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In Advanced Prostate Cancer, Bone Metastasis Is a Killer1

CONFRONT THE DEADLY THREAT OF mCRPC
RISING FROM WITHIN HIS BONES

mCRPC=Metastatic Castration-Resistant Prostate Cancer.

A Growing Threat in the Bones

MORE THAN 90% OF MEN WITH ADVANCED PROSTATE CANCER WILL DEVELOP BONE METASTASES2

Most men with advanced prostate cancer will experience a dangerous transformation in their disease when primary tumor cells invade the bone.1-3

2 Distribution of sites of metastases in 2,607 men diagnosed with Stage IV Prostate Cancer within the SEER-Medicare Database between 1991 and 2009

SEER=Surveillance, Epidemiology, and End Results.

THE BONE SUPPORTS A VICIOUS MIGRATION OF TUMOR CELL METASTASES3-5

Prostate Cancer Preferentially Metastasizes to Bone via “Seed” and “Soil”3,4,6

Advanced prostate cancer is a disease that predominantly resides in the bones. The bone matrix is rich in factors that stimulate the growth of tumor cells and promote the cycle of metastases and bone pathology.3,4

Physical factors in the bone microenvironment, including a supportive vascular system, may also enhance tumor growth.4,6

Diagram of tumor cell metastases in bones through prostate cancer
  1. Tumor cell “seed” leaves the primary tumor3,4,6
  2. Selective soluble factors allow the “seed” to migrate and attach to bone3,4,6
  3. The “soil” microenvironment of the bone is conducive for tumor growth3,4,6
  4. Bone-metastatic cells migrate between distant sites (vs as separate waves from the primary tumor)5
    • Bone metastases spawn additional metastatic sites

PC=Prostate Cancer.

Bone-Metastatic Migration Impacts Survival

SURVIVAL DECLINES WITH THE SPREAD OF METASTASES2

Significant differences exist in OS in mCRPC patients depending on the location of metastasis2

  • Marked reduction in survival is seen in patients with bone plus visceral metastases compared to bone-only metastatic disease
2 Overall survival percentage over time with location of metastases

BONE METASTASIS KILLS1

Bone Metastases Are Correlated With Significant Mortality1

Poor prognosis and higher mortality are associated with bone metastasis in prostate cancer.1

The chart shows the declining survival probabilities at 1, 5, and 7 years in men with and without bone metastases identified from 1999 through 2007 in the Danish National Patient Registry.1

1 Comparison of percent probability of survival with and without bone metastases

IMPACT YOUR PATIENTS’ PROGNOSIS WHEN BONE METASTASES ARE FEWER, EARLY IN mCRPC7

Patients with ≥5 metastases have significantly reduced OS and progression-free survival vs patients with 1 to 4 metastases7

CI=Confidence Interval; mCRPC=Metastatic Castration-Resistant
Prostate Cancer; OS=Overall Survival.

Monitoring the Battle

VIGILANCE IN EVALUATING FOR DISEASE PROGRESSION IS IMPERATIVE8

There Are Multiple Ways to Monitor Disease Progression of Bone-Metastatic Disease

MONITORING MODALITIES CLINICAL CONSIDERATIONS
PSA TESTING
  • Shown to be a predictor of disease progression and survival9
  • Should be used with other disease progression indicators10,11
RADIOGRAPHIC IMAGING
  • Utilized to diagnose metastasis and to identify disease progression12,13
  • Modalities can range in specificity and sensitivity12,13
SYMPTOMS ASSESSMENT
  • Multiple symptoms are associated with bone metastasis14
  • Patients often underreport their symptoms14

While testing for biochemical markers, such as PSA and ALP, and routine or scheduled radiographic scanning are important modalities in disease management, multiple symptoms can frequently indicate progression of metastatic disease.15-17

Therefore, symptom assessments and proactive discussions with patients about changes in symptoms can:

  • Assist in the detection of the onset or worsening of bone metastases16,17
  • Be used to complement other modalities of monitoring disease progression17,18
  • Help guide your clinical approach18,19

ALP=Alkaline Phosphatase; PC=Prostate Cancer; PSA=Prostate-Specific Antigen.

Evaluating Symptoms of Disease Progression

PROACTIVE IDENTIFICATION OF CHANGES IN SYMPTOMS MAY SIGNAL THE NEED FOR A DIFFERENT CLINICAL APPROACH8,15,18,20

Monitoring Symptomatic Progression Is an Important Factor When Considering Your Clinical Approach in Patients With Advanced Prostate Cancer

PATIENTS WITH BONE-METASTATIC DISEASE EXHIBIT A RANGE OF SYMPTOMS BEYOND PAIN THAT EVOLVE OVER TIME

    • Fatigue, generalized weakness19
    • Interference with daily activities21
    • Impaired mobility19
    • Pain and discomfort19,21
    • Interference with sleep21
    • Loss of appetite22
    • Neurologic impairment16
    • Loss of bladder and bowel function19
    • Pathological fracture23
    • Cord compression19

You May Think Your Patients With mCRPC in the Bone Don’t Have Symptoms, but Consider This:

68% OF MEN IGNORE THEIR SYMPTOMS14

Men with advanced prostate cancer are often burdened with symptoms that may cause significant changes in health-related quality of life (HRQOL), but don’t speak up about them. Therefore, a proactive discussion of changes in symptoms is crucial to help evaluate disease progression to determine therapeutic intervention.14,24,25

To see how you may want to discuss the importance of speaking up about symptoms with your patients, visit menwhospeakup.com.

You can also download the Advanced Prostate Cancer Symptom Tracker below to help guide symptom discussions with your patients.

mCRPC=Metastatic Castration-Resistant Prostate Cancer.

Resources for the Battle

RESOURCES

Click on the image to launch the file

  • Monitoring Symptoms of Disease Progression in Advanced Prostate Cancer Video

    Monitoring Symptoms of Disease Progression in Advanced Prostate Cancer Video

    This short video is designed to help you take a proactive approach to identifying disease progression in men with metastatic castration-resistant prostate cancer and bone metastases.

  • Bone Metastases and Mortality in Advanced Prostate Cancer Video

    Bone Metastases and Mortality in Advanced Prostate Cancer Video

    This short video is designed to spotlight the impact of bone metastases on survival in men with metastatic castration-resistant prostate cancer (mCRPC).

To request printed copies of one or more of the resources below, visit our Contact a Bayer Representative page.

  • Bone Metastases & Mortality in Prostate Cancer Slide Deck

    Bone Metastases & Mortality in Prostate Cancer Slide Deck

    Provides a background on bone metastases in prostate cancer, including associated symptoms, and how addressing bone-metastatic disease may improve outcomes.

  • Advanced prostate cancer symptom tracker

    Advanced Prostate Cancer Symptom Tracker

    A form for healthcare professionals to help detect and monitor the onset or worsening of symptoms associated with bone metastases in patients with advanced prostate cancer.

  • Metastatic prostate cancer symptoms flashcard

    Metastatic Prostate Cancer Symptoms Flashcard

    A brief overview of ways to monitor progression of bone-metastatic disease, including the assessment of symptoms.

  • Bone-metastatic migration flashcard

    Bone-Metastatic Migration Flashcard

    A brief overview of bone-metastatic migration in advanced prostate cancer and how it impacts survival.

  • Bone metastases & mortality in prostate cancer monograph

    Bone Metastases & Mortality in Prostate Cancer Monograph

    A comprehensive overview of the development and impact of bone metastases in advanced prostate cancer with a strategy to improve patient management.

  • Bone metastases & mortality in prostate cancer flashcard

    Bone Metastases & Mortality in Prostate Cancer Flashcard

    A brief summary of the symptoms and impact of bone metastases in prostate cancer.

CAN WE BE DOING MORE TO CONFRONT THE DEADLY THREAT OF PROSTATE CANCER IN THE BONE?

Learn more about the fight against mCRPC in the bones

CONTACT A BAYER REPRESENTATIVE

mCRPC=Metastatic Castration-Resistant Prostate Cancer.

REFERENCES

  • 1. Nørgaard M, Jensen AØ, Jacobsen JB, Cetin K, Fryzek JP, Sørensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol. 2010;184(1):162-167.
  • 2. Gandaglia G, Karakiewicz PI, Briganti A, et al. Impact of the site of metastases on survival in patients with metastatic prostate cancer. Eur Urol. 2015;68(2):325-334.
  • 3. Kingsley LA, Fournier PG, Chirgwin JM, Guise TA. Molecular biology of bone metastasis. Mol Cancer Ther. 2007;6(10):2609-2617.
  • 4. Bagi CM. Skeletal implications of prostate cancer. J Musculoskelet Neuronal Interact. 2003;3(2):112-117.
  • 5. Gundem G, Van Loo P, Kremeyer B, et al; ICGC Prostate UK Group. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520(7547):353-357.
  • 6. Yin JJ, Pollock CB, Kelly K. Mechanisms of cancer metastasis to the bone. Cell Res. 2005;15(1):57-62.
  • 7. Tait C, Moore D, Hodgson C, et al. Quantification of skeletal metastases in castrate-resistant prostate cancer predicts progression-free and overall survival. BJU Int. 2014;114(6b):E70-E73. doi:10.1111/bju.12717.
  • 8. O’Sullivan GJ, Carty FL, Cronin CG. Imaging of bone metastasis: an update. World J Radiol. 2015;7(8):202-211. doi:10.4329/wjr.v7.i8.202.
  • 9. Koo KC, Park SU, Kim KH, et al. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels. Prostate Int. 2015;3(1):10-15.
  • 10. Bryce AH, Alumkal JJ, Armstrong A, et al. A post hoc analysis of radiographic progression with nonrising prostate-specific antigen in patients with metastatic castration-resistant prostate cancer (mCRPC) in the PREVAIL study. Ann Oncol. 2016;27(suppl6):vi243-vi265.
  • 11. Mohler JL, Antonarakis ES, Armstrong AJ, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer. Version 2.2017. National Comprehensive Cancer Network; 2017:1-124.
  • 12. Garcia JR, Moreno C, Valls E, et al. Diagnostic performance of bone scintigraphy and (11) C-Choline PET/CT in the detection of bone metastases in patients with biochemical recurrence of prostate cancer. Rev Esp Med Nucl Imagen Mol. 2015;34(3):155-161.
  • 13. Behesti M, Vali R, Waldenberger P, et al. Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study. Eur J Nucl Med Mol Imaging. 2008;35(10):1766-1774.
  • 14. Bayer. Prostate Cancer Symptoms Survey: US Results, 2015. MenWhoSpeakUp website. https://www.menwhospeakup.com/downloads/PP-600-US-1888.pdf. Accessed April 20, 2017.
  • 15. Crawford ED, Stone NN, Yu EY, et al; Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence (RADAR) Group. Challenges and recommendations for early identification of metastatic disease in prostate cancer. Urology. 2014;83(3):664-669.
  • 16. Selvaggi G, Scagliotti GV. Management of bone metastases in cancer: a review. Crit Rev Oncol Hematol. 2005;56(3):365-378.
  • 17. Dupuis LL, Ethier MC, Tomlinson D, Hesser T, Sung L. A systematic review of symptom assessment scales in children with cancer. BMC Cancer. 2012;12(430):1-6. doi:10.1186/1471-2407-12-430.
  • 18. Cotter K, Konety B, Ordonez MA. Contemporary management of prostate cancer [published online February 16, 2016; updated December 25, 2016]. F1000Res. 2016;5(F1000 Faculty Rev):179. doi:10.12688/f1000research.7183.1.
  • 19. Farrell C. Bone metastases: assessment, management and treatment options. Br J Nurs. 2013;22(10):S4,S6,S8-S11.
  • 20. Body JJ, Casimiro S, Costa L. Targeting bone metastases in prostate cancer: improving clinical outcome. Nat Rev Urol. 2015;12(6):340-356.
  • 21. Autio KA, Bennett AV, Jia X, et al. Prevalence of pain and analgesic use in men with metastatic prostate cancer using a patient-reported outcome measure. J Oncol Pract. 2013;9(5):223-229.
  • 22. Hamilton W, Barrett J, Stapley S, Sharp D, Rose P. Clinical features of metastatic cancer in primary care: a case-control study using medical records. Br J Gen Pract. 2015;65(637):e516-e522. doi:10.3399/bjgp15X686077.
  • 23. Jayasekera J, Onukwugha E, Bikov K, Mullins CD, Seal B, Hussain A. The economic burden of skeletal-related events among elderly men with metastatic prostate cancer. Pharmacoeconomics. 2014;32(2):173-191.
  • 24. Resnick MJ, Penson DF. Quality of life with advanced metastatic prostate cancer. Urol Clin North Am. 2012;39(4):505-515.
  • 25. Moro C, Brunelli C, Miccinesi G, et al. Edmonton symptom assessment scale: Italian validation in two palliative care settings. Support Care Cancer. 2006;14(1):30‑37.