Strategies for Managing Chronic Pain in Patients With Bone-Metastatic CRPC

Advanced prostate cancer commonly metastasizes to bone, a cause of chronic, debilitating pain and dangerous complications for patients. When metastatic disease involves only one or a few localized bone tumors, palliative external-beam radiation therapy can help to temporarily alleviate patients’ suffering, improving quality of life during their final months or years. Assessing patients for palliative radiotherapy involves comprehensive physical examinations and symptoms assessments. More than one-third of men with bone-metastatic prostate cancer will survive 12 months from detection of metastasis, necessitating repeated evaluations and single-dose palliative radiotherapy treatments.

Prostate cancer is diagnosed in more than 1 million men around the world each year.¹ Androgen deprivation therapy (ADT) has improved times to progression and survival rates, but many patients will experience progression to castration-resistant disease and bone metastasis, a painful and debilitating condition associated with poor prognoses.²

Most men with metastatic castration-resistant prostate cancer (mCRPC) will develop bone metastasis. Bone-metastatic CRPC frequently causes chronic pain, pathologic fractures (including hip fractures), spinal cord compression, and can lead to dangerous elevations in blood calcium levels. A little more than one-third (35%) of men with bone-metastatic CRPC will survive 12 months from their diagnosis with metastatic disease, and roughly one-third of those patients will live to 3 years.^2,4

Making these remaining months and years of life bearable and meaningful for patients involves close symptom monitoring and management, and supportive care.² More than half of men with bone-metastatic CRPC report living with daily pain, which, along with other debilitating symptoms, can dramatically degrade patients’ physical activity, eating and sleeping patterns, and quality of life.²

In clinical trials, docetaxel, cabazitaxel, abiraterone acetate, and enzalutamide have each been associated with small improvements in times to progression and overall survival times among men with mCRPC.^2-4 Radiopharmaceutical treatments have also shown promise.³ Therapy with strontium-89, samarium-153, or radium-223 are sometimes used when painful bone metastases occur at numerous or distant sites.

Palliative external-beam radiotherapy (EBRT) is a key component of managing chronic pain caused by solitary or few bone metastases, offering temporary reductions in pain.^2,5,6 However, this is only one component of pain management for these patients, and can be undertaken with opioid analgesia.

Single-fraction EBRT is preferred and efficacious; for men with uncomplicated bone metastases (those with no pathologic fractures or spinal cord compression), a single-fraction 8 Gy treatment can temporarily reduce bone metastasis-associated pain.² For those who do experience reductions in pain, maximal relief can require 4 weeks or more from the end of radiotherapy.^2,6

However, up to 40% of patients will experience pain flares in irradiated anatomies.² Dexamethasone (8 mg 1 hour or more before radiotherapy, followed by daily 8-mg doses for 4 days after radiotherapy) can reduce pain flare risk.²

Because pain relief is temporary, some patients will undergo re-assessment and repeat palliative radiotherapy during their remaining months of life.² 

Pain Assessment and Physical Examination

Patient evaluation for palliative EBRT to treat painful bone metastasis involves patient pain history; physical examination; and questions about new neuropathy, balance problems, and recent fall history.² Pain assessment can be done using the OPQRSTUV system:

O Onset. When did the pain start?

P Provoking or palliating. What factors worsen or alleviate pain?

Q Quality. Is your pain throbbing or stabbing, sharp or dull?

R Region and Radiation. Where is the pain and does it radiate or spread?

S Severity. How intense is the pain?

T Treatment. What treatments are you using for pain, and how effective are they? (Also ask about side effects from pain treatment.)

U Understanding impact. How does the pain impact your daily life?

V: Values of patient. What are your goals? Is this level of pain acceptable?

Physical examination should include documentation of neuromuscular measures such as muscle atrophy, lateralizing weakness, and changes in bowel and urinary function, according to Edith Pituskin, RN, PhD, MN(NP), and Alysa Fairchild, MD, in a recent review of chronic pain assessment in patients with bone-metastatic CRPC who undergo evaluation for palliative EBRT.²

Physical examinations should also include physical assessment of “firm pressure to each vertebral body, sternum, and bilateral assessment of the entire pelvis, ribs, scapulae, and clavicles,” they advise.² Each time pressure is applied to these bone structures, the patient should be asked if the pressure causes pain, and painful bones marked on the patient’s skin with ink.²

“These patient-validated painful areas can be correlated with diagnostic imaging to confirm the potential utility of [EBRT], keeping in mind the possibility of referred pain,” they reported. ²

Femoral metastases should prompt assessment of functional pain, they noted, meaning pain occurring when weight is put on the limb with femur tumors.²

“This phenomenon suggests that the supportive bone cortex may be weakened,” Dr Pituskin and Dr Fairchild noted.² “Plain [radiographs] of the femora and pelvis should be ordered to elucidate the extent of cortical damage, with a >30 mm lesion or circumferential cortical involvement [of] >50% significantly predicting fracture.”

These patients should be immediately referred to an orthopedic surgeon and postsurgical multifraction EBRT to prevent additional tumor-associated bone loss or damage.²

Symptoms should be re-assessed 4 weeks after palliative EBRT to determine radiotherapeutic efficacy.

References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi:10.3322/caac.21492
2. Pituskin E, Fairchild A. Prostate cancer with bone metastases: addressing chronic pain from the perspective of the radiation oncology nurse practitioner. Semin Oncol Nurs. 2021;37(4):151175. doi:10.1016/j.soncn.2021.151175
3. Staniszewska M, Iking J, Luckerath K, et al. Drug and molecular radiotherapy combinations for metastatic castration resistant prostate cancer. Nucl Med Biol. 2021;96-97:101-111. doi:10.1016/j.nucmedbio.2021.03.009
4. Svensson E, Christiansen CF, Ulrichsen SP, Roth MR, Sorensen HT. Survival after bone metastasis by primary cancer type: a Danish population-based cohort study. BMJ Open. 2017;7(9):e016022. doi:10.1136/bmjopen-2017-016022
5. Fischer-Valuck BW, Baumann BC, Apicelli A, et al. Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: a hospital-based analysis of pattern of care, RT fractionation scheme, and overall survival. Cancer Med. 2018;7(9):4240-4250. doi:10.1002/cam4.1655
6. Spencer K, Velikova G, Henry A, Westoff P, Hall PT, van der Linden YM. Net pain relief after palliative radiation therapy for painful bone metastases: a useful measure to reflect response duration? A further analysis of the Dutch Bone Metastasis Study. Int J Radiat Oncol Biol Phys. 2019;105(3):559-566. doi:10.1016/j.ijrobp.2019.07.009