The standard of care for detecting positive LNs is a pelvic CT scan with contrast. (Sometimes MRIs are used for this with no advantage other than billing for the hospital.) This is often done the same day as a bone scan for high risk patients. The CT detects the size of LNs, and suspicion of cancer is as follows:
- < 8 mm: not suspicious
- 8-11 mm: gray area
- ≥ 12 mm: suspicious
Patients with fewer and smaller positive LNs have longer survival, so if the patient wants treatment for N1 prostate cancer, whether local or systemic therapy, it is best to use an alternative method of detection.
Ultra-small paramagnetic iron oxide (USPIO) particles accumulate in healthy LNs more than in cancerous LNs. The particles and their lack can be detected in LNs using MRI. Combidex (ferumoxtran) is a brand of USPIO that is now available for this purpose, but only at Radboud University in Nijmegen, The Netherlands. It can detect positive LNs with a diameter as small as 2 mm in some cases (see this link). It is better than a C-11 Choline PET scan, which has a size limit of 6 mm. Patients wishing to engage in medical tourism to get this scan should contact Jelle Barentsz.
PET/CT or PET/MRI
As we've seen, the currently best PET scan is the DCFPyL PET/CT, which is available at Johns Hopkins and soon will be entering widespread clinical trials in the US and Canada. Tumor to background ratios may be especially better than the Ga-68-PSMA PET/CT scans now becoming available in clinical trials. DCFPyL detected 30% more positive LNs in the same patients. The Axumin (fluciclovine) PET/CT may be less accurate (see this link), but has the advantage of FDA approval, which may mean insurance/Medicare may cover its cost. PET/MRIs, now available at a handful of US institutions will provide greater accuracy. Detection of small metastases (< 2mm) is unproven even in the best of these scans.
Meredith et al. reported on 532 patients diagnosed with the Ga-68-PSMA PET/CT after PSA recurrence following initial treatment with prostatectomy (425 patients) or RT (107 patients).
- Among those treated with primary prostatectomy, positive lymph nodes were detected in 68%.
- Among those treated with primary RT, positive lymph nodes were detected in 40%.
(Update 11/14/17) Schmidt-Hegemann et al. reported on 129 patients diagnosed with the Ga-68-PSMA PET/CT:
- 20 patients were scanned before initial RT treatment
- 49 patients were scanned after PSA recurrence after prostatectomy
- 60 patients were scanned after PSA persistence after prostatectomy (PSA never became undetectable)
Positive pelvic lymph nodes were detected in:
- None in the pre-initial treatment group
- 16% in the PSA-recurrent group
- 33% in the PSA-persistent group
- Detection rates were about the same in patients with PSA< 0.05 ng/ml
Multiparametric MRI (mpMRI)
Multiparametric MRI is more specific than CT, but is no more sensitive at detecting positive LNs. In one study, only 57% were correctly staged with a DW-MRI.
Surgical pelvic lymph node dissection (PLND)
Surgical removal, or PLND, is usually performed at the same time as a prostatectomy. The surgeon looks for about 5-10 PLNs and removes them for pathological analysis. In the US, this isn't done routinely by most surgeons because it is usually negative (only about 5% of prostate cancer patients have PLN invasion when first diagnosed), there are often false negatives, and there are risks of lymphocele and lymphedema from it. There are two indicators that it may be advisable to perform a PLND:
- Risk of PLN invasion is greater than 2% (or 2.6%) on a validated nomogram like this one based on PSA, Gleason score and stage, or,
- Enlarged PLNs have been detected with CT or MRI
Even the most thorough ePLND misses positive PLNs. In one recent study, almost a quarter of positive LNs would have been missed even if ePLND had been used. Metastases don't just stick in sentinel LNs (the first ones that drain from the prostate). This is unlike breast cancer, for example. Cancer may accumulate in a LN without being detectable in all the LNs upstream from it.
The definition of the PLN field of whole pelvic radiation as defined by a consensus of radiation oncologists missed 44% of the positive LNs, in this study. A study of LN failures after whole pelvic radiation therapy found that more than half had a failure above the treated area.
Clearly, there is no imaging modality that will find all metastatic cells in the PLN area. Failure of either ePLND or whole pelvic radiation to adequately treat the pelvic LNs that are most likely to be positive is problematic. As the coverage/dissection area expands, so does the risk of side effects. Lymphedema and lymphocele may result from ePLND. Late-term damage to the upper bowel is a risk of increasing the radiation field (see this link).
Such risks must be balanced against the evidence for benefits of treatment. The success of pelvic radiation in various settings was discussed here, and early results from the STAMPEDE clinical trial among N1 patients are encouraging.