Pelvic lymph node treatment area is seldom wide enough

A Mayo Clinic study sought to determine exactly where the recurrences were after failure of prostatectomy. Parker et al.  studied recurrence in 41 patients who received a post-prostatectomy C-11 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 salvage radiation, using at least 45 Gy of external beam radiation. They classified their recurrence sites as:

1. IF (in-field) if the recurrence site would receive at least 45 Gy
2. EOF (edge of field) if the recurrence site would receive less than 45 Gy (inadequate dose)
3. OOF (out of field) if the recurrence site would not receive any radiation

They identified 121 recurrence sites. A sizeable minority (43%) 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% had IF recurrences
• 24% had EOF recurrences (median dose - 10 Gy)
• 88% had OOF recurrences.
• 15% had both EOF and OOF recurrences.
• 10% had both IF and OOF recurrences.

It should be mentioned that the patients did not receive the PET scans until their PSA reached a median of 3.1 ng/ml (C-11 Choline PET isn't much good at PSAs 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 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% would have the first detected lymph node metastasis treated by the standard pelvic lymph node radiation field. They found that by expanding the field to include the common iliac lymph nodes would treat 93% of recurrences.

A study at University Hospital Munich used F-18 or C-11 Choline PET scans to determine the site of lymph node involvement in 32 high-risk patients, and in 87 patients who were biochemically recurrent after prostatectomy. Location of lymph node involvement was similar for both groups, with 39% of pelvic LNs missed by the standard treatment field.

A similar study at the University of Kansas, using C-11 Acetate PET scans found that over half of all positive pelvic lymph nodes would have been missed by the standard radiation field. Notably, 78% of all positive lymph nodes were smaller than 1 cm, and therefore would have been missed if only a CT scan were used to identify them.

A similar study found that 39% of pelvic LNs would have been missed.

(Update 5/2019) De Bari et al. used a PSMA PET scan to identify sites of recurrence after prostatectomy failure. They found:

• 75% of patients had a nodal relapse outside of the traditional (RTOG) field
• To cover 95% of the nodal relapses, the radiation field size would have to be expanded to include the para-aortic lymph nodes up to T12-L1

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 LNs 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 LN metastases will be possible. Jelle Barentsz at Radboud University Hospital in Nijmegen, Holland claims he can detect LN 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 LNs dissected surgically. As the treated area is widened, the risk of side effects increase. 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.

(Update 9/1/20) NRG Oncology expanded its recommendation for the treatment of pelvic lymph nodes (see this link).

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 discussed here, and early results from the STAMPEDE clinical trial among N1 patients are encouraging.