High-risk PC Research Articles

Percent Positive Biopsy Cores and the Risk of Death from Prostate Cancer in Men Treated with Radiation and Androgen Deprivation Therapy

Purpose/Objective(s): Randomized trials that showed superiority of adding androgen deprivation (ADT) to radiation (RT) in terms of survival did not include pre-randomization stratification by percent positive biopsy cores (PPB), a known prostate cancer prognostic factor. The purpose of the current study is to evaluate the impact of adding 6 months of ADT to RTon the risk of prostate cancer-specific mortality (PCSM) stratified by low or high PPB using data from a prospective randomized controlled trial for men in good health with intermediate or high-risk PC. Materials/Methods: From December 1, 1995 to April 15, 2001, 206 men with localized but intermediate or high-risk PC were randomized to receive either RT alone or in combination with 6 months of ADT. A subgroup of the 149 men with no or minimal comorbidity, determined using the ACE27 comorbidity metric, comprised the study cohort. A Fine and Gray competing risks univariable and multivariable regression was used to ascertain whether increasing PPB was associated with an increased risk of PCSM adjusting for age, PSA at randomization, biopsy Gleason score, clinical T-category and treatment received. Cumulative incidence estimates of PCSM describing the impact of treatment with RT alone or RT + ADT

Does Gleason score (GS) predict efficacy of abiraterone acetate (AA) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)? An analysis of AA phase 3 trials.

20 Background: GS is strongly prognostic in localized PC but is less so in mCRPC (Halabi S, J Clin Oncol 2003; Armstrong AJ, Eur J Cancer 2010). Pts with high-risk localized PC and high GS who undergo radiation therapy benefit from long-term androgen deprivation therapy (Horwitz EM, J Clin Oncol 2008). In mCRPC, the impact of GS at initial diagnosis on response to AA therapy is unknown. We retrospectively evaluated efficacy outcomes in pts with mCRPC treated with AA plus prednisone (P) vs P alone in pivotal studies COU-AA-301 (post-docetaxel) and COU-AA-302 (chemo-naive) by GS (≥ 8 or < 8). Methods: 1,048 pts in COU-AA-301 and 996 in COU-AA-302 with mCRPC treated with AA 1 g + P 5 mg po BID or placebo + P had GS data at diagnosis. Efficacy end points evaluated: overall survival (OS), radiographic progression free survival (rPFS), and time to prostate-specific antigen progression (TTPP) (de Bono JS, NEJM 2011; Fizazi K, Lancet Oncol 2012; Ryan CR, NEJM 2013). Distributions and medians were estimated by the Kaplan-Meier method, and hazard ratio (HR) and 95% confidence interval were estimated by the Cox model. Results: Proportion of pts with GS ≥ 8 and GS < 8 was similar across treatment groups and studies. Outcomes by GS are summarized in the Table. Conclusions: GS (≥ 8 or < 8) at initial diagnosis was not predictive of treatment benefit of AA + P vs P alone in post-docetaxel and chemo-naïve pts with mCRPC, with both groups benefiting. In this era of novel androgen signaling targeted agents, GS may not be relevant in predicting efficacy with AA for pts with mCRPC. Clinical trial information: NCT00638690, NCT00887198. [Table: see text]

PO-0728: Influence of whole pelvis radiotherapy in high risk PC outcomes treated with radical intention. RECAP data base

PO-0728: Influence of whole pelvis radiotherapy in high risk PC outcomes treated with radical intention. RECAP data base

Radical Prostatectomy for High-risk Prostate Cancer

The prostate-specific antigen (PSA) era has changed the pattern of prostate cancer at presentation. Patients now present with lower-stage, lower-risk disease. However, some patients continue to present with high-risk prostate cancer (high-risk PC), and the effect of PSA introduction on outcome is less clear. This review highlights the salient features of why radical prostatectomy should be considered in the management of men with high-risk PC (Gleason score 8-10, marked increase in PSA levels and advanced clinical T stage). Radical retropubic prostatectomy (RRP) can provide durable local control, long-term cancer-specific survival and accurate pathologic staging, and may guide further individualized treatment. For these reasons, RRP remains the best single treatment of high-risk PC in operable patients.

Prostate cancer‐specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high‐risk factors

Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P <or= .001). The solitary presence of a PSA velocity >2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC.

Investigation of a Cluster of Pediatric Cardiac [PC] Surgical Site Infections [SSI] Leads to Discovery of Significant Difference in PC SSI Rates by Specific Procedure [SP

ISSUE: Pediatric cardiac surgery is becoming increasingly complicated and involving more compromised children. In our 160 bed Children's Center, we perform 200 PC surgeries annually. For the past 2 years, we have tracked SSI rates among high-risk PC patients. SSI are defined using NNIS criteria. Because no national benchmarks for PC SSI rates exist, we compare our SSI rate to those in the past. In July 2005, we investigated a cluster of PC SSI which did not increase our mean infection rate [5%]. The cluster was identified because patients had their surgery during the same week. PROJECT: An outbreak investigation was undertaken and included a literature search, a line list that encompassed potential risk factors [type of hardware, underlying diagnosis, age, length of surgery] and potential commonalities [infecting organism, operating room (OR) number] for the cluster cases, and direct observation in the OR. In addition, PC cases for the past 18 months were re-analyzed. As part of the re-analysis, we examined our SSI rates by SP as defined by NNIS ICD9 procedure codes. RESULTS: We were unable to detect any commonalities that would account for the SSI cluster. There were no digressions from best practices noted during our OR observation. However, the analysis of our infection rates by SP using the NNIS ICD9 codes revealed that our infection rate for children having cardiac vascular surgery [CVS] was significantly higher [10.4%] compared to those having surgery on the valves or septum of the heart [2.6%] [P = 0.03]. LESSONS LEARNED: Even though our PC SSI rate [5.49%] for the first 6 months of 2005 was comparable to our cummulative mean infection rate [5%], looking at the data in a different way revealed a problem we were not aware of. Now that we are aware of the increased rate in our CVS patients, we can work with our Cardiac Surgery Team to develop appropriate interventions. This may suggest that risk stratification methods for children are different and needs further validation. As we strive to achieve zero tolerance for SSI, we review data in a variety of ways to assure that potential risk factors are not overlooked.

Adjuvant weekly docetaxel (D) for high-risk prostate cancer patients (pts) after radical prostatectomy (RP): Preliminary data of a multicenter pilot trial

4649 Background: Over the past decade more PC pts are diagnosed early and treated locally. 40–60% recur after local treatment. We conducted a pilot post RP adjuvant study in pts at high risk for recurrence after RP. Study objectives were to evaluate: 1. toxicity (tox) 2. feasibility of 6 months of adjuvant D treatment and 3. Incidence of PSA relapses (>0.2ng/ml) in 2 and 3 years (vs. matched controls). Methods: Pts with confirmed PC, within 3 months of RP, and without distant metastases, organ dysfunction, RT, or systemic treatment were eligible. Pathology was centrally reviewed (JHU) and risk assessment was based on a multivariate Cox proportional hazards model (Rw' = lymph node (0/1)*1.43 + seminal vesicle (0/1)*0.51 + surgical margin (0/1)*1.15 + modified Gleason score (MGS) (0–4) * 0.71) [MGS: Gleason 5=0; 3+3=1; 3+4=2; 4+3=3; 8–10=4]. The minimum value for study entry was based on a projected 50% rate of recurrence by 3 years = Rw' > 2.84. (Roberts, et al. Urology, 2001). Treatment included I.V.D 35mg/m2 Days 1, 8, 15 of a 28-day cycle x 6 cycles starting 4–12 weeks after surgery. We have 90% power to detect a 3-year progression free survival rate of 69% versus the control rate of 50%, α=0.05. Results: 77 pts were registered (2/02–12/03). Median age: 60 (43–76). Median Rw' 4.07 (2.85–5.93). Tox in the first 51 pts. Grade IV: hyperglycemia 3.9%. Grade III: hyperglycemia 9.8%, dyspnea 5.8%, leukopenia 3.9%. 1 pt. required dose reduction (LFT's), only 2 had delay in Rx. One death unrelated to D. Grade I/II (>30%): fatigue, alopecia, nail changes, diarrhea, dyspepsia, dyspnea, flushing, hyperglycemia, insomnia, nausea and peripheral sensory neuropathy. Data on PSA progression is preliminary at this time. Conclusions: Post-operative adjuvant weekly D for high risk PC pts is feasible and has moderate reversible toxicity. Rapid accrual suggests high-level of pt and physicians interest. Additional follow up is needed for outcome assessment. (Supported by Aventis). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Aventis; Celegene AstraZeneca; Aventis; Berlex; Millenium