1. PSA and BRCA: an IMPACT update

Men with germline BRCA1 and BRCA2 mutations not only have an increased risk of prostate cancer, but research also suggests that these men develop more aggressive disease, are younger at diagnosis, have a higher rate of lymph node involvement and distant metastases at diagnosis, and higher mortality rates. Moreover, BRCA2 mutant localised cancer has a mutational profile that more closely resembles metastatic than localised disease, therefore supporting early detection in this at-risk population.

The IMPACT study is an international multi-centre study evaluating the role of PSA screening in men with a BCRA1 or BRCA2 mutation. To date, around 3000 men have been recruited from 20 countries across the world. The objective of the present study was to establish whether PSA values and/or PSA velocity (PSAV) were associated with prostate cancer and aggressive tumours among men at risk enrolled in the IMPACT trial.

The study found that overall, the PSA level and PSAV at diagnosis were higher in men diagnosed with cancer (3.7 vs 0.9 ng/ml, p<0.0001 and 0.56 vs 0.02 ng/ml/year, respectively). In addition, whilst there was a significant interaction between PSA level at diagnosis and BRCA status (p=0.031), PSAV did not provide any additional information for BRCA carriers (p=0.4). However, PSAV proved predictive of any grade cancer within the group of BRCA2 carriers (p=0.024), suggesting that a high PSAV in an individual with a BRCA2 mutation could be used both as an indicator of prostate cancer and as an indication for biopsy, leading to diagnosis of lower grade cancers in BRCA2 carriers.

In summary, PSA is more predictive of prostate cancer in BRCA carriers than non-carriers. PSAV was not found to be an independent prognostic factor in BRCA carriers, and this study found no evidence that PSAV aids decision making for indication of biopsy or frequency of follow-up in BRCA carriers.

2.Androgen deprivation therapy and risk of rheumatoid arthritis in localised prostate cancer

An American study has reported a potential link between androgen deprivation therapy (ADT) and rheumatoid arthritis. Whilst it is known that androgens are generally immunosuppressive, (which may partially explain the higher incidence of autoimmune diseases in women and hypogonadal men) to date there has been no evidence to support a role for ADT in the development of autoimmune diseases.

 

The study looked at 105,303 men diagnosed between 1992 to 2006 with grade I-III prostate cancer aged 66 and older, using the Surveillance, Epidemiology, and End Results-Medicare (SEER) linked database. 43% (N=44,785) of the study cohort had received ADT.

Overall, patients who received any ADT had a 23% increased risk of receiving a new diagnosis of rheumatoid arthritis (HR 1.23, 95% CI 1.09-1.40, p=0.001). Furthermore, at 5 years, 5.1%, 5.65% and 5.8% of men who received 1-6, 7-12 and over 13 months of ADT, respectively, were diagnosed with RA, compared to 4.4% of those who did not (all p=0.001). Compared with no ADT, 1-6 months, 7-12 months, and over 13 months of ADT was associated with 19% (HR 1.19, 95% CI 1.06-1.33, p=0.003), 29% (HR 1.29, 95% CI 1.05-1.57, p=0.014), and 33% (HR 1.33, 95% CI 1.13-1.56, p<0.001) increased risks of a new rheumatoid arthritis diagnosis, respectively.

There are a couple of limitations to the study: firstly, the study cohort was limited to men aged 66 and older, and so these results may not be reflective of the association between ADT and new rheumatoid arthritis diagnoses for patients younger than this. Secondly, it is possible that some patients were receiving androgen receptor (AR) antagonists by way of monotherapy, which was not recorded in this study. Therefore, the risk of rheumatoid arthritis diagnoses associated with AR antagonist monotherapy could not be determined.

Consistent with the immunosuppressive effects of androgens, this study suggests an association between the use of ADT and being diagnosed with rheumatoid arthritis in elderly men with prostate cancer. The study recommends that physicians should discuss rheumatoid arthritis as a potential side-effect before initiating ADT, particularly if a long course is anticipated.

 

3. Socioeconomic status and its effect on cancer outcomes

A study in Sweden has shown that patients with high socioeconomic status (SES) have better cancer outcomes than patients with a low SES when using the national health care system.

 

Men in the highest income quartile had a higher proportion of low-risk prostate cancer compared to men in the lowest quartile of income (39% vs 18%). Distant metastases were less common in men with highest income (6%) compared to men with lowest income (19%). Men were more likely to receive a prostate cancer diagnosis after PSA testing as a part of a health-check-up if they were in the highest income quartile than men in the lowest quartile (OR 1.60, 95% CI=1.5-1.77) and were less likely to receive a diagnosis of advanced prostate cancer (OR 0.57, 0.54-0.60).

 

In terms of treatment, men with higher incomes were more likely to receive curative treatment for intermediate and high-risk prostate cancer (OR 1.77, 1.61-1.95), were also less likely to have to wait more than 3 months for radical prostatectomy (OR 0.77, 0.69-0.86), have positive surgical margins following prostatectomy (OR 0.8, 0.71-0.90), and of having a wait time for radiotherapy exceeding the median (OR 0.81, 0.68-0.96). Men with high education were more likely to receive active surveillance than men with low education (OR 1.28, 1.06-1.55).

 

All-cause and prostate cancer-specific mortality was lower in men with high SES. In men above age 65 with low-risk prostate cancer, all-cause mortality was two-fold lower in men with the highest compared to lowest incomes (12% vs 30%; p<0.001).

 

High educational level is associated with high health-awareness and the ability to navigate the health care system. However, the effects of other factors, such as health-seeking behaviour, life-style and health beliefs and awareness could not be addressed in this study. It is also important to note that more men with a high SES received an over-diagnosis. The underlying reasons for differences in patient outcomes according to SES remain unknown. However, the findings of this study highlight the importance of guideline adherence to ensure optimal and equal care.

 

 

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