Multiparametric MRI (mpMRI) has proven to be of great utility in detecting and assessing the aggressiveness of localized prostate cancer (PCa). It can identify extracapsular extension into the prostate bed and seminal vesicles, which is essential for treatment planning. Another type of imaging called Positron Emission Tomography/Computer Tomography (PET/CT) can be useful in the following instances:

• Staging primary cancer to determine if it’s localized
• Detecting suspected PCa recurrence after radical prostatectomy or other treatment
• Detecting the location of metastatic prostate cancer in the lymph nodes, bone, or other organs.

When clinical factors such as a high PSA, rapidly rising PSA, or other biomarkers indicate the possibility that PCa has spread beyond the capsule, early detection of disease location and extent is an advantage in managing the cancer. However, finding advanced PCa can be a challenge if the spread is still too small to be visible on mpMRI.

PET/CT scans involve the administration of very low dose radioactive tracers that will be visible on the scan. The tracers, called isotopes, are molecularly bonded with substances that cancer cells preferentially “absorb” as fuel for their growth. These substances are usually derived from carbohydrates such as glucose, a type of sugar, but in a form that healthy cells do not take up. Thus, as cancer cells metabolize the glucose-bonded isotopes, even very small cellular changes pointing to cancer will enhance (“light up”) on PET/CT scans before they become tumors able to be seen on mpMRI. The following is a summary of two recent studies that explore the effectiveness of two specific isotopes: (18)F-flourodeoxyglucose (abbreviated as FDG) and 18F-Fluciclovine (also called anti-3-F-FACBC, abbreviated as F-FACBC).

Study on (18)F-flourodeoxyglucose

Beauregard et al. (Quebec; 2015) evaluated the use of FDG-PET/CT for pre-operative staging, and to determine how to stratify patients whose biopsy results indicate high Gleason grade.[i] The authors note that earlier studies suggest that FDG is not well taken up by low-grade or indolent PCa, whereas it seems to be well taken up by aggressive cancer lines. Their earlier work revealed that with high-grade PCa (Gleason > 8) FDG-PET/CT had a cancer detection rate of 69% vs. 13% for conventional CT and bone scan. Therefore, they recruited 54 patients with Gleason > 8 PCa who underwent FDG-PET/CT scanning during their staging protocol. Thirty-nine of them had radical prostatectomy (RP) with pelvic lymph node dissection for lab analysis; two patients had lymph node dissection only, and 13 had non-surgical treatments (androgen deprivation alone or with radiation therapy). Three radiological readers, blinded to pre-treatment clinical factors and the histopathology results of gland and lymph node specimens, interpreted the FDG-PET/CT scan results and assigned numeric values (from 0 to 4, 0 indicating no suspicion of PCa and 4 being very intense level of suspicion). Imaging results were compared with clinical factors and histopathology results.

The authors report that imaging showed increased FDG uptake (suspicion of cancer) in the prostate for 44% of patients, in the lymph nodes for 13% of patients, and in the bone for 9% of patients. There was a significant correlation of prostatic FDG with higher clinical stage, post-RP Gleason score, and the volume of cancer within the prostate. 84.6% of patients whose imaging showed no FDG uptake within the prostate were subsequently downgraded to Gleason ?7 after RP histopathology findings were complete. As far as prognosis, the absence of FDG uptake in the prostate was associated with a median 5-year cancer free survival probability, whereas the presence of uptake was calculated to predict 26.9% chance of cancer free survival at 5 years. The study led the team to conclude, “These results suggest that, among patients with a high-grade PCa at biopsy, FDG-PET/CT could improve pre-treatment prognostic stratification by predicting primary PCa pathological grade and survival probability following RP.”

Study on 18F-Fluciclovine (F-FACBC)

Nanni et al. (Italy; 2015) designed a study to compare how well F-FACBC PET/CT would detect recurrence of prostate cancer compared with another isotope called 11C-Choline, also used in PET/CT scans to detect PCa.[ii] Suspicion of recurrence was identified by rising PSA blood test values. Because there was scant data comparing the promising F-FACBC vs. the more established 11C-Choline, it was the goal of the authors to obtain a more definitive comparison between the two.

The team prospectively enrolled 50 patients who had previously undergone radical treatment for their PCa, and who were now experiencing rising PSA. The patients were not using hormone ablation at the time of the scans, and had both types of scans within a period of a week. Results were compared “in terms of “detection rate on a patient and lesion basis. Furthermore, a more detailed analysis regarding local, lymph node, and bone relapse was performed.” In all areas, F-fluciclovine proved to be significantly better than C-choline. In addition, F-fluciclovine demonstrated superior detection rates for low, intermediate and high PSA levels. While these results appear to affirm better performance in detecting lesions by F-FACBC, the authors recommend more studies to validate their results.

Conclusion

As imaging continues to evolve and improve, the noninvasive assessment of location, extent and aggressiveness of disease will mean earlier, more comfortable PCa detection of local, regional and distant disease, affording patients better treatment planning. As clinical research and development proceeds, the complementary use of biomarkers will round out the information gained through imaging. Progress in investigative immunotherapies that can be administered as soon as advanced disease is diagnosed offers hope of cure to future patients with metastatic prostate cancer.

[i]Beauregard JM, Blouin AC, Fradet V, et al. FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade prostate cancer at biopsy. Cancer Imaging. 2015 Mar 3;15:2. doi: 10.1186/s40644-015-0038-0. Free article at http://www.cancerimagingjournal.com/content/15/1/2

[ii] Nanni C, Schiavina R, Brunocilla E et al. 18F-Fluciclovine PET/CT for the Detection of Prostate Cancer Relapse: A Comparison to 11C-Choline PET/CT. Clin Nucl Med. 2015 Aug;40(8):e386-91. doi: 10.1097/RLU.0000000000000849.