SIU 2018: PET and Fluorescence Imaging for Recurrent/Advanced Prostate Cancer

Seoul, South-Korea (UroToday.com) PET imaging has become a staple of recurrent and advanced prostate cancer, with technology rapidly progressing – and evidence having difficulty keeping up. In this talk, Dr. Miki briefly reviews PET imaging and fluorescence technology. He went through a lot of data very quickly, but below, I highlight the take-away points from his talk. As we all know, the current standards for prostate imaging and staging (CT Abdomen/Pelvis and NM Bone scan) have very low sensitivities (especially at low PSA levels) and therefore may not detect disease until it is very advanced. PET/CT (combination with CT scans) have begun to fill in that need and bridge the gap. 

PET/CT imaging for prostate cancer comes in many flavors, depending on the radiotracer used.
1. FDG – based on glucose metabolism, it has been around the longest. However, its utility in prostate cancer is limited as PCa is not glucose metabolism dependent
2. Choline – an essential component of cell membrane phospholipids which is overexpressed in prostate cancer. It is useful in providing information on the presence of nodal metastases, however its detection of small nodal mets and micrometastases is limited
3. PSMA – highly specific for prostate cancer (also found in the parotid gland, colon, duodenum, thyroid cancer, lung cancer, etc.), it has been the most promising of the recent ligands due to its specificity. As such, it has a much higher detection rate at smaller volume disease
  • Particularly effective over other PET modalities and traditional imaging in the PSA 1-2 range (76% sensitivity) – decreases as the PSA decreases <1.0 (but still not bad!).
  • It also picks up 50% of lymph nodes > 3.7 mm, and 90% of lymph nodes > 6 mm
Current guidelines recommend PET imaging for restaging after biochemically recurrent prostate cancer – but NOT for initial staging, though certain centers and countries are doing this already. 

Theranostics – combination of therapy and diagnostics. In the setting of PET imaging, this involves combining heavier radionuclides with the tracer (radioligand therapy, RLT). Therapeutic agent tagged to the tracer enabling increased specificity in delivery. 
  • These heavier therapeutic agents include Lutetium, Yttrium, and Indium
  • There is promising clinical data for each of these, he briefly presented the data out of Heidelberg regarding Lutetium
  • However, at this time, all of this is done under clinical trial
He next shifted gears to fluorescence imaging with a focus on pelvic lymph node dissection (PLND) for prostate cancer. There has been lots of studies looking at the impact of extent of PLND (limited, extended, super-extended) on prostate cancer outcomes, including BCR-free survival and disease-specific survival. 
  • We know that increasing the extent of PLND results in greater nodes removed and a higher percentage of % LN’s
  • NCCN and EAU guidelines recommend ePLND for high-risk PCa
  • However, Fossati et al. (EU 2017) demonstrated on systematic review that ePLND was associated with higher complications but not necessarily improved survival
  • There are currently 2 prospective international trials ongoing looking at impact of LND extent
The concept of sentinel lymph node dissection (SLND) is a carryover from the breast cancer literature, where it is routinely used in axillary node dissections. The sentinel node (SLN) represents the first LN cancer drains to. While this is standard of care in breast cancer, the evidence is lacking in prostate cancer. However, Dr. Miki’s, amongst others, has been working to explore its role in PCa management.

A systematic review by Wit EMK et al. (EU) of 2509 patients found that SLND had high sensitivity (95%) and specificity (100%), but a false negative rate of 5%. At a consensus pane in Berlin in 2016, the recommendation was that ePLND was still the gold standard, but SLND should be combined with ePLND – as the consensus on tracer technology was insufficient.

Intraoperative SLND can be done with:
1.Gamma-ray detection probe
2. Gamma camera
3. Fluorescence camera with indocyanine green (ICG) – this is what Dr. Miki works with
4. Navigation

He presented some of his work (Miki et al. The Prostate 2017) looking at the use of ICG fluorescence in 50 men undergoing radical prostatectomy. In the study, interestingly, they found 3 distinct drainage patterns for tumors – and traditional nodal packets did not adequately capture all 3.

Frequency of lymphatic patterns
In this study, 91% of positive lymph nodes were in the sentinel lymph node. Other studies have also demonstrated high sensitivity for SLND using ICG fluorescence. 

In a study by Grivas N et al. (JNM 2018), in a study on 920 patients undergoing RALP between 2006-2016, patients underwent ePLND with or without SLND. They found that adding SLND to ePLND improved BCR-free survival. 

In a prospective study by Harke et al. (World J Urol 2018) of 120 high-risk PCa patients undergoing ePLND, patients were randomized either SLND or no SLND. The sensitivity of SLND was 78%. They deemed SLND alone to be insufficient. 

As such, as the evidence stands today, SLND may help improve patient staging and nodal yield during ePLND – but further work is needed prior to using it in isolation. 

Presented By: Jun Miki, Japan

References:
1. Wit EMK et al. EU.
2. Miki et al. The Prostate 2017.
3. Grivas N et al. JNM 2018.
4. Harke et al. World J Urol 2018.

Written By: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University Twitter: @tchandra_uromd, @TjuUrology at the 38th Congress of the Society of International Urology - October 4- 7, 2018 - Seoul, South Korea
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