2021, Volume 37, Number 3, Page(s) 233-238
Does the Distance of the Tumor from the Surgical Margin Affect Biochemical Recurrence in Patients with Pathological Organ-Confined Prostate Cancer?
Ayse OZBEK1, Rýdvan OZBEK2, Mehmet DUVARCI3, Olcay KANDEMIR1
1Department of Pathology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ministry of Health - University of Health Sciences, ANKARA, TURKEY
2Department of Urology, Kecioren Training and Research Hospital, Ministry of Health - University of Health Sciences, ANKARA, TURKEY
3Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ministry of Health - University of Health Sciences, ANKARA, TURKEY
Keywords: Surgical Margins, PSA, Prostate Cancer, Biochemical recurrence
To investigate the effect of the distance between tumor and surgical margin on biochemical recurrence in patients with organ-confined
Material and Method: The data of 208 patients, who underwent radical prostatectomy between 2012-2018, were retrospectively analyzed.
The surgical margin status of 147 pathologically organ-confined patients was categorized as positive, close (<1mm) and negative. Surgical
margin status and parameters affecting biochemical recurrence were examined. Furthermore, multivariate analysis was done to determine the
parameters associated with biochemical recurrence.
Results: Biochemical recurrence was detected in 21 (14.2%) of 147 patients. 38 (27.9%) men had negative surgical margins, 68 (46.2%) had
close surgical margins and 41 (25.9%) had positive surgical margins. Tumor volume and ISUP grade were found to be statistically significant
for positive surgical margin and close surgical margin patients compared to negative surgical margin patients. Close surgical margin was not
statistically associated with biochemical recurrence. Preoperative high PSA (p<0.001) and positive surgical margin (p=0.021) were independent
risk factors for biochemical recurrence.
Conclusion: According to our results, it is not necessary to include the presence of a close surgical margin in the pathology reports in patients
with pathological organ-confined tumors and negative surgical margins.
Biochemical recurrence (BCR), which is one of the
important markers in predicting prognosis following
radical prostatectomy, is associated with various factors,
and surgical margin positivity is one of the leading
ones. Studies reveal that surgical margin positivity is an
independent predictive factor in terms of BCR and cancerspecific
On the other hand, BCR in cases with localized prostate
carcinoma, where the positive surgical margin is not
observed, suggests that not only the tumor’s contact with
the surgical margin but also its proximity may affect the
development of recurrence 4-7.
Although positive surgical margin rates decrease with
developing surgical techniques, radical prostatectomy
operations performed to maintain urinary and sexual
function generally cause the prostate to be removed with
surgical margins close to the tumor.
Even if the tumor is too close to an inked surface, the
surgical margin is considered negative if it does not come
into contact with the ink. However, the definition of surgical
margin proximity for prostate cancer is not yet clear. In
some cancers, the tumor’s proximity to the surgical margin
has been shown to be correlated with the risk of recurrence.
For example, in colon carcinoma, it has been stated that
tumors close to the radial surgical margin and tumors that
contact with the surgical margin have a similar rate of local
and distant recurrence 8,9. In prostate cancer, the cut-off
values taken for the definition of the tumor’s proximity
to the surgical margin vary and the effect of this factor on
biochemical recurrence remains unclear.
We aimed to investigate the effect of surgical margin
status on biochemical recurrence in pathologically organconfined
This study was approved by the ethics committee (approval
number 2019-04/254). The data of 208 patients, who
were treated with radical prostatectomy for prostate
adenocarcinoma between 2012 and 2018 in a single referral
center, were retrospectively analyzed. 10 patients with node
positive (pN+), 23 patients with seminal vesicle invasion
(pT3b), and 28 patients with extracapsular extension (pT3a)
were excluded from the study. None had preoperative
androgen deprivation therapy or radiotherapy. In total, 147
patients (pT2) were enrolled in the study.
Clinical and pathological data included age, prostate
specific antigen, prostate volume, tumor volume,
International Society of Urological Pathology (ISUP) grade
group, lymphovascular invasion, perineural invasion,
biochemical recurrence and surgical margin status. Followup
schedules were developed by the surgeon in accordance
with the European Association of Urology (EAU) prostate
cancer guidelines. Biochemical recurrence was defined as
Analysis of Surgical Specimens
Before macroscopic sampling, all specimens were left in
10% formalin for 18-24 hours. Afterward, the dimensions
of the specimens were recorded, and the specimen surfaces
were painted with ink. The entire material was sliced from
the apical (distal) to the basal (bladder neck) into 3 mm
thick sections and blocked for embedding in paraffin. Two
sections with 3-4 micron thickness were taken from the
blocks and examined under a microscope. All cases were
re-evaluated by one pathologist according to the 2014 ISUP modified Gleason grading system. While evaluating
surgical margins, contact of tumor cells with the dye in
the areas with surgical border staining was considered as
positive surgical margin (PSM) (Figure 1). A close surgical
margin (CSM) was reported when the tumor approached
the margin by less than 1 mm (Figure 2).
All statistical analyses were performed using the SPSS
22.0 (IBM SPSS Statistics, IBM Corporation, Chicago, IL)
software for Windows. The compliance of the numeric
variables with the normal distribution was assessed
with the Kolmogorov-Smirnov test. Demographic and
clinicopathologic features were compared between the
three surgical margin groups using Kruskal-Wallis tests
and One-Way Anova tests for continuous variables and
Chi squared tests for categorical variables. Significant
parameters in the Kruskal-Wallis test were compared
in binary groups using the Mann-Whitney U test. The
median (interquartile range, IQR) was used to define the
non normally distributed variables, while frequency and
percentage were used for categorical variables. In all the
analyses, the statistical significance level was accepted as
The study group included 147 patients with pathologically
organ-confined prostate cancer. Of these, 38 (27.9%) men
had negative surgical margins (NSM), 68 (46.2%) had
close surgical margins and 41 (25.9%) had positive surgical
margins. Demographic and clinicopathologic data are
presented in Table I
Click Here to Zoom
|Table I: Patients’ demographic and clinicopathologic characteristics by surgical margin status
PSA values were found to be significantly higher in the
patients with PSM compared to the patients with CSM
(p=0.005). Tumor volume was statistically significantly
higher in PSM and CSM groups compared to NSM (p=0.018
PSM vs NSM, p=0.007 CSM vs NSM). Furthermore, it was
observed that the patients in the PSM and CSM groups had
higher ISUP grade compared to the patients in the NSM
group (p=0.004). After a median follow-up of 12.3 months,
BCR occurred in 4 (19%), 5 (23.9%), and 12 (57.1%)
patients with negative, close and positive surgical margins,
respectively (Table II).
In univariate analysis, we discovered a statistically
significant relationship between preoperative PSA value
(p<0.001), tumor volume (p=0.001), ISUP grade group 4-5 (p=0.027), PSM (p=0.017), CSM (p=0.006) and BCR.
In multivariate analysis, a high preoperative PSA value
(p<0.001) and PSM (p=0.021) were found to be statistically
significant (Table III).
Click Here to Zoom
|Table III: Uni- and multivariate logistic regression analysis for predictors of Biochemical Recurrence.
European Association of Urology (EAU) current guidelines
state that surgical margin positivity, high preoperative PSA,
high ISUP grade and high pathological stage in the specimen
after radical prostatectomy are risk factors in terms of BCR
. In our study, the relationship between the distance of
the tumor to the surgical margin and BCR was investigated
in the group with pathological organ-confined prostate
cancer (pT2). As a result of the multivariate analysis, it was
determined that the distance of the tumor to the surgical margin did not affect the BCR, while the independent
factors affecting the BCR were surgical margin positivity
and preoperative PSA value.
Biochemical recurrence may develop during follow-up
in the patients who had organ-confined prostate cancer
and underwent radical prostatectomy. In a recent study
conducted by Stolzenbach et al., 5-year BCR-free survival
rates in pathological organ-confined prostate cancer
were reported to be approximately 88% 11. Aoun et al.
associated the BCR development in pT2 prostate cancer
with factors such as insufficient diagnosis of surgical
margin positivity, limited sections examined even though
the entire specimen was sampled, PSA secretion of the
postoperative residual benign prostate tissues and occult
lymph node metastasis 12.
The presence of tumor closer than 1 mm to the painted
surgical margin was accepted as CSM when defining the
proximity to the surgical margin in this study. While
determining this, we considered the existence of the
publications accepting a value of 1 mm in the literature
13,14. Whalen et al. have found that BCR developed
more commonly in patients with close surgical margins
than patients with negative surgical margins. They even
stated that the patients with CSM showed similar rates of
BCR development as the patients with PSM 13. Similarly,
Herforth et al. have shown that proximity to the surgical
margin increased BCR. However, they emphasized that
in the absence of high-risk parameters for BCR, surgical
margin status alone did not increase metastasis, prostate
cancer specific mortality and all-cause mortality, and that
surgical margin status alone should not be used to decide
adjuvant treatment 14. In our study, contrary to these studies, we found that the presence of tumor close to the
surgical margin did not affect BCR in organ-confined
In some studies, the presence of a tumor closer than 0.1
mm to the surgical margin was accepted as ‘close surgical
margin’. Lu et al. have found that the Gleason score and
the presence of positive surgical margin were the strongest
prognostic factors affecting BCR, and the presence of
tumors close to the surgical margin led to the development
of BCR 15. In another study, Izard et al. have shown that
the presence of tumors close to the surgical margin had
a similar rate of BCR risk as in the patients with positive
surgical margins. In these studies, the distance of 0.1
mm was measured by comparing it to either the visual
field diameter or fibroblast size 16. We think that the
evaluation of this proximity according to the visual field
diameter or the width of a few fibroblasts is subjective and
will vary between pathologists. Moreover, prostatectomy
materials are macroscopically sampled in approximately 3
mm thick pieces and then 3-4 micron sections are obtained
and examined. The fact that the tumor is closer than 0.1
mm in these sections suggests that the surgical margin may
be positive in the following sections as stated by Izard et al.
in their study, and this situation remains uncertain since
all tissues cannot be examined microscopically. For these
reasons, we considered the presence of a tumor closer than
1 mm to the surgical margin as ‘close surgical margin’ in
EAU prostate cancer guidelines have emphasized that
extraprostatic spread, seminal vesicle invasion and lymph
node invasion may increase the risk of BCR 10. In the
literature, there are patients with these parameters in the study cohorts that indicate a relationship between the
distance to the surgical margin and BCR. We believe that
evaluating these parameters and proximity to the surgical
margin together affects the research results. Therefore, we
have excluded the patients with extraprostatic invasion,
seminal vesicle invasion and lymph node positivity on
pathology in the study group.
This study has some limitations to consider, including the
retrospective design and shorter follow-up time compared
to other studies. In addition, the relatively small number of
the patients is seen as another limiting factor. The reason
for this is that patients with organ-confined prostate
cancer (pT2) were included in the study. Although this
limits the number of patients, it makes our study more
valuable. Moreover, the evaluation of all sections by the
same pathologist eliminated an interobserver evaluation
In our study, we showed that preoperative PSA value and
PSM are independent factors that increase the risk of BCR
in the multivariate analysis in patients with organ-confined
prostate cancer. We also found that tumor closer than 1
mm to the surgical margin had no effect on the risk of BCR.
In the light of these results, we believe that the presence
of a close surgical margin should not be included in the
pathology reports of patients with pathological organconfined
and negative surgical margin.
CONFLICT of INTEREST
The authors of this manuscript declare no conflict of
The authors state that this work has not received any
Concept: AO, OK, Design: AO,RO, Data collection or
processing: AO, RO, MD, Analysis or Interpretation: AO,
RO, Literature search: AO, Writing: AO, OK, Approval:
AO, RO, MD, OK.
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