Approximately one quarter of patients with metastatic urothelial cancer present with bone metastases.1 Spinal bone metastases (SBM) are commonly associated with drug-resistant pain, pathological fractures and neurological complications, resulting in substantial morbidity and reduced quality of life (QoL).
Treatment of these patients requires an interdisciplinary approach and palliative radiotherapy (RT) remains the most important treatment option, particularly for persistent pain, existing or impending instability and neurological symptoms due to malignant spinal cord compression.2 The bone stability score introduced by Taneichi
All patients were treated with palliative RT for SBM from histologically diagnosed urothelial cancer at the Department of Radiation Oncology, University Hospital Heidelberg between January 2000 and January 2012. Patients’ data including survival status were collected from the institutional cancer registry. Patients received regular clinical follow-up examinations and computed tomography (CT) scans at 3 and 6 months after RT. All patients were included in the survival analyses.
Nineteen patients with osteolytic SBM of the thoracic or lumbar spine, and a minimum duration of follow-up to treatment of 6 months were included in the stability analyses. For each patient, the most severe metastasis according to the Taneichi
This study was conducted in accordance with the declaration of Helsinki and was approved by the independent ethics committee of the University of Heidelberg on 22 October 2012 (# S-513/2012). The requirement of informed consent was waived by the ethics committee, due to the retrospective nature of the study.
RT was performed for osseous instability in 18.5% (n = 7), for pain in 78.9% (n = 30), and for neurological symptoms in 2.6% (n = 1) of patients. Pain and neurological deficits as well as their alterations after RT were recorded during the follow-up examinations, in case they were linked to the irradiated area. Prior fractures affecting the vertebrae in the treated area were detected in the treatment planning CT scans in 10 patients (26.3%). In 1 patient (3%), a new fracture was found after RT. Nine patients (24%) also had distant metastases in other organs. Most patients were males (n = 30, 79%) and had a Karnofsky performance status (KPS) < 80% (n = 29; 76.3%). Fourteen patients (37%) had received chemotherapy (ChT) with cisplatin and gemcitabine prior to RT. Only 4 patients (10.5%) received concomitant bisphosphonates (Table 1).
Patients’ characteristics of all patients with urothelial cancer and spinal bone metastases
Patients’ characteristics
Median
70 years
Range
35-82 years
%
Female
8
21.0%
Male
30
79.0%
40-60%
12
31.6%
70%
17
44.7%
80%
9
23.7%
Urothelial carcinoma
38
100%
Thoracic
18
47.4%
Lumbar
20
52.6%
Single
15
39.5%
Multiple
23
60.5%
Overall
9
23.7%
Lungs
6
15.8%
Liver
5
13.2%
Brain
2
5.3%
Yes
6
15.8%
No
32
84.2%
Instability
7
18.4%
Neurological symptoms
1
2.6%
Pain
30
79.0%
10 x 3 Gy
24
63.2%
14 x 2.5 Gy
3
7.9%
20 x 2 Gy
11
28.9%
Chemotherapy
14
36.8%
Bisphosphonates
4
10.5%
RT planning was performed based on CT scans, and treatment was performed using a posterior photon field with an energy of 6 MV. The planning target volume (PTV) covered the affected vertebral body as well as those immediately above and below. The fractionation schedule was selected individually for each patient, depending on the patient’s general state of health, the current staging, response to current therapy and the respective prognosis. The most frequent fractionation schedule was 10 x 3 Gy (Table 1).
Survival was calculated with the Kaplan-Meier method and presented graphically. Patients, who were lost to follow-up, were censored for statistical analyses. Overall survival (OS) was defined as the time from initial diagnosis of urothelial cancer until death and “bone survival” (BS) as the time from first diagnosis of SBM until death. “Radiotherapy survival” (RTS) was defined as the time between start of RT and death. For the assessment of the distribution of Taneichi
The median follow up of all patients was 1.8 years (mean 2.4 years, range 0.3–8.6 years). All patients died during follow-up. OS after 6 months, 1 year and 2 years was 90%, 80% and 40%, respectively (Figure 3). BS was 85%, 64% and 23% after 6 months, 1 year and 2 years, respectively (Figure 4). RTS after 6 months, 1 year and 2 years was 42%, 18% and 5%, respectively (Figure 5).
Twenty of the 38 patients (52.6%) were classified as unstable before RT. One of the initially unstable metastases was classified as stable at 3 and 6 months after RT. Additionally, one patient with an initially stable metastasis showed progression of the osteolytic lesion with a new pathological fracture after RT and was classified as unstable after 3 and after 6 months. Overall, 10 of the 19 surviving patients (52.6%) were classified as unstable and nine (47.4%) were classified as stable after 3 and after 6 months. The evaluation of the distribution of Taneichi
Distribution of subtypes A to G of the Taneichi Score over the course of time (0–6 months)
Mean calculated metastasis size and mean bone density were 413.8 mm2 ± SD 253.6 and 110.8 HU ± SD 63.9 at initial assessment. At 3 months after RT, we observed a bone density of 125.7 HU ± SD 82.6 and after 6 months a bone density of 127.5 HU ± SD 85.6. The increase of bone density of 25.0 HU ± 49.7 SD after 3 months and 24.2 HU ± 52.2 SD after 6 months was statistically significant (p = 0.001; p = 0.037).
The documented indication for RT was pain in 30 patients and only 26.7% (n = 8) reported pain relief (≥ 2 points on the visual analogue scale). One patient (2.6%) had a neurological deficit with paresthesia of the right laterodorsal thoracic wall and this was unchanged 6 months after RT. None of the patients developed a new neurological deficit.
While survival was comparable to previously published data on patients with metastatic urothelial cancer11, we found RTS with 42% after 6 months to be particularly poor. We believe this to be attributable to patients’ extensive morbidity, with a KPS <80% in 76.3% and additional extra-osseous metastases in 9 out of 38 patients, at the initiation of RT, since earlier publications on different ChT regimens in patients with metastatic urothelial cancer reported visceral metastases as well as reduced performance status to be independent predictors of poor outcome. Moreover, these studies also described the presence of bone metastases to be an independent prognostic factor for survival.12,13 Nevertheless, there is only a minor impact of local therapy in these patients.
Generally, in patients with osseous metastases of the vertebral column, pain and instability are
major concerns regularly resulting in reduced QoL. Instability, especially when requiring a prescribed surgical corset, leads to reduced activity in daily life and further impairment of patients’ QoL. Taneichi
Benefit from sole palliative RT of painful or unstable SBM in patients with urothelial cancer is limited. Given the short survival and poor local response, patients should be carefully selected for palliative RT based on their KPS, and longer fractionation schedules, as used in our patients, should be avoided. However, concomitant bisphosphonates may improve outcome in terms of re-ossification, pain relief and survival.