Prognostic significance of a positive surgical margin in pathologically organ‐confined prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To identify risk factors of a positive surgical margin (PSM) and the significance of a PSM after radical prostatectomy (RP) on biochemical recurrence (BCR) in exclusively pathologically confirmed organ‐confined (OC) prostate cancer, as despite an excellent prognosis after RP, some patients with pathologically confirmed OC disease have BCR, and the prognostic significance of a PSM in these men remains unclear.

PATIENTS AND METHODS

We assessed 932 men with pathologically OC disease who were treated with RP by nine different surgeons between 1992 and 2004. The prognostic significance of clinical and pathological variables, including tumour volume (TV) and percentage of high‐grade TV (%HGTV) were assessed. Logistic and Cox regression models were fitted to identify risk factors of a PSM and BCR. BCR was defined as a prostate‐specific antigen (PSA) level of 0.1 ng/mL and increasing after an undetectable PSA level.

RESULTS

The total PSM rate was 12.9% (120 men); the mean TV (P < 0.001), but not %HGTV (P= 0.2) was significantly higher in patients with PSM. TV, nerve‐sparing RP technique and surgical volume were independent risk factors for a PSM (P= 0.03). After a median follow‐up of 35 months the overall BCR rate was 8.8% (82 men). Patients with a PSM had significantly higher BCR rates (21.7% vs 6.9%; P < 0.001). In univariable analysis, a high %HGTV (70.4%) was the most informative risk factor of BCR, followed by RP Gleason score (65.8%) and PSM (65.7%). Removal of PSM from a multivariable Cox model decreased the accuracy by 12.1% (P < 0.001).

CONCLUSIONS

Our findings show that in OC prostate cancer, the risk of a PSM depends on TV, surgical technique and surgical volume. PSM is a significant risk factor for BCR. However, only 20% men with OC disease and a PSM develop BCR; conversely, 80% of men are cured despite a PSM. Therefore, adjuvant therapy must be considered, with caution to avoid unnecessary overtreatment.     

Differences in histopathological and biochemical outcomes in patients with low Gleason score prostate cancer

Study Type – Diagnosis (case series)
Level of Evidence 4

OBJECTIVE

To test whether the number or percentage of positive biopsy cores can be used to discriminate between patients with prostate cancer of a favourable and less favourable Gleason score (GS) ≤3 + 3, as prognostically, not all GS 3 + 3 prostate cancers are the same.

PATIENTS AND METHODS

In all, 1106 consecutive patients with a prostate‐specific antigen (PSA) level of ≤10 ng/mL and a biopsy GS of ≤3 + 3 or 3 + 4 had an open radical prostatectomy. The number of positive biopsy cores (≤2 vs ≥3) were stratified into low‐ vs high‐risk groups. Subsequently, we stratified patients according to the GS and the percentage of positive biopsy cores (<50% vs ≥50%). The pathological stage and the 5‐year biochemical recurrence (BCR)‐free survival rates were examined in univariable and multivariable models.

RESULTS

Based on the number of positive cores, the rate of extraprostatic disease was 11.7% and 23.3%, respectively, in the low‐and high‐risk GS ≤3 + 3 groups (P < 0.001). The 5‐year BCR‐free survival rates were 95.0%, 77.8%, 81.2% and 66.5% for, respectively, low‐ and high‐risk GS ≤3 + 3 and for low‐ and high‐risk GS 3 + 4 patients. Univariable and multivariable intergroup BCR rate differences were statistically significant between low‐ vs high‐risk GS 3 + 3 patients (P < 0.001), but not significant between high‐risk GS ≤3 + 3 vs low‐risk GS 3 + 4 patients (P = 0.6). Comparable results were obtained when comparisons were made according to the percentage of positive biopsy cores.

CONCLUSIONS

Our results corroborate the finding that not all patients with a biopsy GS of ≤3 + 3 prostate cancer have low‐risk disease. High‐risk GS ≤3 + 3 patients have a similar risk profile as more favourable GS 3 + 4 patients. This finding warrants consideration when deciding on treatment.     

Location and number of positive surgical margins as prognostic factors of biochemical recurrence after salvage radiation therapy after radical prostatectomy

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To determine if the location and number of positive surgical margins (PSMs) after radical prostatectomy (RP) are associated with recurrence after salvage external beam radiation therapy (sEBRT).

PATIENTS AND METHODS

We retrospectively reviewed the medical records of 60 patients with PSMs who underwent three‐dimensional conformal sEBRT for biochemical recurrence (BCR) or clinically detected local recurrence after RP between 1996 and 2007. PSMs were categorized as present or absent at three locations, and patients were classified as having either one or more than one PSM. BCR after RP was defined as a prostate‐specific antigen (PSA) level of ≥0.1 ng/mL. BCR after sEBRT was defined as a serum PSA level of ≥0.1 ng/mL above the PSA nadir after sEBRT.

RESULTS

In all, 24 (40%) patients had more than one PSM. Overall, the most common location of a PSM was the posterior prostate with 40 (66%) patients having a positive posterior margin. The location of PSMs was not significantly associated with secondary BCR (global P= 0.8). There was a borderline result between the number of PSMs and BCR: men with more than one PSM were less likely to recur compared with those with only one PSM (hazard ratio 0.42; P= 0.067).

CONCLUSIONS

This is the first study to specifically analyse location and number of PSMs as prognostic factors for men who undergo sEBRT. There was no evidence to suggest that the location of a PSM predicted secondary BCR. Further research is needed to determine whether the number of PSMs is an important predictor of BCR after sEBRT.     

Length of site‐specific positive surgical margins as a risk factor for biochemical recurrence following radical prostatectomy

Objectives: Positive surgical margins (PSM) have been associated with biochemical recurrence (BCR) after radical prostatectomy, but the significance of PSM length and location are debated. We assessed the impact of PSM lengths at specific locations for BCR in an open radical prostatectomy series. Methods: Detailed clinical and pathological data were collected from 117 post‐prostatectomy patients with PSM from 1984 to 2004 at our institution. PSM locations were classified as apex, mid‐gland, base, bladder neck, and anterior fibromuscular region with lengths measured at each site. Aggregate PSM length was obtained by summing lengths of all PSM areas in contact with the inked surface. BCR was defined as serum prostate specific antigen level 0.2 ng/mL or greater. Cox proportional hazards regression analyses of PSM lengths were conducted either as a continuous or categorical variable relative to location as a predictor of BCR. Results: Multivariate analyses demonstrated that as a continuous variable, PSM length at the anterior fibromuscular region (Hazard ratio [HR] = 1.17; P = 0.027) and bladder neck (HR = 1.29; P = 0.046) were significant predictors for BCR. As a categorical variable, PSM length ≥ 2 mm at the anterior fibromuscular area was significant for BCR (HR = 3.02; P = 0.036). Increasing Gleason grade and positive lymph node status were also found to be significant independent predictors for BCR. Conclusion: PSM length at the anterior fibromuscular region (continuous and categorical) and the bladder neck (continuous) was significantly associated with BCR. Site‐specific PSM length, along with Gleason grade and lymph node status, can be predictive of BCR and assist in risk stratification of patients with PSM following radical prostatectomy.     

Prostate‐specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer

Objective

To clarify the impact of prostate‐specific antigen screening on surgical outcomes of prostate cancer.

Methods

Patients who underwent radical prostatectomy were divided into two groups according to prostate‐specific antigen testing opportunity (group 1, prostate‐specific antigen screening; group 2, non‐prostate‐specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank‐sum and χ²‐tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence‐free survival.

Results

In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate‐specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5‐year biochemical recurrence‐free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate‐specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate‐specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate‐specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study.

Conclusions

Detection by screening results in favorable outcomes after surgery. Prostate‐specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer.

     

中性粒细胞和淋巴细胞比值对根治性前列腺切除术患者生化复发的影响

目的探究接受根治性前列腺切除术治疗的患者,其中性粒细胞和淋巴细胞比值(NLR)与生化复发(BCR)的关系。方法回顾性收集2009年1月至2017年12月于四川大学华西医院接受根治性前列腺切除术(RP)的620例前列腺癌患者的临床资料。运用单因素与多因素Cox回归分析、限制性3次样条回归分析和趋势性检验分析NLR与BCR的关系,用分层分析进一步讨论手术入路、肿瘤大小和前列腺特异性抗原(PSA)水平对NLR与BCR关系的影响。结果术前升高的NLR不会导致BCR(P=0.31)。然而,亚组分析显示,在中等PSA水平组中,升高的NLR可导致BCR风险增加(HR=1.12,95%CI:1.04~1.20,P=0.04)。在经腹腔入路手术的患者中,较高的NLR更容易导致BCR(HR=1.05,95%CI:0.99~1.11,P=0.02)。对于那些肿瘤体积中等(HR=1.06,95%CI:0.93~1.20,P=0.03)或较大(HR=1.02,95%CI:0.94~1.10,P=0.03)的患者,BCR风险可随着NLR的升高而增加。结论对于经腹腔入路手术、肿瘤大小中等或较大、中等PSA水平的患者,生化复发风险与NLR呈正相关。     

Impact of a novel,extended approach of perineal radical prostatectomy on surgical margins in localized prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To validate the rationale of extended perineal radical prostatectomy (ePRP) for treating localized prostate cancer.

PATIENTS AND METHODS

Between December 2000 and May 2007, 196 patients with localized prostate cancer underwent PRP, among which 91 and 105 patients were treated with conventional PRP (cPRP) and ePRP, respectively. The apex, middle, base, and anterior regions of the prostate were separately analysed, and the focus of analysis was on the distribution, size, Gleason score, and positive surgical margins (PSMs) of prostate cancer foci.

RESULTS

The operation time was significantly shorter in ePRP compared with cPRP (161 min vs 188 min; P= 0.001), while there was no significant difference in estimated blood loss between cPRP and ePRP (550 mL vs 500 mL). At the apex and base, there was no significant difference in the PSM rate between cPRP and ePRP. In the middle, there was a lower incidence of PSMs in ePRP (2.4%) than in cPRP (10.9%; P= 0.009). On the anterior side, PSMs were more frequent in cPRP (21.6%) than in ePRP (7.1%; P= 0.029). Logistic regression analysis adjusted by PSA level showed that PSM rate was the most significantly affected by the surgical approach.

CONCLUSION

We think that ePRP provides an effective treatment strategy for localized prostate cancer in light of excellent cancer control and minimum potential of surgical invasiveness.     

A low incidence of positive surgical margins in prostate cancer at high risk of extracapsular extension after a modified anterograde radical prostatectomy

OBJECTIVES: To evaluate the incidence of positive surgical margins (and associated risk factors) in patients with localized prostate cancer at high preoperative risk of extracapsular disease treated using a modified anterograde radical retropubic prostatectomy technique. Positive surgical margins are an important risk factor for disease recurrence after radical prostatectomy, particularly in patients with extracapsular disease. PATIENTS AND METHODS: In total, 84 patients with clinically localized prostate cancer and a preoperative prostate-specific antigen (PSA) level > 10 ng/mL and/or a biopsy Gleason score > or = 7 were evaluated. The surgical technique allows easy, wide resection of the posterolateral prostatic pedicles, and good mobilization and exposure of the apex before the urethra transection. Prostatectomy specimens were examined for extracapsular tumour spread and positive surgical margins. Differences in putative risk factors (Gleason score, preoperative PSA level, prostate weight) between the positive- and negative-margin groups were evaluated using the Mann-Whitney test. RESULTS: Overall, 11 of the 84 (13%) patients had positive surgical margins and of these a single site was involved in six. In total, 15 positive-margin sites were identified (five apical, four basal, three posterolateral, two anterior and one posterior). All patients with positive margins had histological extracapsular disease. The preoperative PSA level and Gleason score were significantly higher in the positive- than in the negative-margin group (P = 0.025 and 0.035, respectively). CONCLUSIONS: The anterograde radical prostatectomy minimizes the incidence of positive surgical margins in patients at high risk of extracapsular disease.     

Lateral view dissection of the prostato-urethral junction to reduce positive apical margin in laparoscopic radical prostatectomy

Objective:   To assess the impact of lateral view apical dissection in laparoscopic radical prostatectomy (LRP) on the reduction of positive surgical margin rates and recovery of postoperative continence.
Methods:   One hundred and forty-four consecutive patients underwent LRP from October 2004 to March 2008. Lateral view dissection of the prostato-urethral junction was conducted in 76 of them (Group 2). Standard dissection was used in the remaining patients (Group 1). The effect of this technical modification on the reduction of positive surgical margin rates and postoperative recovery of urinary continence was assessed in the two groups.
Results:   Overall, the incidence of positive margins decreased from 23 (35.9%) in Group 1 to 16 cases (21.9%) in Group 2 ( P  = 0.07). Positive margin rates in pT2 decreased from 30.6% to 6.5% ( P  = 0.006). Apical and dorso-apical margins were reduced from 26.5% to 4.3% ( P  = 0.009) and from 10.2% to 0% ( P  < 0.001), respectively. Postoperative recovery of urinary continence improved significantly, with a pad-free rate over the first 3 months of 55.9% in Group 1 vs 71.7% in Group 2 ( P  = 0.01). Multivariate logistic regression analysis showed this modified surgical technique to predict a lower rate of positive margins.
Conclusion:   Lateral view dissection of the prostato-urethral junction is an easily applicable technical modification. It provides better visualization of apical anatomy substantially contributing to the reduction of positive surgical margin rates, especially at the level of prostatic apex.