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Metastatic spinal cord compression in prostate cancer: clinical and morphological studies
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Ryggmärgskompression vid metastaserande prostatacancer : kliniska och morfologiska studier (Swedish)
Abstract [en]

Background: Bone metastases occur in most patients with advanced hormone-refractory prostate cancer causing pain, pathologic fractures, and spinal cord compression. Few studies specifically address surgical treatment of metastatic spinal cord compression (MSCC) in prostate cancer. Criteria for identifying patients who may benefit from surgery are poorly defined. Most of the current knowledge regarding tumor biology in prostate cancer is based on studies of primary tumors or soft tissue metastases. The mechanisms regulating growth of bone metastases are not fully established.

Aims: a) to evaluate outcome after surgery for MSCC in prostate cancer and to identify prognostic factors for survival and functional recovery; b) to evaluate current practice for referral of prostate cancer patients with MSCC; c) to analyze expression of androgen receptor (AR), cell proliferation, apoptosis, and prostate-specific antigen (PSA) in bone metastases with regard to survival after surgery for complications of bone metastases.

Patients and Methods: We retrospectively evaluated the hospital records of 68 consecutive patients operated for metastatic spinal cord compression. Tumor tissue from bone metastases was obtained on spinal surgery (54 patients), fracture surgery (4 patients) and biopsy (2 patients), and analyzed by immunohistochemistry.

Results:

Study I: Mortality and complication rate after surgery was high. Patients with hormone-naïve disease and those with hormone-refractory disease with good performance status and without visceral metastases had more favorable survival. The ability to walk after surgery was related to better survival.

Study II: A new score for prognosis of survival after surgery for spinal cord compression includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The score is simple, tumor specific, and easy to apply in clinical practice.

Study III: Our results suggest that delays in diagnosis and treatment may have negative impact on functional outcome. Pretreatment ability to walk, hormone status of prostate cancer, and time from loss of ambulation influenced neurological recovery after surgery for spinal cord compression.

Study IV: High nuclear AR immunostaining in bone metastases and high preoperative serum PSA were associated with a poor outcome after metastasis surgery in patients with hormone-refractory prostate cancer. Short-term effect of castration therapy disclosed that nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected.

Conclusion:  Prostate cancer patients with metastatic spinal cord compression represent a heterogeneous group. We identified prognostic factors for survival and functional outcome, which may help clinicians in making decisions about treatment. Our results also implicate the need for development of local and regional guidelines for treatment of patients with spinal cord compression, as well as the importance of information to patients at risk.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2012. , 44 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1487
Keyword [en]
prostate cancer, bone metastasis, spinal cord compression, surgical treatment, survival prognosis, early diagnosis, androgen receptor
National Category
Orthopedics Cancer and Oncology
Research subject
Orthopaedics; Pathology; Oncology
Identifiers
URN: urn:nbn:se:umu:diva-54461ISBN: 978-91-7459-389-1 (print)OAI: oai:DiVA.org:umu-54461DiVA: diva2:523874
Public defence
2012-05-24, Sal B, Tandläkarhögskolan 9tr, Norrlands Universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-04-27 Created: 2012-04-26 Last updated: 2012-05-25Bibliographically approved
List of papers
1. Outcome after surgery for metastatic spinal cord compression in 54 patients with prostate cancer
Open this publication in new window or tab >>Outcome after surgery for metastatic spinal cord compression in 54 patients with prostate cancer
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2012 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 1, 80-86 p.Article in journal (Refereed) Published
Abstract [en]

Background and purpose The criteria for selecting patients who may benefit from surgery of spinal cord compression in metastatic prostate cancer are poorly defined. We therefore studied patients operated for metastatic spinal cord compression in order to evaluate outcome of surgery and to find predictors of survival. Patients and methods We reviewed the records of 54 consecutive patients with metastatic prostate cancer who were operated for spinal cord compression at Umeå University Hospital. The indication for surgery was neurological deficit due to spinal cord compression. 41 patients had hormone-refractory cancer and 13 patients had previously untreated, hormone-naïve prostate cancer. 29 patients were operated with posterior decompression only, and in 25 patients posterior decompression and stabilization was performed. Results Preoperatively, 6/54 of patients were able to walk. 1 month after surgery, 33 patients were walking, 15 were non-ambulatory, and 6 had died. Mortality rate was 11% at 1 month, 41% at 6 months, and 59% at 1 year. In the hormone-naïve group, 8/13 patients were still alive with a median postoperative follow-up of 26 months. In the hormone-refractory group, median survival was 5 months. Patients with hormone-refractory disease and Karnofsky performance status (KPS) of ≤ 60% had median survival of 2.5 months, whereas those with KPS of 70% and KPS of ≥ 80% had a median survival of 7 months and 18 months, respectively (p < 0.001). Visceral metastases were present in 12/41 patients with hormone-refractory tumor at the time of spinal surgery, and their median survival was 4 months-as compared to 10 months in patients without visceral metastases (p = 0.003). Complications within 30 days of surgery occurred in 19/54 patients. Interpretation Our results indicate that patients with hormone-naive disease, and those with hormone-refractory disease with good performance status and lacking visceral metastases, may be helped by surgery for metastatic spinal cord compression.

Place, publisher, year, edition, pages
Informa Healtcare, 2012
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-45327 (URN)10.3109/17453674.2011.590761 (DOI)21657974 (PubMedID)
Available from: 2011-07-04 Created: 2011-07-04 Last updated: 2017-12-11Bibliographically approved
2. Predicting survival for surgery of metastatic spinal cord compression in prostate cancer: a new score
Open this publication in new window or tab >>Predicting survival for surgery of metastatic spinal cord compression in prostate cancer: a new score
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2012 (English)In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 37, no 26, 2168-2176 p.Article in journal (Other academic) Published
Abstract [en]

Study design. We retrospectively analyzed prognostic factors for survival in prostate cancer patients operated for metastatic spinal cord compression.

Objective. The aim was to obtain a clinical score for prediction of survival after surgery.

Summary of background data. Survival prognosis is important when deciding about treatment of patients with metastatic spinal cord compression. The criteria for identifying prostate cancer patients who may benefit from surgical treatment are unclear.

Patients and methods The study comprised 68 consecutive patients with prostate cancer operated for metastatic spinal cord compression at Umeå University Hospital, Sweden. The indication for surgery was neurological deficit; 53 patients had hormone-refractory prostate cancer, and 15 patients had previously untreated, hormone-naïve prostate cancer. In 42 patients posterior decompression was performed and 26 patients were operated with posterior decompression and stabilization.

Results A new score for prediction of survival was developed based on the results of survival analyses. The score includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The total scores ranged from 0 to 6. Three prognostic groups were formulated: group A (n = 32) with scores 0-1; group B (n = 23) with scores 2-4, and group C (n = 12) with scores 5-6. The median overall survival was 3 (0.3 - 20) months in group A, 16 (1.8 - 59) months in group B, and in group C more than half (7 of 12) of patients were still alive.

Conclusion We present a new prognostic score for predicting survival of prostate cancer patients after surgery for metastatic spinal cord compression. The score is easy to apply in clinical practice and may be used as additional support when making decision about treatment.

Keyword
prostate cancer, bone metastasis, spinal cord compression, prognostic score
National Category
Orthopedics Cancer and Oncology
Research subject
Orthopaedics; Oncology
Identifiers
urn:nbn:se:umu:diva-54459 (URN)10.1097/BRS.0b013e31826011bc (DOI)
Note

Originally included in thesis in submitted form.

Available from: 2012-04-27 Created: 2012-04-26 Last updated: 2017-12-07Bibliographically approved
3. Early diagnosis and treatment is crucial for neurological recovery after surgery for metastatic spinal cord compression in prostate cancer
Open this publication in new window or tab >>Early diagnosis and treatment is crucial for neurological recovery after surgery for metastatic spinal cord compression in prostate cancer
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, 809-815 p.Article in journal (Refereed) Published
Abstract [en]

Background. Spinal cord compression is an oncological and surgical emergency. Delays in referral and diagnosis may influence functional outcome. It is therefore important to identify patients who will regain or maintain ability to walk after surgery. The aim of the present study was to examine current practice for referral and diagnosis of prostate cancer patients with spinal cord compression and to identify prognostic factors for neurological outcome after surgery.

Patients and methods. The study includes 68 consecutive patients with prostate cancer who underwent surgery due to neurological compromise.  Intervals from onset of neurological symptoms to referral, diagnosis, and treatment were analyzed in relation to functional outcome. The prognostic significance of preoperative clinical parameters on gait function one month after surgery was evaluated.

Results. Patients who were referred from local hospitals had longer delay to surgery than those who directly presented to the cancer centre (p=0.004). The rate of diagnosis with MRI increased through the week and peaked on Friday, with few patients being diagnosed during weekends. Ability to walk before surgery, hormone-naive prostate cancer, and/or shorter time from loss of ambulation were associated with more favorable neurological outcome. In patients with hormone-refractory disease who were unable to walk before surgery regaining of ambulation was associated with: duration of paresis <48 hours (p=0.005), good preoperative performance status (p=0.04), preoperative PSA serum level <200 ng/ml (p=0.03), and surgery with posterior decompression and stabilization (p=0.03).

Conclusion. Early diagnosis and rapid treatment of spinal cord compression in prostate cancer patients is crucial for neurological recovery. Rising of awareness for the condition among patients at risk and among physicians is mandatory as well as improvement of local and regional guidelines for treatment.

National Category
Orthopedics Cancer and Oncology
Research subject
Orthopaedics; Oncology
Identifiers
urn:nbn:se:umu:diva-54460 (URN)10.3109/0284186X.2012.705437 (DOI)
Available from: 2012-04-27 Created: 2012-04-26 Last updated: 2017-12-07Bibliographically approved
4. Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients
Open this publication in new window or tab >>Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients
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2010 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 17, no 4, 885-895 p.Article in journal (Refereed) Published
Abstract [en]

Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.

National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-36843 (URN)10.1677/ERC-10-0059 (DOI)000284490000009 ()20688881 (PubMedID)
Available from: 2010-10-12 Created: 2010-10-12 Last updated: 2017-12-12Bibliographically approved

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