecutive breast cancer patients were reviewed: SLN was analyzed by OSNA in 114 cases and by standard histopathology in 139 cases. Nodal involvement detection, reintervention rate, time between surgery and adjuvant therapy were assessed. A cost analysis of OSNA vs. standard histopathology was performed.
Results: With OSNA the re-intervention rate significantly decreased (10.79% vs. 0%, p = 0.0003), and adjuvant therapy started earlier (38.5 days vs. 23.8 days, p < 0.0001). Total cost per patient was 5,990.8€ for histopathology vs. 4,308€ with OSNA (p < 0.0001) if positive SLN. In case of negative SLN costs were similar (2,419.6€ vs. 2,425.2€, p = 0.947).
Conclusions: OSNA reduces re-interventions, allows to start earlier adjuvant therapy and is more cost-effective than histopathology.
Keywords: Breast cancer; Sentinel lymph node biopsy; OSNA; Cost analysis
A cost analysis has been performed comparing OSNA and postoperative histopathological examination of SLN. For cost analysis the mean operative time (minutes) for the two groups of patients have been multiplied by the cost of 1 minute of surgery, according to the Cost Management Office of our Institute i.e. 6.8€ per minute, including staff, devices, drugs and sterilization costs. Lymphoscintigraphy costs, including the specific cost of the procedure, the cost of a dose of 99mTC, the cost of lymphoscintigraphy radiological reporting, and the cost of patients transport to the Department of Nuclear Medicine, have also been counted in the analysis. The total cost of lymphoscintigraphy was based on Lombardy Region rates registry for this procedure: 158€ per single procedure plus 40€ per patient for transport. Hospitalization costs have been calculated by multiplying the hospitalization days by the cost of 1 day of patient stay in the Surgery Department, according to the Cost Management Office of our Institute, i.e. 634€ per patient per day including costs of medical and non medical
|
Histopathology (HE plus IHC) |
OSNA examination |
Negative or ITC
|
Tumor cell deposits <0.2 mm |
<250 mRNA copies/uL |
Micrometastasis
|
Tumor cell deposits ≥0.2 mm and <2 mm |
250-5,000 mRNA copies/uL |
Macrometastasis
|
Tumor cell deposits ≥2 mm |
>5,000 mRNA copies/uL |
All these costs have been summed to obtain the total cost per patient, which was calculated for the four possible scenarios: positive SLN diagnosed on HE plus IHC, positive SLN analyzed with OSNA, negative SLN diagnosed on HE plus IHC, and negative SLN analyzed with OSNA. Total costs have been compared between the two techniques in case of positive and negative SLN.
Characteristic |
Histopathology (n=139) |
OSNA (n=114) |
p value |
Tumor size |
|||
pTis |
33 (23.74%) |
24 (21.05%) |
0.825 |
pT1 |
88 (63.31%) |
77 (67.54%) |
|
pT2 |
15 (10.79%) |
12 (10.53%) |
|
pTx |
3 (2.16%) |
1 (0.88%) |
|
Histological grade |
|
|
|
G1 |
39 (28.06%) |
37 (32.46%) |
0.646 |
G2 |
65 (46.76%) |
47 (41.23%) |
|
G3 |
35 (25.18%) |
30 (26.31%) |
|
Tumor type |
|||
Invasive ductal |
96 (69.06%) |
84 (73.68%) |
0.759 |
Invasive lobular |
7 (5.04%) |
5 (4.39%) |
|
DCIS |
36 (25.90%) |
36 (25.90%) |
|
Estrogen receptors |
|||
Negative |
17 (12.23%) |
18 (15.79%) |
0.466 |
Positive |
122 (87.77%) |
122 (87.77%) |
|
Progesterone receptors |
|||
Negative |
42 (30.22%) |
35 (30.70%) |
1.000 |
Positive |
97 (69.78%) |
79 (69.30%) |
|
Ki67 |
|||
≤14% |
68 (48.92%) |
61 (53.51%) |
0.528 |
>14% |
71 (51.08%) |
53 (46.49%) |
|
Her2/neu status |
|||
Positive |
13 (9.35%) |
15 (13.16%) |
0.421 |
Negative |
126 (90.65%) |
99 (86.84%) |
|
Sentinel node status |
|||
Micrometastasis |
6 (5.27%) |
6 (5.27%) |
0.105 |
Macrometastasis |
15 (10.79%) |
20 (17.54%) |
|
Negative/ITC |
20 (17.54%) |
88 (77.19%) |
|
Mean age of diagnosis, year (range) |
62 (38-82) |
62 (38-82) |
1.000 |
|
Histopathology |
OSNA |
p value |
Second surgery for axillary dissection n, (%) |
15 (10.79%) |
0 (0%) |
0.0003 |
Time between surgery and adjuvant therapy (days) |
38.5 (±16.1) |
23.8 (±7.7) |
<0.0001 |
Hospitalization costs in case of negative SLN resulted to be 1,458.2€ (±697.4€) for HE and 1,394.8€ (±443.8€) for OSNA, p=0.442; in case of positive SLN, these costs were 4,628.2€ (±896.6€) for HE and 2,979.8€ (±1,014.4€) for OSNA, p < 0.0001. Total cost per patient, including surgery, hospitalization and fixed costs for lymphoscintigraphy and patient transport have been determined for each group and subsequently for each SLN status. In case of positive SLN total cost per patient was 5,990.8€ (±916.1€) for HE plus IHC vs. 4,308€ (±1,037.2€) with OSNA (p < 0.0001); in case of negative SLN it was 2,419.6€ (±709.5€) for HE plus IHC vs. 2,425.2€ (±460€) with OSNA, p=0.947. All these data are reported in Table 4.
|
Histopathology (n = 139)
|
OSNA (n = 114) |
||||||
|
LNS+ (n=15) |
Costs |
LNS- (n=124) |
Costs |
LNS+ (n=20) |
Costs |
LNS- (n=94) |
Costs |
Mean operative time (first surgery) – 6.8€ per min |
53.2 (±19.5)
|
361.8€ (±132.6€) |
63 (±19.2) |
428.4€ (±130.6€) |
111.5 (±31.8) |
758.2€ (±216.2€) |
67.7 (±17.8)
|
460.4€ (±121€) |
Mean hospitalization stay (first surgery) – 634€ per day |
2.4 (±1) |
1,521.6€ (±634€) |
2.3 (±1.1) |
1,458.2€ (±697.4€) |
4.7 (±1.6) |
2,979.8€ (±1,014.4€) |
2.2 (±0.7) |
1,394.8€ (±443.8€) |
Mean operative time (second surgery) – 6.8€ per min |
68.8 (±19.6)
|
467.8€ (±133.3€) |
- |
- |
- |
- |
- |
- |
Mean hospitalization stay (second surgery) – 634€ per day |
4.9 (±1) |
3,106.6€ (±634€) |
- |
- |
- |
- |
- |
- |
Total cost per patient* |
5,990.8€ (±916.1€)** |
2,419.6€ (±709.5€) |
4,308€ (±1037.2€)** |
2,425.2€ (±460€) |
In our series OSNA has demonstrated to be an accurate and standard technique for sentinel node assessment, as previously reported in several validation studies [8, 23-26]. Moreover, the use of OSNA has reduced our second surgery rate for axillary dissection from 10.79% to 0% (p = 0.0003) thanks to its high intraoperative accuracy, thus demonstrating a role of OSNA in reducing second hospitalizations, with subsequent reduced patients discomfort. Klingler, et al. [16] have shown a similar reduction in the re-intervention rate for axillary dissection by using OSNA intraoperatively (9% vs. 39% if OSNA was not performed, p < 0.01). Furthermore, this rapid decision-making on the axilla allows a prompt starting of adjuvant therapy, with significant reduction in time between surgery and adjuvant treatment in patients with an involved SLN (23.8 days in case of intraoperative OSNA vs. 38.5 days with postoperative histopathology, p < 0.0001).
A less investigated feature of OSNA is cost-effectiveness, which is a matter of debate since OSNA is more expensive than morphological examination of the SLN [27]. A comprehensive cost-analysis of OSNA should include three levels of assessment: surgery costs, hospitalization costs, and pathological examination costs [27]. Surgery costs mainly vary as a function of the operative times, and in our series mean time of surgery was rather higher when including OSNA intraoperative assay (67.7 vs. 63 minutes without intraoperative assessment in case of negative SLN, p = 0.066). However, as expected, the two mean times were not significantly different, because in our centre the SLN biopsy is performed before the lumpectomy, and thus the waiting time of OSNA is spent in excision of the tumor without further elongation of surgery. For positive SLN patients mean operative times between the two groups were not different (122 vs. 111.5 min in HE and OSNA groups, respectively, p = 0.314), because the longer time required by OSNA is balanced by the longer time required for a new surgical access to the axilla in case of a second surgery. Considering only operative times and specific examination costs, OSNA is therefore more expensive in case of negative SLN (832.4€ vs. 763.4€, p < 0.0001), but on the other hand it is comparable to histopathology in case of positive SLN (758.2€€ vs. 829.6€, p = 0.315). As expected, mean hospitalization time was similar in the two groups in case of negative SLN (2.3 vs. 2.2 days), but increased significantly in histopathology group in case of positive SLN due to the need of readmission (7.3 vs. 4.7 days, p < 0.0001). As a consequence, hospitalization costs in case of negative SLN resulted to be similar between the two groups (1,458.2€ vs. 1,394.8€), but in case of the need of axillary dissection these costs markedly rise for HE group (4,628.2€ vs. 2,979.8€, p < 0.0001).
Considering surgery, hospitalization, pathology examination and fixed costs together, it was evident that OSNA is globally cost-effective compared to post-operative histopathology, since total costs were identical between the two groups of patients in case of negative SLN (2,419.6€ vs. 2,425.2€, p = 0.947), and strongly favourable for OSNA in case of positive SLN (4,308€ vs. 5,990.8€, p < 0.0001). These data suggest that, in case of a second hospitalization for further axillary surgery, global costs are not sustainable, and from this point of view OSNA becomes even more appealing.
Similar results have been reported in a recent cost-benefit French study in which the SLN has been analyzed by OSNA or by conventional post-operative histopathology [27]. The average pathology examination cost was markedly higher for OSNA (291.84€ vs. 35.04€); however, since the hospital stay was much longer in histopathology group due to re-hospitalization for axillary surgery (5.4 vs. 4.2 days), total cost of OSNA was lower compared to histopathology [27]. Notably, the reported costs for histopathology examination (35.04€) were much lower than that obtained in our study, but the Authors have not included staff costs. Interestingly, a significant cost difference between the two techniques was evident considering separately patients with or without axillary dissection, which was a common finding also in our study. Another relevant cost-benefit analysis by the Spanish group of Guillén-Paredes [28] has pointed out a reduction in total hospital stay with OSNA, saving up to 199.69€ per patient for hospitalization costs. Finally, a more complex analysis has been provided in a British study based on three different cost-analysis pathways: lumpectomy with axillary dissection, lumpectomy with SLN biopsy and postoperative histopathology, and lumpectomy with molecular analysis of the SLN [5]. Although this study demonstrated a substantial cost-effectiveness of molecular analysis compared to standard histopathology, it also highlighted that in some countries the avoidance of a second surgery with subsequent loss of reimbursement from National Health Services could discourage the adoption of intraoperative SLN examinations [5].
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