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Purpose We assessed outcomes of men with prostate cancer enrolled in active surveillance. Patients and Methods Since 1995, a total of 769 men diagnosed with prostate cancer have been followed prospectively (median follow-up, 2.7 years; range, 0.01 to 15.0 years) on active surveillance. Enrollment criteria were for very-low-risk cancers, defined by clinical stage (T1c), prostate-specific antigen density < 0.15 ng/mL, and prostate biopsy findings (Gleason score ≤ 6, two or fewer cores with cancer, and ≤ 50% cancer involvement of any core). Curative intervention was recommended on disease reclassification on the basis of biopsy criteria. The primary outcome was survival free of intervention, and secondary outcomes were rates of disease reclassification and exit from the program. Outcomes were compared between men who did and did not meet very-low-risk criteria. Results The median survival free of intervention was 6.5 years (range, 0.0 to 15.0 years) after diagnosis, and the proportions of men remaining free of intervention after 2, 5, and 10 years of follow-up were 81%, 59%, and 41%, respectively. Overall, 255 men (33.2%) underwent intervention at a median of 2.2 years (range, 0.6 to 10.2 years) after diagnosis; 188 men (73.7%) underwent intervention on the basis of disease reclassification on biopsy. The proportions of men who underwent curative intervention (P = .026) or had biopsy reclassification (P < .001) were significantly lower in men who met enrollment criteria than in those who did not. There were no prostate cancer deaths. Conclusion For carefully selected men, active surveillance with curative intent appears to be a safe alternative to immediate intervention. Limiting surveillance to very-low-risk patients may reduce the frequency of adverse outcomes.

Purpose Among patients with biochemical recurrence after radical prostatectomy, we found previously that postoperative prostate-specific antigen doubling time (PSADT) was associated with risk of prostate cancer death. However, given the small number of patients in the highest risk PSADT subgroup, it is unclear which PSADT subgroups contribute the greatest to prostate cancer–specific death and how this influences all-cause mortality. Patients and Methods This study was a retrospective analysis of 379 patients treated with radical prostatectomy between 1982 and 2000 who had a biochemical recurrence and PSADT data available. Mean and median follow-up after surgery was 11.4 (standard deviation, 5.4) and 11.0 years, respectively (range, 1.6 to 23.0 years). Results Shorter PSADT was significantly associated with prostate cancer–specific and all-cause mortality (P < .001). Although patients with a PSADT less than 3 months were at the greatest risk of death, because of the limited number of patients in this group, they accounted for only 13% of prostate cancer deaths at 15 years after biochemical recurrence, whereas patients with an intermediate PSADT (3.0 to 8.9 months) accounted for 58% of all prostate cancer deaths. Among patients with a PSADT less than 15 months, prostate cancer accounted for 90% of all deaths. Only patients in the slowest PSADT subgroup (≥ 15 months) had a greater risk of competing-causes mortality compared with that from prostate cancer. Conclusion Among a select cohort of young, healthy patients with PSA recurrence after radical prostatectomy and a PSADT less than 15 months, prostate cancer accounted for an estimated 90% of all deaths by 15 years after recurrence. The majority of prostate cancer deaths occurred among patients with an intermediate PSADT (3.0 to 8.9 months).

5020 Background: The importance of local treatment in oligometastatic prostate cancer (OPC) is unknown. Stereotactic ablative radiotherapy (SABR) is highly focused, high-dose radiation that is well suited for treatment of oligometastases. Here we report on the safety and preliminary clinical outcomes of SABR in a modern cohort of OPC men. Methods: Eighty four men who satisfied criteria of OPC diagnosed on imaging underwent consolidative SABR were then followed prospectively on our IRB approved registry by our GU multidisciplinary team. We collected demographic, clinical, toxicity and efficacy information. We examined the first 66 men in this preliminary report to allow for a minimum of 4.5 months follow-up. SABR was delivered in 1-5 fractions of 5-18 Gy. Kaplan-Meier method was used to assess local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir+2), distant progression free survival (DPFS), ADT-free survival (ADT-FS) and time-to-next intervention (TTNI). Results: Of the 66 OPC patients analyzed, 25 (38%) men presented as synchronous OPC and the remaining 41 had recurrent OPC. Median and mean follow-up was 61 and 66 weeks, respectively. Patient and disease factors as listed in the Table. Crude Grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no Grade > 2 toxicity. SABR was delivered to 134 metastases: 89 bone (66%), 40 nodal (30%) and 5 (4%) visceral metastases. Overall LPFS at 1-year was 92%. The bPFS and DPFS at 1-year were 69% and 69%, respectively. Median TTNI was not reached yet. Of the 18 men with hormone sensitive prostate cancer who had their ADT deferred, 11/18 (56%) remain free of disease following SABR (1-year ADT-FS was 78%) and in 17 castration resistant men, 11 had > 50% PSA declines with 1-year TTNI of 30% with a median of 45 weeks. Conclusions: Consolidative SABRfor OPCis feasible and well tolerated. The preliminary clinical outcomes in our series is limited by heterogeneity and size but our data suggests that this approach is worthy of further prospective study. [Table: see text]

5036 Background: Active surveillance for low risk disease has been gaining acceptance with the aim of preferentially treating men with NCCN intermediate and high risk prostate cancer. Currently used outcome estimates however, were developed using cohorts, which included a high proportion of men with low or very low- risk disease. Here we describe the natural history of intermediate and high-risk prostate cancer treated only by radical prostatectomy (RP). Methods: Men who underwent RP in the PSA era, initially had undetectable PSAs after surgery, and received no post-RP therapy prior to metastasis were included (1,739 men). Biochemical recurrence (BCR) was defined by a PSA of ≥0.2 ng/ml and metastasis was diagnosed by axial imaging or bone scan. Results: Median follow up was 10 years and 17% developed BCR with a median time to BCR of 3 years (range 1-18). Of men with BCR, 41% developed metastasis (median time 3 years (range 0-11) after BCR). Median time from metastasis to death was 4 years (range 0-11). Me...

179 Background: Biochemical recurrence (BCR) most frequently occurs within the first five years following radical prostatectomy. Prior studies have suggested an association between lower-risk disease features and BCR at 5 years postoperatively. The objective of our study was to determine predictors of BCR ≥10 years after radical prostatectomy, and to examine the relationship between timing of BCR with the subsequent risk of metastases and cancer-specific mortality. Methods: Among 10,609 men from our institutional radical prostatectomy database, we identified 1684 men with BCR (PSA >0.2 ng/ml) without prior hormonal or radiation therapy. These men were classified into by the time of BCR: early (10 years). Univariable and multivariable models were used to examine the association of clinico-pathologic variables with the timing of BCR. We also examined metastasis-free and cancer-specific survival based upon the timing of BCR. Results: Of BCR, 77.0%, 16.6%, 4.9%, and 1.5% occurred at 15 years postoperatively. Late recurrences were associated with more favorable pathologic features, and were unlikely to develop metastases or prostate cancer-specific mortality. Conclusions: The majority of BCR occurs within 10 years of surgery. Although 6.4% of BCR occurred at ≥10 years, these patients were unlikely to subsequently develop metastases or die from prostate cancer. Patients who remain free from progression at 10 years postoperatively should be counseled that their risk of subsequent cancer-related morbidity and mortality is low. No significant financial relationships to disclose.

siderations that strongly influence the decision about the use of 5--reductase inhibitors (5-ARIs) for the chemoprevention of prostate cancer. First, 5-ARIs do not prevent prostate cancer, they just prevent men from undergoing diagnostic biopsies. Because 5-ARIs reduce prostate-specific antigen (PSA) levels by at least 50%, patients and their physicians can be lulled into a false sense of security. In the first sevenyearsoftheProstateCancerPreventionTrial(PCPT),although 25% fewer men on finasteride were diagnosed with prostate cancer, this occurred largely because 15% fewer men underwent a diagnostic biopsy.Inthemenonfinasteridewhoactuallyunderwentabiopsy,the risk of a positive biopsy was reduced by only 10% (biopsies were positive in 26.5% of men on finasteride and in 29.5% of men on placebo; a 3% absolute difference which was not statistically significant [95% CI, 0.81 to 1.0]). 2 Thus,finasteride will have no significant effect on reducing the risk of cancer in men who are followed closely and undergo a biopsy because of an elevated PSA or abnormal digital rectal examination, which is the exact setting where it would be used for prevention. For the patient who watched his father die from pros

5007 Background: Nomograms that predict prostate-specific antigen (PSA) defined biochemical recurrence (BCR) of prostate cancer after radical prostatectomy are the most widely used prediction tools in oncology for treatment decision making and counseling. While BCR universally antedates prostate cancer-specific mortality (PCSM), it is a limited surrogate endpoint due to its variable natural history. Nomograms that accurately predict the risk of PCSM are needed. Methods: Using Fine and Gray competing risk regression analysis, the clinical data and follow-up information of 11,521 patients treated with radical prostatectomy at four academic centers from 1987 to 2005 were modeled to predict PCSM. The model was externally validated on 12,893 patients treated at a separate institution during the same period. Results: The 15-year PCSM and all-cause mortality was 7% and 33%, respectively. The 15-year PCSM for patients with final pathological Gleason score 2–6, 3+4, 4+3, and 8–10 was 1%, 7%, 8%, and 49%, respectively. By pathologic stage, the risks were 2%, 7%, 29%, and 23% for organ-confined, extraprostatic extension, seminal vesicle invasion, and lymph node-positive prostate cancer. Of 3756 patients with organ-confined and Gleason 2–6 cancer, only 1 (0.03%) died from prostate cancer. Primary and secondary Gleason grade (p < 0.001 for both), seminal vesicle invasion (p < 0.001), and year of surgery (p = 0.002) were significant predictors of PCSM. A nomogram predicting 15-year PCSM based on pathologic parameters was accurate and discriminating with an externally-validated concordance index of 0.92. Conclusions: A nomogram has been constructed that predicts the long-term risk of PCSM after radical prostatectomy based on the pathologic grade and stage of the cancer. The presence of poorly differentiated cancer and seminal vesicle invasion are the prime determinants of PCSM. Our study suggests that biomarkers may have limited empiric prognostic utility as PCSM can be accurately predicted once the pathologic features of prostate cancer are known. No significant financial relationships to disclose.

5065 Background: Early hormonal therapy has been used in the salvage setting for men with biochemical recurrence following radical prostatectomy (RP), but no studies to date have been able to evaluate whether such treatment prolongs survival. We examined the impact of salvage hormonal therapy on overall survival (OS) in a cohort with long-term follow-up, and attempted to identify the subgroup most likely to benefit. Methods: Retrospective analysis of a cohort of 488 men undergoing RP at Johns Hopkins Hospital from 1982–2004, who experienced biochemical recurrence and received no salvage therapy (n = 386) or salvage hormonal therapy (n = 102); no one received adjuvant therapy. Survival was defined from biochemical recurrence to death from all causes, and analyzed with proportional hazards models with time-dependent covariates. Results: With median follow-up of 6 years after recurrence and 9 years after RP, there were 143 deaths (29%), including 105 from prostate cancer. After adjusting for PSA doubling time (PSADT), RP Gleason score, and year of surgery, hormonal therapy did not significantly improve OS for all men, compared to no salvage therapy: hazard ratio (HR) = 0.72 (95% confidence interval (CI): 0.45–1.17), p = 0.187. However, when restricted to men with early recurrence, i.e. within 2 years of RP, and with a rapid PSADT6 months: HR = 1.96 (95% CI: 0.89–4.31), p = 0.093, nor those who recurred more than 2 years after RP, regardless of PSADT. Conclusions: This study suggests that early salvage hormonal therapy may significantly and substantially prolong overall survival in the subgroup of men who experience an early biochemical recurrence with a rapid PSADT. These results are consistent with early recurrences being indicative of metastatic disease, while later recurrences are more likely to represent local recurrence. If validated, these results may provide useful stratification criteria for clinical trials. No significant financial relationships to disclose.

4571 Background: For men developing PSA failure after radical prostatectomy (RP), administration of immediate androgen deprivation therapy (ADT) has not been shown to improve survival compared to delaying ADT until evidence of metastatic disease. We evaluated factors influencing prostate cancer (PCa) specific mortality (PCSM) in a cohort of PSA era patients developing metastases after RP treated with delayed ADT. Methods: 3,658 men had RP by a single surgeon at Johns Hopkins Hospital from 4/82 until 6/05. 553 had PSA failure. 216 developed radiographically evident distant metastasis. Of these, 91 men formed the study cohort: initially treated during the PSA era (1987–2005), received ADT only after documented metastasis, and having complete data. 41 of these men died. Median failure times were estimated with the Kaplan-Meier method. Prognostic impact was estimated as the hazard ratio (HR) derived from the Cox proportional hazards model. Results: Median followup from RP was 10 yrs (range 2–18). Actuarial median failure times are: 1 yr from RP to PSA failure (range 1–11), 32 mos from PSA failure to metastasis (range 0–129), 79 mos from metastasis to death (range 7–181), and 13 yrs from RP to death (range 2–18). The following variables were significant prognostic factors for PCSM in univariate analyses: Pain at diagnosis of metastases (p < 0.01), time from RP to metastasis (p = 0.02), hematocrit at metastasis (p < 0.01) and PSADT No significant financial relationships to disclose.

4546 Background: The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) can be long, but variable. Better predictive models are needed to identify men early who are at...

4555 Background: Patients (pts) with biochemical (PSA) relapse after RP represent a rapidly rising population in whom appropriate standards of care remain undefined. Over the past several years we have focused on studying the natural history of these pts. Our previous report (Pound et al; JAMA 1999) suggests that the Gleason score, time of PSA relapse (>0.2 ng/ml) and PSADT are the strongest predictors of the probability of distant metastasis (DM) (Cox model). A recent update (Partin; AUA 2003, Eisenberger; ASCO 2003) suggests that PSADT overrides the other parameters in the prediction of DM. Our experience has been expanded (> 1000 additional pts and longer follow-up). We evaluate the relationship between PSADT and PCSS. Methods: 4,415 pts underwent a RP from 1982–2003 and 825 demonstrated evidence of PSA relapse. All pts were followed with yearly PSAs with no androgen deprivation given until development of DM. Cox-proportional hazards and Kaplan-Meier survival analyses were completed with time from PSA ...