Prostate cancer news review: Thursday, July 24

Newly published studies today include data on:

  • Risk for patients with prostate atypia on biopsy having a subsequent diagnosis of prostate cancer
  • Patterns of failure of patients treated with brachytherapy for localized disease
  • Quality of life following differing types of radiotherapy
  • Second-line antiandrogen therapy following initial failure of a first-line antiandrogen in advanced prostate cancer
  • Mood and cognitive changes in men receiving intermittent androgen deprivation therapy

Abouassaly et al. have reported data on the risk that identification of atypia in prostate biopsy tissue is associated with a subsequent diagnosis of prostate cancer using saturation biopsy methods. Atypia is present in ~ 5 percent of traditional biopsy specimens. Historically, this finding carries a 40 percent risk of prostate cancer on subsequent biopsy. The authors identified 57 patients with a diagnosis of atypia who underwent repeat biopsy between January 2001 and August 2007. These patients’ charts were reviewed for all relevant clinical and pathological information. Median patient age was 62 years (range 46 to 79). Of the 57 patients, 19 (33 percent) had atypia diagnosed on saturation biopsy (20 cores or greater) (Group 1), whereas 38 (67 percent) had atypia diagnosed with a more traditional biopsy technique (12 cores or fewer) (Group 2). All patients subsequently underwent saturation repeat biopsy a median of 5 months after the original biopsy. Eight patients in Group 1 (42 percent) were found to have cancer on rebiopsy compared to 15 patients (39.5 percent) in Group 2. Only one patient in Group 1 had a Gleason score of ≥ 7; however, 5/15 patients in Group 2 (33 percent) had a Gleason score of of ≥ 7. Patients with cancer were less likely to have inflammation on initial biopsy (p = 0.05). The authors conclude that a finding of atypia on prostate biopsy is associated with a high likelihood of underlying malignancy, regardless of the number of cores taken on initial biopsy. Inflammation in the initial biopsy may create a false-positive finding of atypia.

Stock et al. have published log-term data on the patterns of failure after the brachytherapy management of localized prostate cancer from their institution. Between 1990 and 2008, they treated 2,869 patients with brachytherapy and 213 (7.4 percent) experienced a PSA failure by the Phoenix definition. Of these 213 patients, 33.5 percent were low risk, 18.5 percent intermediate risk, and 58 percent high risk. Of the 119 patients biopsied post-treatment, 36 (30 percent) had a least one positive biopsy. PSA doubling time was  predictive of a positive biopsy. Patients with doubling times of ≤ 3, > 3-6, ≥ 6-10, and > 10 months had positive biopsy rates of 9, 18, 36, and 42 percent, respectively (p=0.01). The actuarial rate of remaining free from distant metastases at 10 years was 73 percent. Patients with PSA doubling times of ≤ 3, > 3-6, ≥ 6-10, and > 10 months had freedom from distant metastases rates of 0, 74, 78, and 94.5 percent at 10 years, respectively (p<0.0001). PSA doubling time and time to PSA failure were the most significant predictors of developing distant metastases. The authors conclude that a third of their patients who fail brachytherapyfor localized disease have harbored a component of local failure and a quarter had clinical metastases. PSA doubling time can be used to help predict the source of a rising PSA.

Joseph et al. have reported that (based on a study of 111 patients) they found no difference in quality of life at 1 year after treatment between men who received high dose rate brachytherapy (HDRBT) alone and those who received a combination of HDRBTand external beam radiotherapy.

Suzuki et al. have published the results of a multicenter trial in Japan investigating the value of switching patients to an alternate nonsteroidal antiandrogen following failure of combined androgen blockade with a first-line antiandrogen (e.g., switching patients from leuprolide acetate + bicalutamide to leuprolide acetate + flutamide after failure of the first regimen). The study included 232 patients with advanced prostate cancer who were initially treated with combined androgen blockade, including surgical or medical castration combined with a non-steroidal antiandrogen. If a patient relapsed while on first-line therapy, the antiandrogen was discontinued and the patient was monitored for antiandrogen withdrawal syndrome. An alternative antiandrogen was then administered. The results of this trial showed that the incidence of antiandrogen withdrawal syndrome after initial combined androgen blockade was 15.5 percent for bicalutamide and 12.8 percent for flutamide. A PSA decrease after antiandrogen withdrawal was a prognostic factor. Nonsteroidal antiandrogens as alternative therapy in patients with relapse after the initial androgen blockade were effective (PSA decrease >50 percent) as second line androgen blockade. Of the 232 patients, 142 (61.2 percent) showed a PSA decrease in response to an alternative antiandrogen. These responders had significantly better survival than non-responders, suggesting that responsiveness to second-line therapy predicts increased survival.

A small study by Cherrier et al. has investigated mood and cognitive changes in otherwise healthy men with prostate cancer prior to, during, and following treatment with androgen deprivation (ADT). Twenty hormone-naïve patients with no evidence of metastases and with a rising PSA were treated with intermittent ADT. Their treatment comprised and “on treatment” period of 9 months of complete androgen blockade with leuprolide and flutamide followed by an “off treatment” period. Cognitive function tests and mood measures were administered at baseline, after 3 and 9 months of ADT, and after 3 months off treatment. Twenty healthy control patients without prostate cancer (range matched for age and education) were tested at the same time intervals. The ADT patients apparently showed a significant decline in spatial reasoning, spatial abilities, and working memory during treatment compared with baseline. No changes were noted for measures of verbal or spatial memory, selective attention, or language. Significant changes in self-rated mood such as increased depression, tension, anxiety, fatigue and irritability were evident during treatment compared with baseline for the ADT patients. No significant changes in either cognitive tests or mood measures were noted for the healthy control group. The authors conclude that 9 months of combined androgen blockade may result in some adverse changes in cognition and mood. However, many but not all of these changes can return to baseline after cessation of ADT.

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