THE "NEW" PROSTATE CANCER INFOLINK

Is it still worthwhile to attempt salvage radiation therapy (SRT) after positive pelvic lymph nodes (PLN) have been pathologically detected (stage pN1)?

Traditionally, patients with PLN-diagnosed pN1 prostate cancer have been considered to have incurable systemic disease. Therefore, they were either observed until distant metastases were identified or started on lifelong androgen deprivation. Retrospective studies of the benefit of salvage whole pelvic SRT for pN1 patients have been equivocal: Abdollah et al. and Rusthoven et al. showed a benefit to SRT, but Kaplan et al. showed no benefit.

In an analysis of the National Cancer Database of 7,791 prostatectomy patients (treated from 2003 to 2010) who were staged pN1 after PLN detection, Zareba et al. found that

• Most (63 percent) were initially observed without treatment.
• An additional 20 percent received androgen deprivation (ADT) only within a year of diagnosis.
• Only 18 percent received SRT, most of those (72 percent of the 18 percent) with adjuvant ADT.

Those treated with whole pelvic SRT + ADT had worse post-prostatomy disease characteristics than those who were observed only: higher Gleason scores, higher stages, higher positive surgical margin rates, and greater numbers of positive lymph nodes.

After 5.9 years median follow-up on 3,680 patients:

• Treatment with whole pelvic SRT + ADT decreased 10-year mortality by 31 percent compared to observation only, and by 35 percent compared to ADT only.
• Treatment with ADT only or SRT only was not associated with an increase in survival.

Touijer et al. reported on 1,388 pN1 patients treated at three top institutions: Memorial Sloan-Kettering Cancer Center (MSKCC), the Mayo Clinic, and San Raffaele Hospital in Milan. The MSKCC cohort was primarily only observed; the Mayo cohort primarily received lifelong ADT only; and the Milan cohort was primarily treated with whole pelvic SRT + ADT. As in the Zareba study, SRT + ADT patients had worse disease characteristics.

After 5.8 years median follow-up:

• Treatment with whole pelvic SRT + ADT decreased 10-year mortality by 59 percent compared to observation only, and by 54 percent compared to ADT only.
• Those with worse disease characteristics benefited the most.
• Treatment with ADT only was not associated with an increase in survival compared to observation, although prostate cancer-specific survival was increased.

None of these studies reported the toxicity of the salvage treatment, but with improved external beam radiation techniques and scrupulous image guidance, toxicity has been improving.

These two studies had very similar outcomes. Although they were both retrospective studies rather than prospective randomized trials, it should be noted that the selection bias that typically plagues retrospective studies favored those who did not receive SRT + ADT. In spite of their worse disease characteristics, the patients who received SRT + ADT survived longer.

Recently we saw a similar advantage to pelvic SRT + ADT even in men who were not diagnosed as stage pN1 with a positive PLN (see this link). Taken together, these studies indicate a marked survival advantage to treating the whole pelvic area in men with pathologically diagnosed, high-risk prostate cancer post-prostatectomy. A previous study found that among men with pN1, the 10-year incidence of distant metastases was 35 percent, suggesting that spread may be confined to pelvic lymph nodes for some time. This creates a unique window of opportunity during which salvage treatment may still be curative.

We have also seen evidence that high-risk patients with imaging-detected positive lymph nodes benefited from whole pelvic radiation as primary therapy

These studies constitute better evidence than we currently have that whole pelvic radiation with ADT is a better idea than picking off lymph nodes one at a time (for which we have no evidence of survival benefit). As we have seen, our ability to detect all cancer-affected lymph nodes is poor.

There are several variables that the patient and doctor must decide upon, and for which there is no clear evidence: duration of adjuvant ADT, amount of radiation, and the pelvic lymph node field. Clinical trials show that at least 6 months of adjuvant ADT with SRT — even without lymph node involvement — increases oncological effectiveness; the optimal duration is unknown and may vary with disease characteristics. The amount of radiation to the pelvic lymph node field seems to be about 50 Gy in most cases, and the amount given simultaneously to the prostate bed will ideally be at least 70 Gy. The extent of the treated area has been questioned recently. Studies show that affected lymph nodes are often missed in the common iliac area. There will be variations due to individual anatomy and known bowel sensitivity.

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: ADT, lymph, node, pN1, positive, radiation, salvage, stage, therapy |