By: Dan Sperling, MD

Most prostate cancer (PCa) is diagnosed while it is still confined to the prostate gland, and considered amenable to local treatment. Conventional whole-gland treatments (radical prostatectomy and beam radiation) predominate the therapeutic world, with radical prostatectomy (RP) considered the gold standard. Following treatment, the standard of care is an annual PSA blood draw and digital rectal exam (DRE). Within 10 years of treatment, 35% of all patients who have a whole-gland treatment will experience biochemical recurrence demonstrated by an elevated and/or rising PSA.[i] Biochemical recurrence is also referred to as biochemical failure.

Definitions of biochemical recurrence following PCa treatment

Despite the accepted definitions of biochemical recurrence, patients are generally advised that there is room for variation. After RP, the presence of a very low PSA is not always a predictor of local, regional or distant metastasis. After radiation, if PSA begins to rise above nadir, some clinicians do not wait for the rise to reach 2 ng/mL, but encourage further testing in order to detect recurrent disease as early as possible. As with localized prostate cancer, the sooner recurrence is identified, the better the treatment plan.

Previously, imaging by ordinary MRI, CT and bone scans often missed very small recurrent lesions in the prostate itself (post-radiation), the prostate bed, lymph nodes, bone or other organs (post-RP and post-radiation). The continuing rise of PSA was a source of fear and anxiety for the patient. Today, if local recurrence is ruled out by 3T multiparametric MRI, and other explanations for the rise in PSA are eliminated, imaging by positron emission tomography (PET) scans play a key role in detecting metastatic PCa in the lymph nodes, bone, and other organs. PET scans can be acquired with either MRI or CT, as the tracers, or isotopes, used with PET show up on either type of scan (See https://sperlingprostatecenter.com/introduction-positron-emission-tomography-imaging-pet-scans/ for more information on PET.)

Two recent papers illustrate the experience of clinicians who used a specific isotope called 18F-choline in either PET/MRI or PET/CT to locate sites of early metastatic PCa. An earlier article by Dr. Sperling states:

Because prostate cancer cells are hungry for anything that will fuel their rapid growth, it is this feature that allows the tumor to be imaged. Prostate cancer eagerly takes up choline, which is a naturally occurring part of the B-vitamin complex. The tumor cells need nutrients to multiply quickly, and they use choline as a kind of building block. It collects in any prostate cancer tumors, whether located in the prostate, lymph nodes, or more remote locations. When choline is labeled with a type of radioactivity called C-11, the PET scanner picks up the exact location of the tracer concentrations. As 3-dimensional images of the target regions are processed, the tumors are shown as brightly lit spots or areas.[ii]

The first paper is from an Italian research group out of Genoa.[iii] It describes their technical study of co-registration (fusion) of imaging modalities in order to coordinate image-based navigation, and produce integrated interpretation that is not possible with separate assessments using different technologies. Their objective was to combine multiparametric MRI (mpMRI) which offers “high diagnostic accuracy in detecting local recurrence” with choline-PET/CT which can pick up lymph node and bone lesions earlier than other types of imaging. They explored the co-registration of two modes (bimodal) with choline-PET and mpMRI, and that of three modes (trimodal) by integrating real-time transrectal ultrasound (TRUS) to bimodal imaging. They wrote that bimodal imaging “…allows morphological, functional and metabolic information to be combined…” while real-time trimodal imaging “…may be useful for the planning and real-time guidance of biopsy procedures in order to obtain histological [tissue analysis] confirmation of the local recurrence.”

The second paper is from a different Italian medical research facility (Rovigo, Italy) in collaboration with radiologists from UCLA.[iv] The authors evaluated a new protocol designed to improve the clarity of pelvic PCa imaging using 18F-choline PET/CT scans. They prospectively scanned 250 PCa patients (mean age 72, mean PSA 7.9) after administering the isotope 18F-choline by intravenous injection. Each patient underwent a double-scan process in which early pelvic images (4 minutes after injection) were followed by whole-body scans at 1 hour after injection. The early and 1-hour delayed images of the pelvis were compared. They found that

• 21% of patients with positive 18F-choline demonstrated abnormal local uptake (immediate prostatic region) of the isotope. When compared with the delayed scans, the prostatic region uptake “was better visualized in the early phase in 32/57 cases.”
• 18% showed distant localization only, and the lesions “were visualized on both early and late images with similar uptakes values.”
• 38% did not show any pathological uptake

The authors concluded that while all pelvic lesions (prostate, lymph nodes, bone) were visualized in both early and late images, the early ones improved lesion clarity.

It is reassuring that choline-PET imaging can be used to identify the sites of PCa biochemical recurrence in order to maximize effective treatment planning.

[i] Bruce JY, Lang J, McNeel D, Liu G. Current controversies in the management of biochemical failure in prostate cancer. Clin Adv Hem Onc. 2012 November;10(11):716-22.

[ii] https://sperlingprostatecenter.com/choline-c-11-pet-scans-prostate-cancer/

[iii] Paparo F, Piccardo A, Bacigalupo L et al. Value of bimodal 18F-choline-PET/MRI and trimodal 18F-choline-PET/MRI/TRUS for the assessment of prostate cancer recurrence after radiation therapy and radical prostatectomy. Abdom Imaging. 2015 Jan 13. Epub ahead of print.  doi: 10.1007/s00261-014-0345-0n

[iv] Chondrogiannis S, Marzola MC, Grassetto G et al. Optimized protocol for 18F-choline PET/CT in patients with biochemically relapsed prostate cancer: Experiences on 250 consecutive cases . Clin Nucl Med. 2015 Jun;40(6):e308-12.