Shore Shares Insight on Challenges of Bone Metastases in mCRPC

Neal Shore, MD

Bone metastases in castration-resistant prostate cancer (mCRPC) create a significant problem, Neal Shore, MD, medical director of the Carolina Urologic Research Institute, said in a recent presentation at the 2016 American Urological Association Annual Meeting.

“A bone-metastatic event is really a seminal event,” said Shore, who discussed the prevalence of bone metastases and possible preventative solutions. “It is quite an outstanding biologic and prognostic factor in mortality and, often times, in morbidity.”

Prostate cancer represents 21% of all new cancer cases in men and is the second most common cause of cancer death among American men after lung cancer, reported Shore.

Ninety percent of men with advanced prostate cancer will develop bone metastases.

The problem is so common because prostate cancer has an affinity to metastasize to the bone, as the bone matrix is rich in factors that stimulate the growth of tumor cells and promotes a vicious cycle of metastases and bone pathology, said Shore.

Physical factors in the bone microenvironment may also enhance tumor growth, as malignant cells are widely disseminated in advanced prostate cancer. Metastases most often develops in bones where red marrow is most abundant including the spine, pelvis, and ribs, Shore reported. Metastases may also occur in the skull and long bones.

However, a rising incidence of men are developing advanced disease, he added.

“We have seen perhaps less low-grade disease, but also more high—grade disease,” said Shore. “That is worrisome because these are the patients who really need care in a more proactive way.”

Bone metastases are associated with worse outcomes. A cohort study of more than 23,000 men identified from 1999 through 2007 in the Danish National Patient registry found that the 5-year survival rate was 55.8% (95% CI, 54.9—56.7) in men with prostate cancer without bone metastases, 2.7% (95% CI, 2.2–3.4) in men with bone metastases but no skeletal-related events (SREs), and 0.7% (95% CI, 0.6 –1.0) in men with bone metastases and SREs.

While the statistics are daunting, more work can be done to prevent mortality in mCRPC. Early identification and treatment of bone metastases is key, said Shore.

Additionally, symptoms of bone metastases are not often correctly identified.

“Symptomatology is not exclusively under the heading of ‘pain or no pain,’” said Shore. “Our patient may not be saying, ‘Oh, I’m having this horrific pain in my shoulder or in my back.’ Patients may complain of something entirely different than bone pain, but it is related to that bone metastatic event.”

The most common advanced prostate cancer symptoms reported by men with bone metastases in the United States include fatigue (reported by 85%), all over body pain or aches (55%), numbness or weakness (55%), difficulty sleeping as a result of pain (42%), difficulty doing normal activities (40%), anxiety or distress as a result of pain (40%), vomiting (25%), and loss of appetite (20%).

Fatigue and generalized weakness is the most stressful symptom of which patients complain, said Shore.

These symptoms are often underreported and are not identified as being linked to bone metastases. To combat this problem, people associated with the patient and their care must be made aware of all the possible symptoms of bone metastases, he added.

“We need to get caregivers involved, and spouses and family members involved to help identify these symptoms,” said Shore. “We also need to get the entire healthcare team involved that is treating the patient, whoever that might be—including nurse practitioners, nurses, and physician assistants.”

In addition to underreported symptoms, metastatic disease itself is also not always properly identified. More than 30% of patients with CRPC thought to be nonmetastatic (M0) were in fact metastatic (M1), according to Shore.

A full understanding of the causes of bone metastasis is still lacking.

“There is a migration of disease from the prostate. Why does that happen?” said Shore. “We are really at a crossroads here regarding how we can impose the best therapy, but without much understanding of the physiology of bone metastases.”

More research should be focused in that area, although significant advancements have been made in recent years, explained Shore.

“We are learning so much more and it helps us understand patterns of metastases; it helps us understand what can lead to bone metastases,” he said.

To treat bone metastases in CRPC, it is important to understand the dynamic nature of the disease, and know that the site and location of prostate cancer evolves over time, said Shore. Once bone metastases are identified, treatment approaches need to be reconsidered to focus on treating the metastases. Clinical interventions in bone metastatic disease can significantly impact outcomes.

“At the end of the day our charge as clinicians—whether you are a urologist, medical oncologist, or a radiation oncologist—is to prevent our patients with prostate cancer and, certainly, with bone metastasis, from dying of the disease, and help them maintain a good quality of life while avoiding hospitalization,” said Shore.

Shore N. Bone metastases and mortality in prostate cancer: can we be doing more? Presented at: 2016 American Urological Association Annual Meeting; May 6-10, 2016; San Diego, CA.