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.     

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.     

The outcome of patients with pathological Gleason score >or=8 prostate cancer after radical prostatectomy

OBJECTIVE

To analyse the outcome of patients undergoing radical prostatectomy (RP) for Gleason 8–10 clinically localized prostate cancer, and to evaluate the prognostic value of well‐known predictors of progression.

PATIENTS AND METHODS

In all, 1480 patients had RP between 1988 and 2006, of whom 180 had pathological Gleason score ≥8 and negative lymph nodes. Biochemical progression‐free survival was determined using the Kaplan‐Meier method. The effect of preoperative prostate‐specific antigen (PSA) level, pathological stage and margin status was assessed with univariate and multivariate analyses.

RESULTS

Of the 180 patients, the Gleason score in the RP specimen was 8, 9 or 10 in 70%, 27% and 3%, respectively; 24% had stage pT2 disease, 30% stage pT3a, 25% stage pT3b and 20% stage pT4a. The 5‐ and 7‐year biochemical progression‐free survival was 73 and 65% for stage pT2, 40% and 27% for stage pT3a, and 30% for stage pT3b (log rank test, P < 0.001). In the univariate model, preoperative PSA level, pathological stage and surgical margins were predictors of survival. In the multivariate analysis, preoperative PSA level and extracapsular extension predicted biochemical progression‐free survival.

CONCLUSION

Gleason 8–10 tumours have a poor prognosis. Patients with a PSA level of <10 ng/mL and stage pT2 disease have the greatest likelihood of having a longer progression‐free survival after RP.     

Comparison of Gleason grade and score between preoperative biopsy and prostatectomy specimens in prostate cancer

AIM: Although the histopathological findings obtained from biopsy specimens are important for choosing the appropriate management of prostate cancer, there have been some discrepancies in Gleason grade and consequently, score between biopsy and surgical specimens. A comparison of findings between these two kinds of specimens was performed. METHODS: Radical prostatectomy was performed at Asahi General Hospital on 223 cases of T1b-T3 without previous cancer treatment, and the Gleason grade and score of the biopsy and surgical specimens were compared. RESULTS: A 37% coincidence in Gleason score was obtained between biopsy and surgical specimens; coincidence including one digit difference in score was approximately 70%. Upgrading was more than downgrading. Disagreement in secondary grade was greater than that in primary grade. Disagreement in Gleason score was roughly similar among different score items and was not influenced by level of prostate-specific antigen, however, the small volume of the cancer tissues more affected the discrepancy in score. CONCLUSION: The use of biopsy findings is required to be taken into account regarding the discrepancy.     

Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: contemporary approach, current clinical significance and sources of pathology discrepancies

The Gleason grading system is a powerful tool to prognosticate and aid in the treatment of men with prostate cancer. The needle biopsy Gleason score correlates with virtually all other pathological variables, including tumour volume and margin status in radical prostatectomy specimens, serum prostate-specific antigen levels and many molecular markers. The Gleason score assigned to the tumour at radical prostatectomy is the most powerful predictor of progression after radical prostatectomy. However, there are significant deficiencies in the practice of this grading system. Not only are there problems among practising pathologists but also a relative lack of interobserver reproducibility among experts.     

How accurately does prostate biopsy Gleason score predict pathologic findings and disease free survival?

OBJECTIVE: Due to the significant impact on prognosis by subgrouping of prostatectomy Gleason scores < 7, 7, and > 7, we undertook this study to answer whether the biopsy Gleason score was as predictive of disease free survival and assess the correlation with the prostatectomy Gleason score in a modern prostatectomy series. METHODS: An analysis of 1,031 patients who underwent radical prostatectomy for clinically localized prostate cancer was performed. All data was prospectively collected. The Gleason score was categorized into 3 different groups (< 7, 7, and > 7) for biopsy and prostatectomy specimens. Disease free survival was then analyzed for each group. Discrepancies between scores and outcomes were evaluated. RESULTS: Accurate correlation was noted in 54.8, 66.8, and 47.4% of Gleason scores < 7, 7, and > 7, respectively. Overall accuracy was 58.3%. Both, biopsy and prostatectomy Gleason score correlated significantly with disease free survival (P = 0.001), furthermore the classification (Gleason scores < 7, 7 and > 7) was highly significant (P = 0.001). Patients with prostatectomy Gleason < 7 tumors had significant survival advantage over those with biopsy Gleason < 7, (P = 0.001). However, disease free survival was superior for patients with biopsy Gleason > 7 than those with prostatectomy Gleason > 7, (P = 0.02). The overall disease free survival was similar among the patients with Gleason score of 7 (P = 0.12). CONCLUSIONS: It appears that biopsy Gleason score, although oftentimes not correlating strongly with the prostatectomy Gleason score, is an important prognostic factor in prostate cancer. There are significant differences in disease free survival between biopsy and prostatectomy Gleason score categories.     

Impact of prostate-specific antigen testing on the clinical and pathological outcomes after radical prostatectomy for Gleason 8-10 cancers

OBJECTIVE

To investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate‐specific antigen (PSA) testing for patients with Gleason 8–10 cancers.

PATIENTS AND METHODS

We identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8–10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988–93), mid (1994–97) and late PSA era (1998–2001). Survival rates after RRP were estimated using the Kaplan‐Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models.

RESULTS

The median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era (P < 0.001), while the rate of organ‐confined disease increased from 22.9% to 35.1% (P = 0.007). However, the 7‐year biochemical recurrence‐free (37% vs 45%, P = 0.087) and cancer‐specific survival (89% to 91%, P = 0.73) did not change significantly from the early to the late PSA era. Increased preoperative PSA level (P < 0.001), seminal vesicle invasion (P < 0.001) and positive lymph nodes (P = 0.02) were associated with biochemical recurrence. Seminal vesicle invasion (P = 0.005), positive nodes (P < 0.001) and positive surgical margins (P = 0.03) predicted death from cancer.

CONCLUSION

Although the pathological features of Gleason 8–10 cancers have become more favourable over the PSA era, survival has not changed. This lack of improvement in clinical outcome probably reflects the inherent biological aggressiveness of these cancers. While RRP provides long‐term cancer control in a subset of these patients, continued investigation of multi‐modal treatment options is warranted.     

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.     

Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients

OBJECTIVE: To assess the association between surgical volume (SV) and the rate of positive surgical margins (PSM) after radical prostatectomy (RP) in a large single-institution European cohort of patients. PATIENTS AND METHODS: In all, 2402 men had a RP by a group of 11 surgeons, all of whom were trained by the surgeon with the highest SV; all surgeons used the same surgical technique. Variables assessed before RP were prostate-specific antigen (PSA) level, clinical stage and biopsy Gleason sum; variables assessed after RP were PSA level, extracapsular extension, seminal vesicle invasion, lymph node invasion and pathological Gleason sum. These were used to predict the rate of PSM in models before or after RP. Multivariate models were complemented with SV to test its independent and multivariate statistical significance and to quantify its impact on the model's overall (and 200 bootstrap-corrected) predictive accuracy. RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly statistically significant independent predictor of PSM (P < 0.001) and increased the predictive accuracy in multivariate models both before (2.0%) and after RP (1.5%, both P < 0.001). However, when the surgeon with the highest SV, who contributed to 1293 cases, was removed from the analyses, the multivariate independent prediction and the gains in predictive accuracy related to adding SV, disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P = 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that patients treated by surgeons with a very high volume can expect to have a significantly lower rate of PSM, after accounting for clinical and pathological case-mix differences. However, SV is not a predictor of PSM when analyses are restricted to intermediate- and low-volume surgeons.