Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence

In the United States, aside from nonlethal skin cancers, prostate cancer is the most common cancer among men and is the second leading cause of cancer death.1 In 2014, prostate cancer will be newly diagnosed in approximately 233,000 men.1 Three quarters of these patients will choose potentially curative surgery or radiation therapy; unfortunately, up to 40% of those treated with curative intent will experience recurrent disease.2 Accurately identifying sites of recurrence is important in making treatment decisions to achieve remission or amelioration of the disease.3 The primary difficulty in locating recurrent sites lies within the limitations of standard imaging modalities such as bone and CT scans.4,5 However, newer PET radiopharmaceuticals, such as 11Carbon (11C) acetate, 11C-choline, and 18Fluorine (18F) choline, have shown efficacy for imaging recurrent prostate cancer, demonstrating superiority over 18FDG PET/CT attenuation correction (CTAC) (PET/CTAC) and 111In capromab SPECT.6–8 Rapidly proliferating prostate cancer cells use acetate and choline as substrates in building bilipid cell membranes. By transforming these substrates into radiochemicals through the incorporation of 11C and 18F, respectively, they become imaging markers of tissue sites undergoing rapid cell membrane synthesis (Figs. ​(Figs.11 and ​and22).9,10 Since questions remain about the ability of these 2 agents to distinguish between malignant and inflammatory tissue within an intact prostate gland, their best application lies in the detection of prostate cancer after recurrence or in detecting extraprostatic spread before surgery.11,12 A number of recent studies have provided powerful evidence that there is a significant survival benefit to using these new PET scans to target salvage therapy.13,14 FIGURE 1 11C-acetate PET scan, CTAC, and fusion images of a 54-year-old patient with prostate cancer treated 6 months prior with robotic radical prostatectomy who experienced persistent elevation of his PSA of 4.6 ng/mL after surgery. Crosshairs show a 1.4-cm ... FIGURE 2 11C-acetate PET scan, CTAC, and fusion images of a 59-year-old patient with prostate cancer treated 5 years prior with brachytherapy who presented with a prescan PSA of 0.4 ng/mL. Crosshairs show a 0.6 × 1.4-cm pelvic node anteromedial to the ... Although the effectiveness of 11C-acetate, 11C-choline, and 18F-choline PET/CTAC is well supported for recurrent disease, there is reduced sensitivity when scanning patients with prostate-specific antigen (PSA) values less than 1 ng/mL.15 On the other hand, studies examining progression rates for patients receiving salvage radiotherapy for biochemical recurrence after prostatectomy show no significant difference between the progression rates for patients with preradiotherapy PSA levels ≤ 1.0 ng/mL and patients with preradiotherapy PSA levels > 1.0 but ≤ 2.0 ng/mL. Patients with PSA levels of ≤ 2.0 ng/mL had a 4-year progression-free probability (PFP) of 77% if there were no adverse features. Those with PSA levels ≤ 2.0 ng/mL but with rapid PSA doubling times (PSADT) had 4-year PFPs of 64% and 22% when the surgical margins were negative and positive, respectively. Patients with pretreatment PSA levels greater than 2.0 ng/mL had 4-year PFPs of 20%, regardless of PSADT, surgical margin status, or Gleason score.16,17 Therefore, our aim was to identify which patients’ characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/CTAC imaging of recurrent prostate cancer, ideally at a PSA level low enough to preserve the greatest PFP if salvage therapy is undertaken.