Positive Surgical Margins and Prostate Cancer–Specific Mortality

Selected by Pietro Cazzola

prostate cancerAn article published by Stephenson and colleagues in European Urology1 was intriguing because it provided new insight into an age-old question: Do positive radical prostatectomy surgical margins (PSM) alone lead to a higher rate of prostate–cancer specific mortality (CSM)?
Previous studies have addressed this question with variable results,2,3 but this study is unique in that it used the usual fixed covariates, such as age, Gleason sum, seminal vesicle invasion, lymph node involvement, PSA, and extra prostatic extension; however, these researchers also adjusted for postoperative radiotherapy, given early (pre-radiotherapy PSA ≤ .05 ng/mL) vs late (pre-radiotherapy PSA > 0.5 ng/mL).
The authors noted that 96% of the patients who received postoperative radiation therapy had a detectable pre-radiotherapy PSA level, and the late group had an increase in CSM, while the early group did not. They suggested that this may be due to the protective effect of early salvage radiotherapy in the early group, but that the late group likely had coexisting systemic disease. They further stated that this would argue against a policy of using adjuvant radiotherapy for all men with PSMs, given that as many as 60% will not require it. In addition, when early salvage radiation therapy is given, CSM rates are not affected by PSM alone. Further, they stated that it calls into question the relevance of PSM as a surrogate for surgical efficiency.
I would agree with the authors’ first statement, and generally feel that PSA alone is not an accurate prognostic indicator of CSM, but rather biochemical recurrence (BCR). Given that many of these patients will not experience a BCR, I have used a sensitive PSA assay (< 0.01 ng/mL) and watched for an early recurrence. In cases with PSM where the PSA is slowly increasing, but still < 0.2 ng/mL, I will discuss salvage radiation therapy and often deliver it early. However, I wait until the patients have had return of their continence and after a full disclosure of possible side effects, such as recalcitrant bladder neck contractures and potential worsening of continence and their erectile function. I agree that doing all that we can to avoid PSM and subsequent adjuvant therapies is a urologic oncology axiom that we apply to all cancer treatment.
My opinion differs slightly with that of the authors on their second point. Although we may be able to provide local control in the face of PSM with early salvage radiation therapy, this fact does not decrease the importance of avoiding PSMs, in my opinion, and to some extent does speak to the quality of the surgical approach, especially in cases of pT₂ tumors. In surgical practices where high PSM rates are noted with pT₂ tumors, surgical proficiency should be questioned; and I suspect in an era of increasing pressure to provide quality indicators, PSM rate will be under increasing scrutiny. Further, as the authors noted, we should all avoid PSMs, as they are a source of considerable anxiety in our patients, and, in their minds, reflects an inability to eradicate the cancer. As one of my previous mentors often stated, post-treatment PSA is an acronym for “patient-stimulated anxiety,” and, in cases of PSM, at least in the patient’s mind, we have increased their PSA.

References

  1. Stephenson AJ, Eggener SE, Hernandez AV, et al. Do Margins Matter? The Influence of Positive Surgical Margins on Prostate Cancer-Specific Mortality Eur Urol. 2014;65(4):675-680.
  2. Mauermann J, Fradet V, Lacombe L, et al. The impact of solitary and multiple positive surgical margins on hard clinical end points in 1712 adjuvant treatment-naïve pT₂-4 N0 radical prostatectomy patients. Eur Urol. 2013:64(1):19-25.
  3. Wright JL, Dalkin BL, True LD, et al. Positive surgical margins at radical prostatectomy predict prostate cancer specific mortality. J Urol. 2010;183(6):2213-2218.

 J. Brantley Thrasher