These updates will focus on newly available data presented at the annual meeting of the American Urological Association that offer important new or expanded knowledge for patients. We do not intend to cover every piece of new science presented at the meeting.
On Sunday, May 18, the following key pieces of knowledge were presented for the first time:
UK data on the value of salvage cryotherapy in post-radiotherapy failure
Early data from the European PRIAS trial of active surveillance
Data from a randomized trial of tamoxifen therapy vs. tamoxifen prophylaxis in management of gynecomastia
The role of rebiopsy in decision-making regarding treatment options for men with supposed low-risk prostate cancer
Detailed information on each of these presentations is provided below.
The UK Salvage Cyotherapy Study
A single-institution UK study presented by Ismail et al. reported on experience of salvage cryotherapy for recurrent prostate cancer in 100 patients after radiation failure between 2000 and 2005, evaluating the biochemical outcome, complications and management and quality of life. Mean follow-up was 33.5 months. The authors state that this series suggests that slavage cryotherapy is well tolerated, and an effective option for salvage treatment of prostate cancer.
Based on data given below, it certainly appears that there is a generally low morbidity rate (except for erectile dysfunction) and a significant probability of biochemical disease-free survival at nearly 3 years of follow-up for low- and medium-risk patients. However, high-risk patient showed a less favorable outcome and so patient selection is essential to the treatment decision process.
All patients had biopsy-proven recurrent prostate cancer. Biochemical recurrence-free survival (BRFS) was defined using a PSA level < 0.5 ng/mL and the ASTRO definition of biochemical failure. Patients were stratified into three risk groups; high-risk (n = 68), intermediate-risk (n = 20) and low-risk (n = 12).
The authors reported no operative or cancer-related deaths. The 5-year actuarial BRFS was 73, 45 and 11 percent for the low, intermediate and high-risk groups respectively. Complications included incontinence (13 percent), erectile dysfunction (86 percent), lower urinary tract symptoms (16 percent), prolonged perineal pain (4 percent), urinary retention (2 percent), and rectourethral fistula (1 percent).
The European PRIAS Trial
Roemeling et al. provided early data from the Prostate Cancer Research International: Active Surveillance (PRIAS) international active surveillance program. This study was designed to offer insight into the overall and cause-specific survival of screen-detected men who were initially managed expectantly and would have complied with the PRIAS inclusion criteria.
One or two biopsy cores invaded with prostate cancer
Biopsy Gleason score 3 + 3 = 6 or less.
These inclusion criteria were retrospectively assessed against the 1,629 prostate cancers detected in the first two screen rounds of the ERSPC; Rotterdam section. Diagnoses were based on lateralized sextant biopsies. The causes of death were reviewed by an independent committee and were complete through January 2006.
Of 628 patients with screen-detected cancers in the ERSPC study that matched the PRIAS inclusion criteria (628/1,629, 39 percent), 183 men (183/628, 29 percent) elected active surveilance (”expectant management”). Their median PSA level at diagnosis was 4.0 ng/mL and their median age was 67 years. During the mean follow-up of 6.6 years a total of 26 men (14 percent) died, but none died from prostate cancer. The calculated 10-year overall survival was 77 percent, which is in sharp contrast to the calculated 10-year cause-specific survival of 100%.
The authors concluded that, based on the entry criteria and the 100 percent disease-specific survival, a large proportion of men in the contemporary screening series would have been candidates for active surveillance.
Gynecomastia and Tamoxifen Management
Men receiving bicalutamide (Casodex) as a form of hormone therapy for prostate cancer are at well-regognized risk for tenderness and swelling of the breasts. Tamoxifen has been used in therapy and prophylaxis of gynecomastia and breast pain induced by bicalutamide. However, tamoxifen dose and treatment schedule are not definitively established. Also, it is unclear whether prophylaxis is more effective than therapy delivered at early onset of gynecomastia.
A group of Italian researchers compared the prophylactic (preventive) activity of tamoxifen 10 mg once daily with its therapeutic activity at 20 mg once daily at the first signs of gynecomastia in patients taking bicalutamide 150 mg/day for prostate cancer. The study ran between June 2005 and June 2007. A total of 176 patients (median age 74 years)were randomized at the time of starting bicalutamide in to two arms:
Arm A — Tamoxifen 20 mg/day given for 1 year starting within 1 month of onset of gynecomastia
Arm B — Tamoxifen 10 mg/day given for 1 year starting at the initial prescription of bicalutamide.
Routine laboratory tests, testosterone levels , PSA levels, and follow-up visits were obtained at 1 month and then 3-monthly. Gynecomastia and breast pain were evaluated by the patients using a self-administered visual analog scale. Gynecomastia was classified into four grades (0-4) by physical exam.
Based on follow-up at various times between 3 and 24 months, gynecomastia increased in arm A from 34 percent after 3 months of bicalutamide therapy up to 78 percent after 12 months. When tamoxifen 20 mg was given, all patients showed a reduction in gynecomastia (to 56 percent of cases) and breast pain (to 34 percent of cases). However, neither gynecomastia nor breast pain were entirely eliminated. Two patients interrupted the treatment after 3 months due to dizziness and 4 patients (5 percent) did not consider the gynecomastia to be important and did not take the drug.
In contrast, the incidence of gynecomastia and breast pain was significantly reduced by tamoxifen 10 mg prophylaxis (but again, they not completely abolished). Both gynecomastia and breast pain occurred in up to 25 percent of patients after 1 year of bicalutamide plus tamoxifen 10 mg administration. No patient interrupted the treatment due to intolerance. There were no significant differences emerged Arms A and B in terms of PSA response and plasma testosterone levels.
The authors conclude that bicalutamide-induced gynecomastia and breast pain, although reduced, persist in patients treated post-onset with tamoxifen 20 mg/daily, but that bicalutamide-induced gynecomastia is significantly reduced, although not abolished, by prophylaxis with tamoxifen 10 mg/daily.
Rebiopsy of Men Supposed to Be at Candidates for Active Surveillance
Active surveillance (AS) is an increasingly important management regimen for patients with low-risk prostate cancer, particularly those patients of 70 years or older. Decision making is often based on pre-treatment PSA, clinical stage, and prostate biopsy results.
Berglund et al. from Memorial Sloan Kettering Cancer Center reported their experience with immediate repeat biopsy in patients eligible for AS. They retrospectively reviewed consecutive patients undergoing repeat biopsy within 3 months of a first positive biopsy in the period between 2002 and 2007. Patients were considered eligible if they had a PSA < 10 ng/mL, clinical stage < T2b, Gleason grade < 3, fewer than three positive biopsy cores, and no single biopsy core with >50 percent involvement of prostate cancer.
A total of 104 patients met the eligibility criteria. Of the repeat biopsies performed: 27 biopsies (26 percent) were negative; 58 biopsies (56 percent) had a Gleason score of < 6; 17 patients (16 percent) had a Gleason score of 7; one patient had Gleason score of 9; 10 patients (10 percent) had more than 3 cores involved on repeat biopsy; and 12 patients (12 percent) had > 50 percent involvement of at least one core.
A total of 27/104 patients (26 percent) were upgraded or upstaged. Sixty patients eventually underwent surgery, with no biochemical recurrences at a median follow-up of 13 months, except for one patient who developed metastatic disease at 46 months following surgery.
The authors concluded that immediate repeat biopsy in patients with prostate cancer being considered for AS resulted in more than 25 percent being upgraded or upstaged, thus yielding improved discrimination as to whom is the best candidate for AS.