The prostate cancer news update: Tuesday, August 5

So after a few days becalmed in a world of minimal prostate cancer news … we have a fine controversy to revisit and some other interesting titbits to gnaw on …

First, the US Preventive Services Task Force has revised its guidelines on screening for prostate cancer, and everyone will be in an uproar for days. For our take on this, click here.

Second, Porter et al. have developed and validated (internally) a new nomogram for the assessment of risk of metastatic prostate cancer subsequent to radical prostatectomy. Their model is based on the probability of metastatic progression of prostate cancer in 752 patients treated with radical prostatectomy with a mean follow up of 11.6 years. A total of 85/752 patients (11.3 percent) developed metastatic progression. The 5, 10, 15, and 20-year actuarial rates of metastatic progression-free survival were, respectively, 95.9, 90.5, 84.8 and 80.5 percent. Pathological stage T3, elevated radical prostatectomy Gleason sum, and delivery of adjuvant radiotherapy represented independent predictors of metastatic progression, along with a fourth variable describing the presence of co-morbidities. The nomogram achieved 80.2, 77.7, 77.6 and 76.0 percent accuracy in predicting metastatic progression at 5, 10, 15 and 20 years after radical prostatectomy. The authors claim that this nomogram is able to “accurately predict the conditional probability of metastatic progression up to 20 years after radical prostatectomy.”

Third, Gignac et al. report that “Outcome assessment policies are highly variable in phase 2 studies of castration-resistant prostate cancer patients, despite published guidelines designed to standardize authentication of disease progression.” They go on to note that estimated error in progression-free survival (PFS) in such trials can exceed 6 weeks per cycle because of variations in the assessment schedules. They conclude that any comparisons of PFS times between studies must be made with great caution. The problem is that clinical progression is easier to identify than clinical response in clinical trials in patients with advanced prostate cancer. The authors reviewed phase 2 clinical trials of cytotoxic agents in castration-resistant metastatic prostate cancer over 5 years to evaluate the policies determining extent of disease and the definitions of disease progression. A model was created to define the degree of error in estimating PFS in three hypothetical patient cohorts ( with median PFS of 12, 24, and 36 weeks) when the frequency of outcome assessments varies. Imaging policies for trial entry were heterogeneous, as were the type, timing, and indications for outcome assessments. In the simulation, error in the reported PFS varied according to the interval between assessments. The difference between the detected and the true PFS could vary as much as 6.4 weeks per cycle, based exclusively on the variability of assessment schedules tested.

Finally, Martin et al. report that screening for early stage prostate cancers on the basis of lower urinary tract symptoms (LUTS) may not be justified.  Although screening based on the presence of LUTS is frequently employed, the evidence linking LUTS with prostate cancer is limited. Martin and colleagues assessed the association of LUTS with a subsequent prostate cancer diagnosis in a prospective cohort study based on 21,159 Norwegian men who completed baseline questionnaires, including the International Prostate Symptom Score (IPSS) questionnaire, between 1995 and 2007 as part of the second Nord-Trøndelag Health Study (HUNT 2). Men were followed-up for prostate cancer incidence and mortality from the date of clinical examination to the end of 2005. During a mean of 9 years follow-up, 518 incident prostate cancers were diagnosed (in 2.4 percent of the study population) and 74 men died from prostate cancer (0.35 percent). Men with severe LUTS had a 2.26-fold increased risk of prostate cancer compared to men reporting no symptoms. A positive association was observed for localized, but not advanced, cancers. They conclude  that LUTS are positively associated with localized, but not advanced or fatal, prostate cancer, suggesting that urinary symptoms are not caused by prostate cancer.

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