Original ReportMargin involvement at prostatectomy for clinically localized prostate cancer: Does a low-risk group exist?
Introduction
An involved surgical margin at prostatectomy has long been established as a risk factor for prostate cancer recurrence.[1], [2] While phase 3 randomized trials have demonstrated improved disease control,[3], [4], [5] disease-specific survival,6 and distant metastasis-free survival6 benefits for immediate postoperative (adjuvant) radiation therapy in the setting of high-risk features (including involved margin), even these studies demonstrated an estimated 30%-40% of patients who did not have prostate-specific antigen (PSA) relapse at 10 years postprostatectomy.[6], [7] Thus, some patients may not require adjuvant therapy and may be safely observed; however, at present, identification of this “low-risk” subset remains to be determined. The present investigation seeks to determine whether additional pathology details concerning the involved margin(s) may permit substratification of patients without other high-risk features (seminal vesicle or lymph node involvement) into low- and high-risk groups for specifying postoperative management.
Section snippets
Methods and materials
Following institutional review board approval at the study institution, a research database was created with study-specific patient, treatment, and outcome data fields. Eligible cases were identified by review of medical records and quality assurance database. After selection for prostate adenocarcinoma cases, a review of patient records was performed in order to eliminate patients with advanced or metastatic disease at diagnosis (including preprostatectomy evidence of seminal vesicle or pelvic
Results
Between January 2003 and December 2010, 355 patients diagnosed with adenocarcinoma of the prostate underwent radical prostatectomy at the study institution. Of these, 279 were eligible for inclusion in the present study. Reasons for exclusion were involved seminal vesicles or nodes (n = 37), postprostatectomy follow-up < 12 months (18), prostatectomy outside study period (5), hormone therapy prior to prostatectomy (6), missing records (3), PSA ≥ 20 (6), and adjuvant radiation therapy (1). Patient
Discussion
Involvement of a surgical margin at prostatectomy has long been associated with increased risk of PSA failure.[1], [2] Despite presence of tumor cells at the margin, however, not all patients will experience PSA failure within 5-10 years postprostatectomy. Presently, consensus guidelines recommend consideration of adjuvant radiation therapy in the setting of high-risk pathologic features, including involved margin,9 based upon large, mature randomized trials demonstrating 50% reduction in risk
Conclusions
Within the present study, Gleason score 6 patients with margin width ≤ 4 mm appear to have low rates of early PSA relapse following radical prostatectomy. Low-grade cases with wider margin(s) or higher risk Gleason score patients with any margin involvement have high rates of early PSA relapse.
References (24)
- et al.
Use of Gleason score, prostate specific antigen, seminal vesicle, and margin status to predict biochemical failure after radical prostatectomy
J Urol
(2001) - et al.
Do margins matter? The prognostic significant of positive surgical margins in radical prostatectomy specimens
J Urol
(2005) - et al.
Postoperative radiotherapy after radical prostatectomy: A randomised controlled trial (EORTC trial 22911)
Lancet
(2005) - et al.
Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: Long-term followup of a randomized clinical trial
J Urol
(2009) - et al.
Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: Long-term results of a randomised controlled trial (EORTC trial 22911)
Lancet
(2012) - et al.
Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline
J Urol
(2013) - et al.
Salvage radiotherapy for rising prostate-specific antigen levels after radical prostatectomy for prostate cancer: Dose-response analysis
Int J Radiat Oncol Biol Phys
(2010) - et al.
IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients treated with post-operative adjuvant or salvage radiotherapy after radical prostatectomy
Radiother Oncol
(2009) - et al.
Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer
Int J Radiat Oncol Biol Phys
(2008) - et al.
High-dose adjuvant radiotherapy after radical prostatectomy with or without androgen deprivation therapy
Int J Radiat Oncol Biol Phys
(2012)
Comparison of adjuvant versus salvage radiotherapy policies for postprostatectomy radiotherapy
Int J Radiat Oncol Biol Phys
Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy
Int J Radiat Oncol Biol Phys
Cited by (7)
A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy
2021, Advances in Radiation OncologyCitation Excerpt :To our knowledge, this is the only study to implement RPA stratification to identify potential low- and high-risk cohorts with more than 200 margin-positive patients and median follow-up over 8 years. The bRFS at 8 years of those with GG1 disease with cumulative margin 2 mm or less was historically comparable (92%) to those with negative margins.6,19 Additionally, approximately 50% of patients with GG2 and positive margins experienced biochemical failure at 8 years.
Gleason Score ≤ 6 Prostate Cancer at Radical Prostatectomy: Does a High-Risk Setting Truly Exist? A Recursive Partitioning Analysis
2017, Clinical Genitourinary CancerCitation Excerpt :Further, the benefit of adjuvant RT appears to be maintained in the setting of the bladder base as the sole site of margin involvement.19 The extent of involvement at the margin site(s) has also been evaluated, and linear extent of the margin has consistently shown an inverse association with bRFS,14,20-22 even within G6PC specifically.20 The association between longer interval between biopsy to RP and PSA relapse in multivariable analysis was interesting.
Individualization of Adjuvant Therapy after Radical Prostatectomy for Clinically Localized Prostate Cancer: Current Status and Future Directions
2016, Clinical Genitourinary CancerCitation Excerpt :Another method by which to evaluate involved surgical margins is to measure the linear extent of disease at the surgical margin. One investigation of 114 adjuvant therapy-naive patients with involved surgical margins identified the linear extent of the positive margin to be significantly associated with early PSA recurrence.17 Additionally, when stratified by the Gleason score at prostatectomy, a subset of patients with a low risk of early recurrence was identified.
Margin details matter: The prognostic significance of pseudocapsule invasion at the site of involved margin in prostatectomy specimens
2015, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :This aligns well with 33% to 60% reported elsewhere in the literature [4,5,8,9]. Further, these findings build on previously-reported experiences of pathology-determined subset creation, including extent of margin involvement (particularly when analyzed by Gleason score of the prostatectomy specimen) [6,7]. In 1 retrospective series, investigators from the University of Western Ontario (Canada) described outcomes for patients with node-negative/seminal vesicle-uninvolved prostatectomy with EPE and involved margins [7].
Conflicts of interest: None.