Radiation therapy may improve survival even when PSA ≥ 75 ml/ml

Sometimes, when patients originally present with very high PSA levels, a negative bone scan, and a negative CT scan, they are put on permanent androgen deprivation  therapy (ADT) because the doctor just assumes it is micrometastatic. A closer look at the data demonstrates that an attempt at curative radiation may improve outcomes.

Lawrence et al. screened the 2004-2008 SEER database, and found 75,539 patients diagnosed with non-metastatic prostate cancer, and excluded those treated with surgery or brachytherapy. The patients had a median age of 70 years. Their findings based on a median of 60 months of follow up were:

  • Use of radiation therapy (RT) was associated with a reduction in prostate cancer mortality of 59 percent.
  • 4-year prostate cancer survival was 94 percent in those who had RT vs. 77 percent in matched patients who had no local therapy.
  • The benefit held even for those with PSA levels ≥ 75 ng/ml

Three important caveats:

  1. This is a retrospective study and is subject to selection bias. This means that those who received no local therapy may have done so for reasons not readily apparent in the available records. Although the authors made an attempt to account for age, grade, PSA level, stage, and perhaps other variables, there may have been signs of greater progression that the doctor was aware of.
  2. The PSA values recorded in the SEER database have recently been called into question. Interested readers may read more about this here. In fact, the National Cancer Institute has withdrawn PSA data from the current files. This analysis was evidently performed before that withdrawal on April 29, 2015. This does not affect the survival data.
  3. A median of 60 months of follow up is not long enough to determine whether survival benefits are sustained in the long run. Neither the radiation-treated cohort nor the non-treated cohort reached median survival during the time period of observation so far available.

Given those caveats, we can only conclude that there may be something to this, but that can only be determined by a clinical trial where patients with extremely high PSA levels (but negative bone and CT scans) are randomized to radiation therapy or ADT only (and perhaps a combination of the two), and they are tracked for 10 years or more. The study does suggest that PSA alone is not a good risk factor on which to base the decision about whether to pursue curative therapy.

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

2 Responses

  1. I have to take serious issue with the conclusion “… that can only be determined by a clinical trial where patients with extremely high PSA levels (but negative bone and CT scans) are randomized to radiation therapy or ADT only (and perhaps a combination of the two) …”

    This does not reflect medical practice in recent years to the extent that I doubt such a trial would get past an ethics committee in 2015.

    Take my own case: diagnosed in 2010 with a presenting PSA of 330 ng/ml but a negative bone scan and MRI scan resulting in a presumed T4N0M0 status. The results of PRO7 and the change in thinking about the treatment of locally advance prostate cancer was a hot topic at the time. Here is link to one of many articles from 2010 on this topic.

    There was no suggestion that I should not have radiotherapy. I also entered the STAMPEDE trial and was interested to note that STAMPEDE stopped accepting locally advanced patients who had not had radiotherapy — unless their oncologist could justify its omission. In other words radiotherapy for locally advanced prostate cancer had become the default option even as far back as 2010.

    And remember this: I am talking about treatment from the UK’s cash-strapped NHS!

    Cormac Murphy

  2. Perhaps you are mistaking my comments about a flawed research study for a recommendation about what clinicians and patients ought to do.

    The study reviewed here was based on an analysis of the US SEER database of patients treated, many with ADT only, during 2004-2008. I personally believe that most patients with high PSAs and no discernable distant metastases ought to have definitive therapy, but that does not always happen in actual practice. It does reflect recent medical practice and it is not considered unethical to treat very high-risk patients with ADT only. In their 2015 guidelines, NCCN lists “ADT in select patients” as an acceptable initial therapy option.”Select patients” are those who are not considered by the clinician to be good candidates for definitive therapy. I hope that clinicians are considering a wider range of patients as good candidates; however, as we showed in a recent article, older men, particularly, are under-treated with definitive radiation therapy. Unfortunately, some men, especially those treated in community practice, are never availed of all their options.

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