The impact of solitary and multiple positive surgical margins on hard clinical end points in 1712 adjuvant treatment-naive pT2-4 N0 radical prostatectomy patients.
BACKGROUND
Positive surgical margins (PSMs) increase the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), but their impact on hard clinical end points is a topic of ongoing discussion.


OBJECTIVE
To evaluate the influence of solitary PSMs (sPSMs) and multiple PSMs (mPSMs) on important clinical end points.


METHODS
Data from 1712 patients from the Centre Hospitalier Universitaire de Québec with pT2-4 N0 prostate cancer (PCa) and undetectable prostate-specific antigen after RP were analyzed.


METHODS
RP without neoadjuvant or adjuvant treatment.


METHODS
Kaplan-Meier analysis estimated survival functions, and Cox proportional hazards models addressed predictors of clinical end points.


CONCLUSIONS
Median follow-up was 74.9 mo. A total of 1121 patients (65.5%) were margin-negative, 281 patients (16.4%) had sPSMs, and 310 patients (18.1%) had mPSMs. A total of 280 patients (16.4%) experienced BCR, and 197 patients (11.5%) were treated with salvage radiotherapy (SRT). Sixty-eight patients (4.0%) received definitive androgen deprivation therapy, 19 patients (1.1%) developed metastatic disease, and 15 patients (0.9%) had castration-resistant PCa (CRPC). Thirteen patients (0.8%) died from PCa, and 194 patients (11.3%) died from other causes. Ten-year Kaplan-Meier estimates for BCR-free survival were 82% for margin-negative patients, 72% for patients with sPSMs, and 59% for patients with mPSMs (p<0.0001). Time to metastatic disease, CRPC, PCa-specific mortality (PCSM), or all-cause mortality did not differ significantly among the three groups (p=0.991, p=0.988, p=0.889, and p=0.218, respectively). On multivariable analysis, sPSMs and mPSMs were associated with BCR (hazard ratio [HR]: 1.711; p=0.001 and HR: 2.075; p<0.0001), but sPSMs and mPSMs could not predict metastatic disease (p=0.705 and p=0.242), CRPC (p=0.705 and p=0.224), PCSM (p=0.972 and p=0.260), or all-cause death (p=0.102 and p=0.067). The major limitation was the retrospective design.


CONCLUSIONS
In a cohort of patients who received early SRT in 70% of cases upon BCR, sPSMs and mPSMs predicted BCR but not long-term clinical end points. Adjuvant radiotherapy for margin-positive patients might not be justified, as only a minority of patients progressed to end points other than BCR. PCSM was exceeded 15-fold by competing risk mortality.
Department of Surgery, Laval University, Quebec City, QC, Canada.
Julian
J
Mauermann
Vincent
V
Fradet
Louis
L
Lacombe
Thierry
T
Dujardin
Rabi
R
Tiguert
Bernard
B
Tetu
Yves
Y
Fradet
D000726:Androgen Antagonists / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000097:blood; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D016009:Chi-Square Distribution; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000097:blood; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D016016:Proportional Hazards Models; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000601:surgery; D011792:Quebec; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human