A Mayo Clinic study sought to determine exactly where the recurrences were after failure of radical prostatectomy.
Parker et al. studied recurrences in 41 patients who received a post-prostatectomy [11C]choline PET/CT scan between 2008 and 2015, and at least one recurrence site was identified (median = 2). They were all candidates for whole pelvic field salvage radiation, using at least 45 Gy of external beam radiation. The authors classified the patients’ recurrence sites as:
- IF (in-field) if the recurrence site would receive at least 45 Gy
- EOF (edge of field) if the recurrence site would receive less than 45 Gy (inadequate dose)
- OOF (out of field) if the recurrence site would not receive any radiation
They identified 121 recurrence sites. A sizeable minority (43 percent) of the recurrence sites were within the whole pelvic radiation field; however, when they looked at how many of the patients were adequately treated for all their recurrence sites, a disturbing picture emerges:
- Only 12 percent had IF recurrences
- 24 percent had EOF recurrences (median dose = 10 Gy)
- 88 percent had OOF recurrences.
- 15 percent had both EOF and OOF recurrences.
- 10 percent had both IF and OOF recurrences.
It should be mentioned that the patients did not receive the PET/CT scans until their PSA reached a median of 3.1 ng/ml ([11C]choline PET/CT scanning isn’t much good at PSA levels lower than 2 ng/ml.) This occurred a median of 15 months after biochemical failure (PSA ≥ 0.2 ng/ml). And biochemical failure occurred a median of 24 months after prostatectomy. We know that waiting this long is sub-optimal.
A similar study at Memorial Sloan-Kettering Cancer Center looked at the site of failure after first-line radiation therapy to the prostate only (including seminal vesicles in some). They used CT scans (mostly) to detect sites of failure among 60 patients who had their first failure in the pelvic area. Spratt et al. found that, among those patients, only 42 percent would have the first detected lymph node metastasis treated by the standard pelvic lymph node radiation field. They found that expanding the field to include the common iliac lymph nodes would result in treatment of 93 percent of recurrences.
A study at University Hospital Munich used [18F]- or [11C]choline PET/CT scans to determine the site of lymph node involvement in 32 high-risk patients, and in 87 patients who were biochemically recurrent after prostatectomy. Locations of lymph node involvement were similar for both groups, with 39 percent of pelvic lymph nodes missed by the standard treatment field.
The other common method of treating pelvic lymph nodes is via extended pelvic lymph node dissection (ePLND). In one recent study, almost a quarter of positive lymph nodes would have been missed even if ePLND had been used.
It is possible that as advanced PET scans gain wider use, detection of smaller pelvic lymph node metastases will be possible. Jelle Barentsz at Radboud University Hospital in Nijmegen, Holland claims he can detect lymph nodes metastases as small as 2 mm using USPIO MRI. Even so, we are far from being able to detect all micrometastases in the pelvic area. If the goal is curative therapy, it is necessary to treat what we can’t see as well as what we can see.
Unfortunately, it is not always as simple as expanding the radiation treatment field or increasing the number of pelvic lymph nodes dissected surgically. As the treated area is widened, the risk for side effects increases. Lymphoceles and lymphedema are potentially crippling side effects of surgical excision. Damage to the enteric tissue of the small bowel and vascular damage become risk factors with wider radiation treatment fields. For anatomical reasons, not everyone is a good candidate.
Such risks have to be balanced against the evidence for the potential benefit of such treatment. The success of pelvic radiation in various settings was previously discussed here, and early results from the STAMPEDE clinical trial among N1 patients are encouraging.
Editorial note: This commentary was written by Allen Edel for the “New” Prostate Cancer InfoLink.