Person:

Mahal, Brandon

Chronic pain arising from various pathological conditions such as osteoarthritis, low back or spinal injuries, cancer, and urological chronic pelvic pain syndromes presents significant challenges in diagnosis and treatment. Specifically, since the underlying cause of these pain syndromes is unknown or heterogeneous, physicians diagnose and treat patients based on the symptoms presented. Nerve growth factor (NGF) has been recognized as an important mediator of chronic pain in many pathological conditions, and has been shown to be upregulated in a subset of individuals suffering from such pain syndromes. These findings have led to the development of anti-NGF monoclonal antibodies such as tanezumab as potentially effective therapeutics for chronic pain. Although tanezumab has reached Phase II and III clinical trials, the trials of anti-NGF antibodies were halted due to safety concerns. Some of these trials of anti-NGF treatment have had statistically significant decreases in pain, while others have yielded inconclusive results. These findings are suggestive of, though do not prove, target (NGF) neutralization in chronic pain syndromes. A biomarker-driven anti-NGF clinical study layout is proposed that incorporates NGF measurements in the relevant samples before and after treatment, in addition to collecting the pain scores. This approach might not only confirm the mechanism of tanezumab’s action in these chronic pain patients, but should establish NGF levels as a predictive biomarker for patients who can benefit from anti-NGF treatment, thereby creating a personalized approach to pain treatment.

Background: The risk of prostate cancer-specific mortality (PCSM) following a diagnosis of prostate cancer may improve after patients have survived a number of years after diagnosis. We sought to determine long-term conditional PCSM for patients with stage T4, N1, or M1 prostate cancer. Methods: We identified 66,817 patients diagnosed with stage IV (T4N0M0, N1M0, or M1) prostate cancer between 1973 and 2011 using the Surveillance, Epidemiology, and End Results (SEER) database. Conditional five-year PCSM was evaluated for each group of patients at 5, 10, and 15 years of survival according to the Fine & Gray model for competing risks after adjusting for tumor grade, age, income level, and marital status. Race-stratified analyses were also performed. Results: There were 13,345 patients with T4 disease, 12,450 patients with N1 disease, and 41,022 patients with M1 disease. Median follow-up among survivors in the three groups was 123 months (range: 0-382 months), 61 months (range: 0-410 months), and 30 months (range: 0-370 months), respectively. Conditional PCSM improved in all three groups over time. Among patients with T4 disease, 5-year PCSM improved from 13.9% at diagnosis to 11.2%, 8.1%, and 6.5% conditioned on 5, 10, or 15 years of survival, respectively (p < 0.001 in all cases). In patients with N1 disease, 5-year PCSM increased within the first five years and decreased thereafter, from 18.9% at diagnosis to 21.4% (p < 0.001), 17.6% (p = 0.055), and 13.8% (p <0.001), respectively. In patients with metastatic disease, 5-year PCSM improved from 57.2% at diagnosis to 41.1%, 28.8%, and 20.8%, respectively (p < 0.001). White race was associated with Conditional mortality after T4, N1, or M1 prostate cancer--2 a greater increase in conditional survival compared to non-white race among those with T4 or N1 disease. Conclusions: While patients with T4, N1, or M1 prostate cancer are never “cured,” their odds of cancer-specific survival increase substantially after they have survived for 5 or more years. Physicians who take care of patients with prostate cancer can use this data to guide follow-up decisions and to counsel newly diagnosed patients and survivors regarding their long-term prognosis.

Objectives: We evaluated whether African Americans (AA) with intermediate to high-risk prostate cancer receive similar treatment as white patients and whether any observed disparities are persistent with time, across age groups, or by insurance status.

Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify 128,189 men with localized intermediate to high-risk prostate cancer (PSA >= 10 or Gleason >= 7 or T stage >= T2b) diagnosed from 2004 – 2010. We used multivariable logistic regression analyses to determine the impact of race on the receipt of definitive treatment and Fine-Gray competing risks regression to determine the impact of race on cancer mortality.

Results: After adjusting for treatment, demographics, and prognostic factors, AA men had a higher risk of prostate-cancer specific mortality (AHR 1.12; 95% CI 1.01 – 1.25; P = 0.03). AA men were significantly less likely to receive curative-intent treatment than white men (Adjusted Odds Ratio [AOR] 0.82; 95% CI 0.79 – 0.86; P < 0.001). There was no evidence of this disparity narrowing over time (Pinteraction 2010 vs. 2004 = 0.490). Disparities in the receipt of treatment between AA and white men were significantly larger in high-risk (AOR 0.60; 95% CI 0.56 – 0.64; P < 0.001) than in intermediate-risk disease (AOR 0.92; 95% CI 0.88 – 0.97; P = 0.04), (Pinteraction < 0.001). The adjusted odds of receiving definitive treatment for AA vs. white men was 0.67 (95% CI 0.62 – 0.73; P <0.001) among men age <70, but was 0.60 (95% CI 0.55 – 0.66; P <0.001) among men age >=70, suggesting increased racial disparity in the receipt of definitive treatment among older men (Pinteraction = 0.01). Among uninsured men, the adjusted OR for definitive treatment for AA vs. white was 0.38 (95% CI 0.27 – 0.54; P < 0.001), but among insured men, the adjusted OR was 0.62 (95% CI 0.57 – 0.66; P<0.001), (Pinteraction = 0.01).

Conclusions: AA men with high-risk prostate cancer were significantly less likely to receive potentially life-saving definitive treatment when compared to white men. This disparity is worse in high-risk disease and among men age >=70, and is not improving over time. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive prostate cancer. Factors underlying these treatment disparities should be urgently studied, as they are potentially correctable contributors to excess prostate cancer mortality among AA patients.