Denosumab for the prevention of symptomatic skeletal events in patients with castration-resistant advanced prostate cancer: A comparison with skeletal-related events.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 35-35 ◽  
Author(s):  
Matthew R. Smith ◽  
Robert E. Coleman ◽  
Laurence Klotz ◽  
Kenneth B. Pittman ◽  
Piotr Milecki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Controlled Trial ◽  
Cord Compression ◽  
Castration Resistant ◽  
Pathologic Fractures ◽  
Skeletal Related Events ◽  
Fracture Surgery

35 Background: In a randomized controlled trial of men with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid (ZA) for reducing skeletal-related events (SRE, defined as pathological fracture, surgery or radiation to bone [including the use of radioisotopes], or spinal cord compression) (Fizazi, et al. Lancet 2011;377:813-822.). Recently, the composite endpoint of symptomatic skeletal event (SSE, defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression) was introduced as an alternative term/clinical trial endpoint to describe skeletal morbidity. Methods: Men with CRPC, ≥ 1 bone metastasis, and no prior IV bisphosphonate use received either SC denosumab 120 mg or IV ZA 4 mg (adjusted for creatinine clearance) in a blinded fashion every 4 weeks. Oral calcium and vitamin D supplements were recommended. SSEs included pathologic fractures considered symptomatic by the investigator, spinal cord compression and surgery and radiation to bone. Results: As previously reported, fewer men who received denosumab than ZA had confirmed first SREs, and experienced multiple SREs (Table). Similarly, fewer patients in the denosumab group than the ZA group had confirmed first SSE and multiple SSEs. The median (95% CI) estimate of time to first SSE (superiority analysis) for denosumab was not reached (28.8 mo, not estimable), and for ZA it was 24.2 (20.7, 30.2) mo (HR = 0.78 (0.66, 0.93) P = 0.01). Conclusions: Denosumab reduced the risk of skeletal events in men with CRPC regardless of endpoint definition as SRE or SSE. The risk of developing SSEs was reduced by up to 22% when comparing denosumab with ZA. Clinical trial information: NCT00321620. [Table: see text]

Impact of skeletal-related events on survival in patients with prostate cancer metastatic to bones.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 223-223
Author(s):  
Jean A. McDougall ◽  
Bernardo Haddock Lobo Goulart ◽  
Sean D Sullivan ◽  
Jeannine S. McCune ◽  
Aasthaa Bansal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Metastatic Prostate Cancer ◽  
Pathological Fracture ◽  
Cord Compression ◽  
Time Dependent ◽  
Risk Of Death ◽  
Skeletal Related Events ◽  
The Impact

223 Background: Skeletal related events (SREs), defined as pathological fracture, spinal cord compression, surgery or radiotherapy to the bone, occur in nearly half of men diagnosed with metastatic prostate cancer. Accurate assessment of the risk of death associated with SREs is important to making decisions about the use of recently approved treatments, which have been shown to decrease the frequency of skeletal events, yet estimating the impact of SREs on survival presents several methodological challenges given the recurrent time-dependent nature of exposure. Methods: A cohort of men >65years of age, diagnosed with prostate cancer and bone metastasis between January 1, 2004 and December 31, 2009 was identified from the Surveillance Epidemiology and End Results (SEER) registries were linked to Medicare Parts A and B claims. The outcome of interest, death from any cause, was ascertained from SEER and survival time was calculated from the date of metastatic prostate cancer diagnosis. Multivariable Cox proportional hazards models treating the occurrence of an SRE as a time-dependent exposure were used to estimate the hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the association between SRE occurrence, number, and type, and death. Results: Among 3,297 men with metastatic prostate cancer, 40% experienced ≥1 SRE during the observational follow-up period (median 19 months). Compared to men who remained SRE-free, cohort members who had ≥1 SREs had a two-fold higher risk of death (HR 2.2, 95% CI 2.0-2.4). Those whose first SRE was a pathological fracture had a 2.7-fold higher risk of death (HR 2.7, 95% CI 2.3-3.1), followed by spinal cord compression (HR 2.1, 95% CI 1.8-2.5), surgery (HR 1.8, 95% CI 1.5-2.2) and radiotherapy (HR 2.2, 95% CI 1.9-2.4). Compared to those experiencing only one SRE, men who experienced a second SRE of any type had double the risk of death (HR 2.2, 95% CI 1.9-2.6). Conclusions: SREs were associated with ≥50% reduction in overall survival. This finding is consistent across different types of SREs and supports using therapies to prevent or treat SREs in patients with prostate cancer metastatic to the bones.

scholarly journals Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 546
Author(s):  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
Angela Dalia Ricci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cord Compression ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Phase Iii Trials ◽  
Skeletal Related Events

Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)—such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab—are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.

scholarly journals Clinical outcome of surgical management for symptomatic metastatic spinal cord compression form prostate cancer.

2020 ◽  
Author(s):  
Yasuhide Miyoshi ◽  
Takashi Kawahara ◽  
Masahiro Yao ◽  
Hiroji Uemura
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Clinical Outcome ◽  
Spinal Cord Compression ◽  
Specific Antigen ◽  
Oncological Outcome ◽  
Cord Compression ◽  
Metastatic Spinal Cord Compression ◽  
Reconstruction Surgery ◽  
Castration Resistant

Abstract Background Metastatic spinal cord compression (MSCC) from prostate cancer (PC) influences not only patients’ prognosis but also their quality of life. However, little is known about the clinical outcome of surgery for MSCC from PC. We evaluated both the oncological and functional outcomes of decompression and reconstruction surgery for patients with symptomatic MSCC from PC. Methods We assessed 19 patients who underwent decompression and reconstruction surgery for symptomatic MSCC from PC. Of these 19 patients, 8 had metastatic hormone-naïve PC (mHNPC) and 11 had metastatic castration-resistant PC (mCRPC). Results The median age of the patients with mHNPC and mCRPC was 72 and 65 years, respectively. The median prostate-specific antigen level at the time of diagnosis of MSCC in patients with mHNPC and mCRPC was 910 and 67 ng/mL, respectively. Although two of eight patients (25.0%) with mHNPC were ambulatory preoperatively, six patients (75.0%) were ambulatory postoperatively. Among 11 patients with mCRPC, only 3 (27.3%) were ambulatory preoperatively, while 6 (54.5%) were ambulatory postoperatively. The median postoperative overall survival among patients with mHNPC and mCRPC were not reached and 8 months, respectively. Conclusions Decompression and reconstruction surgery for symptomatic MSCC from PC might contribute to a favorable functional outcome among men with mHNPC and mCRPC. However, its role in improving the oncological outcome remains unclear. The treatment strategy should be chosen by shared decision-making among patients, urologists, radiation oncologists, and orthopedic surgeons.

scholarly journals Clinical outcome of surgical management for symptomatic metastatic spinal cord compression form prostate cancer.

2020 ◽  
Author(s):  
Yasuhide Miyoshi ◽  
Takashi Kawahara ◽  
Masahiro Yao ◽  
Hiroji Uemura
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Clinical Outcome ◽  
Spinal Cord Compression ◽  
Specific Antigen ◽  
Oncological Outcome ◽  
Cord Compression ◽  
Metastatic Spinal Cord Compression ◽  
Reconstruction Surgery ◽  
Castration Resistant

Abstract Background Metastatic spinal cord compression (MSCC) from prostate cancer (PC) influences not only patients’ prognosis but also their quality of life. However, little is known about the clinical outcome of surgery for MSCC from PC. We evaluated both the oncological and functional outcomes of decompression and reconstruction surgery for patients with symptomatic MSCC from PC. Methods We assessed 19 patients who underwent decompression and reconstruction surgery for symptomatic MSCC from PC. Of these 19 patients, 8 had metastatic hormone-naïve PC (mHNPC) and 11 had metastatic castration-resistant PC (mCRPC). Results The median age of the patients with mHNPC and mCRPC was 72 and 65 years, respectively. The median prostate-specific antigen level at the time of diagnosis of MSCC in patients with mHNPC and mCRPC was 910 and 67 ng/mL, respectively. Although two of eight patients (25.0%) with mHNPC were ambulatory preoperatively, six patients (75.0%) were ambulatory postoperatively. Among 11 patients with mCRPC, only 3 (27.3%) were ambulatory preoperatively, while 6 (54.5%) were ambulatory postoperatively. The median postoperative overall survival among patients with mHNPC and mCRPC were not reached and 8 months, respectively. Conclusions Decompression and reconstruction surgery for symptomatic MSCC from PC might contribute to a favorable functional outcome among men with mHNPC and mCRPC. However, its role in improving the oncological outcome remains unclear. The treatment strategy should be chosen by shared decision-making among patients, urologists, radiation oncologists, and orthopedic surgeons.

Prognostic implication of gait function following treatment for spinal cord compression in men diagnosed with prostate cancer

2019 ◽  
Vol 53 (4) ◽  
pp. 222-228 ◽  
Author(s):  
Caroline Sophie Lehrmann-Lerche ◽  
Frederik Birkebæk Thomsen ◽  
Martin Andreas Røder ◽  
Morten Hiul Suppli ◽  
Klaus Brasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Prognostic Implication ◽  
Gait Function

Comparison of two Different Radiotherapy Schedules for Spinal Cord Compression in Prostate Cancer

1998 ◽  
Vol 84 (4) ◽  
pp. 472-477 ◽  
Author(s):  
Ernesto Maranzano ◽  
Paolo Latini ◽  
Sara Beneventi ◽  
Luigi Marafioti ◽  
Fabrizio Piro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Response Rate ◽  
Recovery Of Function ◽  
Performance Status ◽  
Cord Compression ◽  
Severe Toxicity ◽  
Indwelling Catheter ◽  
Short Course

Aims and background To assess the clinical outcome and toxicity of two different radiotherapy (RT) schedules for the management of metastatic spinal cord compression from prostate cancer, we performed a prospective analysis of 44 patients with the complication. Methods Two different RT schedules were adopted, a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5, and a short-course regimen of 8 Gy, 7 days rest, and then 8 Gy. The split-course RT was adopted for all prostate cancer patients referred to our center between 1986 and 1992. Starting in 1993, the short-course RT was added for patients with a poor prognosis (i.e., paresis or paraplegia, low performance status, and/or short life expectation), whereas others still underwent the split-course regimen. So, 27 (61%) patients were treated with the split-course and the other 17 (39%) with the short-course regimen. Medium follow-up was 48 months (range, 6 to 123). Results Back pain total response rate was 82%. Effectiveness of RT on motor and bladder capacity was conditioned by pretreatment status of patients. All 20 (100%) walking cases maintained the function, whereas 11 of 24 (46%) with motor impairment regained the ability. The difference in response rate was statistically significant (P<0.001). All 36 (100%) patients, able to void at presentation preserved the capacity, whereas 3 of 8 (38%) with sphincter dysfunction no longer needed an indwelling catheter. Posttreatment neurologic status was the only factor found to affect survival. Median survival, 9 months for the whole group, was 10 and 2 months for posttreatment walking and nonwalking patients, respectively (10 vs 2 months, P<0.001). Neither presence of other metastases nor RT regimen used (split vs short-course) conditioned response rate, duration of response or survival. Acute or late, severe toxicity was never recorded. No patient complained of spinal cord morbidity. Conclusions Both split-course and short-course RT schedules were effective and without complications. Early diagnosis was the most important prognostic factor, but there was also recovery of function in about half of the patients unable to walk, and about one-third of patients with bladder dysfunction before treatment. Since length of the course of therapy is a factor with an important impact on the patient's quality of life, the short-course RT regimen adopted in the trial merits further investigation.

Spinal Cord Compression Due to Anaerobic Vertebral Osteomyelitis in a Patient with Metastatic Prostate Cancer

1995 ◽  
Vol 21 (2) ◽  
pp. 457-458 ◽  
Author(s):  
S. Bilgrami ◽  
E. L. Pesanti ◽  
N. T. Singh ◽  
R. J. Cobb ◽  
L. L. Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Metastatic Prostate Cancer ◽  
Vertebral Osteomyelitis ◽  
Cord Compression

Skeletal related events (SREs) in metastatic androgen independent prostate cancer (AIPC) treated with docetaxel-based chemotherapy: Results from ASCENT

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4614-4614 ◽  
Author(s):  
J. S. Chan ◽  
C. W. Ryan ◽  
P. M. Venner ◽  
D. P. Petrylak ◽  
G. S. Chatta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Cord Compression ◽  
Entire Group ◽  
Large Prospective Study ◽  
Free Survival ◽  
Skeletal Related Events ◽  
The Impact ◽  
Androgen Independent

4614 Background: Docetaxel prolongs survival in AIPC patients and zoledronic acid (ZA) reduces the incidence of SREs. The SRE incidence of patients treated with docetaxel-based chemotherapy has not previously been reported. Methods: ASCENT was a randomized clinical trial that compared weekly DN-101 (calcitriol, 45 μg p.o. on day 1) plus docetaxel (36 mg/m2 iv on day 2 for 3 weeks of a 4-week cycle) to placebo plus docetaxel in patients with chemotherapy-naïve metastatic AIPC. ZA use was not restricted. SRE-free survival was described for the entire group and then compared for patients randomly assigned to DN-101 or placebo and stratified by ZA use. Statistical comparisons were conducted using Cochran-Mantel-Haenszel for incidence and log-rank for SRE-free survival. Results: With a median follow-up of 18.3 months, 33% of subjects experienced at least one SRE and the overall median SRE-free survival was 13 (95% CI 10.5–14.3) months. The incidence of SRE by type was: radiation to bone (18.8%), fracture (10%), spinal cord compression (4%), surgery to bone (0.4%). Eighty-five (34%) patients received ZA. The study was not adequately powered to measure the impact of DN-101 or ZA on SRE endpoints. Exploratory analyses showed a trend for an increase in SRE-free survival (HR 0.78, p = 0.13) of DN-101-treated patients. SRE-free survival and incidence for subgroups were examined ( Table ). Conclusions: This is the first report of SRE incidence in a large, prospective study of docetaxel-based therapy. Improved therapies for reducing SREs in AIPC are needed because the risk of SREs remains high despite the use of modern chemotherapy and ZA. [Table: see text] [Table: see text]

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