End-of-Life Prostate Cancer-Related Complications Characterized

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Men with advanced prostate cancer (PCa), especially those with castration-resistant prostate cancer (CRPC), have an elevated risk of disease-related complications near the end of life, including spinal cord compression and renal failure, according to study findings presented at the American Society of Clinical Oncology's 2018 Annual Meeting in Chicago.

“Many patients with prostate cancer can expect excellent survival outcomes, even those with metastatic disease,” lead investigator Divya Yerramilli, MD, of Massachusetts General Hospital in Boston, told Renal & Urology News. “However, there has been no comprehensive examination of how patients with prostate cancer experience major disease-related complications, such as cord compression and renal failure at the end of their lives. In other words, patients with prostate cancer live a long time, but a significant proportion of these patients suffer for a long time, too.”
The study by Dr Yerramilli's team included 2603 men diagnosed with PCa and who had died at the end of a 10-year follow-up period. The men had a mean age of 67.6 years at diagnosis and a mean age at death of 70.1 years. The cohort consisted of 490 patients with low/intermediate-risk PCa, 617 with high-risk PCa, and 1005 with metastatic disease at diagnosis. Of those with metastatic disease, 519 patients had CRPC and 481 had castration-sensitive PCa.

Radiologic evidence of bone metastases developed in 7.2% of patients with low/intermediate-risk PCa (stage T2c or less, Gleason score 7 or less, PSA 20 ng/mL or less) compared with 28.1% of men with high-risk PCa (stage T3, Gleason score 8–9, PSA greater than 20 ng/mL) and 40.9% of those with metastatic (T4, N1, or M1) disease. Pathologic fracture due to bone metastases occurred in 1.4%, 6.2%, and 16.3% of men with low/intermediate-risk, high-risk, and metastatic disease, respectively, according to Dr Yerramilli's group.

Spinal cord compression developed in 2.1%, 5.2%, and 18.8% of these groups, respectively. Ureteric obstruction developed in 2.5%, 10.6%, and 15.5%, respectively. Renal failure due to ureteric obstruction developed in 0.6%, 6.5%, and 10.3%, respectively.

Castration resistance developed at a median of 4.5, 2.9, and 1.2 years from diagnosis in patients with low/intermediate-risk, high-risk, and metastatic disease, respectively. Radiologic evidence of bone metastases in these groups developed at a median of 4.2, 2.9, and 1.3 years from diagnosis. Spinal cord compression developed at a median of 4.5, 2.9, and 1.3 years, and ureteric obstruction developed at a median of 2.7, 3.6%, and 1.6 years from diagnosis.
Compared with patients who had castration-sensitive PCa, those with CRPC had 2-fold increased odds of bone metastases and ureteric obstruction. They also had 64% and 56% greater odds of pathologic fracture due to bone metastases and spinal cord compression, respectively. All of these increased risks were statistically significant.

“Our team hopes that these data, presented by risk group at diagnosis, allows providers to explain the natural history of this disease to their patients, and discuss upfront management strategies in the context of the development of these major disease-related events,” Dr Yerramilli said. “For example, for a patient with metastatic disease at diagnosis, we know that about a fifth of patients develop cord compression. Therefore, should this patient develop back pain, it should raise concern for the risk of cord compression.”

The researchers hope the new findings provide opportunities to study early palliative interventions, such as screening and treatment of spinal metastasis, targeting improvements in bone health, or exploring strategies to manage urinary obstruction before it leads to renal failure, Dr Yerramilli said