Which patients with a PSM post-surgery need early adjuvant therapy?

Could more intensive monitoring of PSA levels in the first few months after a radical prostatectomy help to determine which patients who have a positive surgical margin (PSM) need adjuvant radiation therapy and which don’t? A new paper by a team of clinical researchers in Prague has attempted to address this question in a paper in BMC Urology. The paper is also discussed on the Renal & Urology News web site.

Vesely et al. conducted a retrospective analysis of data from a series of 116 men, all of whom had a PSM post-surgery, and who had all been treated between 2001 and 2012. None of these patients had received any form of early adjuvant therapy (radiation therapy or androgen deprivation therapy). Furthermore, all these men had been intensively monitored post-surgery, with ultrasensitive PSA testing at days 14, 30, 60, 90 and 180, and then every 3 months.

The authors — and our regular readers too — were well aware that the finding of a PSM or PSMs in the pathology report post-surgery can affect risk for prostate cancer-specific outcomes. Adjuvant radiotherapy is known to be appropriate in some but not all of these patients. What we don’t know is how to differentiate between men with surgical margins and a rising PSA who are likely to benefit from adjuvant radiation therapy and those for whom there is likely to be little or no benefit.

Here are the core findings from the paper by Vesely et al.:

  • The average (median) patient follow-up was 31.4 months (rand, 6 to 69 months).
  • 55/116 patients (47 percent) exhibited biochemical recurrence (defined by a PSA level ≥ 0.2 ng/ml) during follow-up.
  • Risk for biochemical recurrence was not associated with the patients’ preoperative PSA level, pathologic Gleason sum, or pathologic grade.
  • Risk for biochemical recurrence was associated with the patients’ postoperative PSA levels at day 30 post-surgery.
  • Over the first 180 days post-surgery
    • A PSA level > 0.073 ng/ml at day 30 significantly increased risk for biochemical recurrence (hazard ratio [HR] = 4.35, p < 0.001).
    • Predictive accuracy of PSA testing was also significantly exceeded on day 60 (p < 0.001).
    • There was no increase in the predictive accuracy of PSA testing on days 90 and 180.
  • 16 patients had a PSA level of ≤ 0.01 ng/ml at day 30; and of those 16 patients, only 1 had a biochemical recurrence during follow-up.
  • Among 21/116 patients (28 percent) at risk for under-treatment in this series (because their PSA levels r4emained low at days 30 and 60 post-surgery), 18 demonstrated PSA progression at day 90, and only  2 patients had late biochemical recurrence (after 39 and 48 months).
  • Applying a PSA cut-off at day 30 as an indicator for adjuvant radiotherapy in this series would have lowered the risk of over-treatment from 61 to 8 patients.

The authors conclude that:

The level of ultrasensitive PSA yields valuable information about the prostatectomy outcome … at the first month after the surgery and should aid risk stratification in patients with PSM. Patients not likely to experience subsequent disease progression may be spared the toxicity of immediate adjuvant radiotherapy.

Here in the USA it has historically been standard practice not to give much credence to PSA data until 8 to 12 weeks (60 to 90 days) post-surgery as a method of determining outcomes after radical prostatectomy. These data from Vesely and his colleagues at least suggest the possibility that an initial, ultrasensitive PSA test at 30 days post-surgery might be helpful in determining which patients are at highest risk for post-surgical progression — if the patient has positive surgical margins. However, all patients would still need to be followed with further tests at 60 and 90 days post-surgery, with additional follow-up tests every 3 months for a period of time to be determined.

Clearly, it would be helpful to see data like this confirmed from a larger and more current surgical series of patients (if anyone else has consistently been collecting PSA levels at 30 days post-surgery). Monitoring patients on the basis of the data provided by Vesely et al. and making decisions about the need for adjuvant radiation therapy solely on their PSA data can not be justified on a relatively small, retrospective study like this.

4 Responses

  1. What is a PSM?

  2. I am 9 months out from my RP and had one PSM, I decided on surveillance and to wait on the adjuvant therapy. I just had a PSA done and I am still at < 0.01 after three PSA tests now. I have another one scheduled in 90 days and if I am still at < 0.01 we will discuss spacing out the tests even further.

  3. Grover:

    A PSM is a positive surgical margin, found after examination of the pathological specimen removed at surgery.

  4. As a patient on intermittent triple androgen deprivation therapy for the past 14 years until this past April, I have become familiar with research using ultrasensitive tests. These tests have been key to managing my case at the points my PSA fell to less than 0.1 ng/ml. (I have hit < 0.01 on two rounds of ADT3 and 0.02 on the third and fourth rounds, the latter following a curative attempt with radiation last year.)

    My impression is there is an effective consensus in research studies that recurrence is very likely after a radical prostatectomy if the PSA is increasing and the patient hits the 0.05 level, and fairly likely at the 0.04 level. Conversely, levels of 0.02, 0.01, and < 0.01 are increasingly favorable, with very low odds of a recurrence.

    That said, these past studies likely were dealing with follow-up tests beyond and well beyond 30 days. These findings at 30 days are really impressive and should be most useful in avoiding adjuvant radiation therapy in the PSM population if confirmed.

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