THE "NEW" PROSTATE CANCER INFOLINK

Two papers presented at the meeting on Monday this week addressed radical prostatectomy in high risk patients and different applications of androgen deprivation therapy for their impact on overall patient survival, using the Johns Hopkins patient database as their starting point.

Schaeffer et al. (abstract no. 763) have evaluated the long-term survival of 175 men diagnosed with high-risk prostate cancer and treated with radical prostatectomy at Johns Hopkins by a single surgeon between 1992 and 2008. All 175 patients met the D’Amico criteria for high-risk disease (clinical stage >T2c, biopsy Gleason score 8 to 10, or PSA >20 ng/ml). In this population the rates and predictors of biochemical progression, metastatic disease and cancer-specific mortality were evaluated. The median patient age was 59 years, and median follow-up was 8 years. A subset analysis of the D’Amico high-risk criteriashowed that 63/175 men (36 percent) had a biopsy Gleason score of 8 to 10; 66 (38 percent) had a clinical stage of  > T2c, and 58 (33 percent) had a preoperative PSA level > 20 ng/ml.  (Six percent of the patients had more than one high risk factor). At radical prostatectomy, 63 (36 percent) had organ-confined disease, whereas extracapsular extension and seminal vesicle invasion were present in 79 (45 percent) and 8 (5 percent), respectively. Positive surgical margins were reported in 32 (18 percent) and lymph node metastases in 25 (14 percent). At 10 years, biochemical recurrence-free survival was 68 percent, metastasis-free survival was 84 percent, and prostate cancer-specific survival was 92 percent. In addition, the 10-year rate of freedom from any hormonal therapy was 71 percent (although it should be rememebred that Johns Hopkins discourages the use of hormone therapy until there are clear signs and symptoms of the need for palliative care). Of the high-risk criteria, a biopsy Gleason score of 8-10 (vs. <7) was the strongest independent predictor of all outcomes, with hazard ratio and p-value of 3.17 (p = 0.027), 4.19 (p = 0.015), and 6.57 (p = 0.011) for biochemical recurrence, metastases, and prostate cancer death, respectively.This paper certainly suggests that surgery is a highly appropriate form of care for some carefully-selected men with high-risk prostate cancer.

Trock et al. (abstract no. 1285) have assessed the survival benefit of androgen deprivation therapy used as immediate salvage therapy after biochemical recurrence in the Hopkins database. As noted above, it has generally been Johns Hopkins position that hormonal therapy should be delayed until there are clear signs or symptoms of progressive disease. The authors studied overall survival (OS) among 488 men who udnerwent radical prostatectomy between 1982 and 2004 and who then were treated with androgen deprivation therapy (without radiation) vs. no therapy on biochemical recurrence. With a median follow-up of 6 years after biochemical recurrence and 9 years after radical prostatectomy, there were 143 deaths overall,  including 104 prostate cancer deaths. Men who received immediate ADT on biochemical recurrence were more likely to have a pathologic Gleason score of 8-10 and seminal vesicle and lymph node involvement. In a multivariable model adjusted for PSA doubling time, pathologic stage, pathologic Gleason score, time from surgery to biochemical recurrence, and year of radical prostatectomy, immediate ADT strongly improved OS in men with a PSA coubling time of < 6 months (hazard ratio [HR] = 0.27, p = 0.003). Men with a PSA doubling time of < 6 months comprised 28 percent of the study sample. In contrast, immediate ADT did not improve OS in men with a PSA doubling time of >6 months (HR = 1.53, p = 0.140).The authors concluded that immediate ADT (which they refer to as “salvage androgen deprivation” or SAD) provides an important increase in OS for men with post-surgical biochemical recurrence who have a PSA doubling time of < 6 months, regardless of other adverse prognostic features.