Adam Lam

Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate Cancer

PURPOSE We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen (PSA), or histologic progression as treatment indications for clinically localized prostate cancer. PATIENTS AND METHODS This was a prospective, single-arm, cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data. Results A total of 450 patients have been observed with active surveillance. Median follow-up was 6.8 years (range, 1 to 13 years). Overall survival was 78.6%. The 10-year prostate cancer actuarial survival was 97.2%. Overall, 30% of patients have been reclassified as higher risk and have been offered definitive therapy. Of 117 patients treated radically, the PSA failure rate was 50%, which was 13% of the total cohort. PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years (P < .0001). The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years. CONCLUSION We observed a low rate of prostate cancer mortality. Among the patients who were reclassified as higher risk and who were treated, PSA failure was relatively common. Other-cause mortality accounted for almost all of the deaths. Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis.

Comparing Prostate Specific Antigen Triggers for Intervention in Men With Stable Prostate Cancer on Active Surveillance

PURPOSE We determined the proportion of men with nonprogressive prostate cancer on active surveillance who had a trigger for treatment using various measures of prostate specific antigen kinetics. MATERIALS AND METHODS A prospective phase II study of patients with favorable clinical parameters (stage T1b-T2b N0M0, Gleason sum 7 or less, prostate specific antigen 15 ng/ml or less) on active surveillance was initiated in 1995. Those patients considered at high risk for progression were offered radical intervention. The remaining patients were closely monitored and formed the cohort for this study. We calculated the proportion and frequency of patients who had a trigger for treatment based on the various prostate specific antigen triggers (prostate specific antigen doubling time, prostate specific antigen velocity, prostate specific antigen threshold). RESULTS Of 450 patients followed on surveillance 305 remained on active surveillance without definitive intervention. None of these 305 patients have died of prostate cancer or have had symptomatic metastatic disease develop. Median followup was 6.8 years. The proportion of patients who would have had a trigger for treatment ranged from 14% to 42% for the threshold triggers, 37% to 50% for the prostate specific antigen doubling time triggers and 42% to 84% for the velocity triggers. CONCLUSIONS Almost all of the prostate specific antigen triggers examined in this study would have led to high rates of trigger for treatment. More work is needed to identify a trigger that better strikes the balance between recommending treatment for patients at high risk for progression and minimizing treatment for those at low risk for progression.

Initial transfusion intensity predicts survival in myelodysplastic syndrome

Abstract We evaluated 52 patients with myelodysplastic syndrome (MDS) who had received at least one red blood cell (RBC) transfusion. In the 4-week period following the first transfusion, 24 patients (group 1) required no transfusion, while 28 (group 2) required transfusion of two or more units of RBCs. Survival was greater in group 1 (440 weeks vs. 167 weeks, p < 0.01), even when only international prognostic scoring system (IPSS) low and intermediate-1 risk patients were analyzed (median overall survival 491 vs. 170 weeks, p < 0.05), independent of age, IPSS and progression to acute myeloid leukemia (AML). The intensity of transfusion required in the first few weeks after the first transfusion predicts disease severity and correlates with survival.