The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomy

OBJECTIVES

To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate‐specific antigen (PSA)‐failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP).

PATIENTS AND METHODS

We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis.

RESULTS

The median (range) MTL was 4 (0.2–19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic‐failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow‐up after surgery was 90 (17–152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer.

CONCLUSIONS

The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies.     

Accuracy of transrectal ultrasound guided prostate biopsy: Histopathological correlation to matched prostatectomy specimens

BACKGROUND: The Gleason grading system is currently the world's most commonly used histological system for prostate cancer. It provides significant information about the prognosis. Therefore, Gleason score is accepted as an important factor in therapeutic decision-making for prostate cancer. This retrospective study assessed the correlation of transrectal ultrasound (TRUS) guided biopsy and radical prostatectomy specimens in terms of Gleason scores. METHODS: We reviewed the records of 103 patients who underwent radical prostatectomy due to clinically localized prostate cancer. The Gleason scores of the TRUS biopsies were compared with the respective Gleason scores of surgical specimen. RESULTS: In 28.7% of cases, the TRUS biopsy score was the same as that of the radical prostatectomy specimen. The most significant discordance was the upgrading of well-differentiated tumors after surgery in 71.7% of cases. However, in 81.8% of cases with high Gleason score on TRUS, biopsy was correlated with poorly differentiated tumor after surgery. CONCLUSIONS: Well-differentiated tumors on TRUS biopsy did not correlate with the grades of final pathology in the majority of cases; however, a high Gleason score on TRUS biopsy usually indicated a poorly differentiated tumor on prostatectomy specimen. Therefore, the treatment algorithms for particularly well-differentiated tumors should not be deduced from biopsy histology alone.     

The total percentage of biopsy cores with cancer improves the prediction of pathological stage after radical prostatectomy

OBJECTIVE: To examine whether the simple variable 'percentage of cancer-positive biopsy cores' is a significant predictor of true pathological stage after radical prostatectomy and can be used to improve pathological stage prediction by simple means. PATIENTS AND METHODS: In all, 375 patients had a radical prostatectomy for localized prostate cancer in two UK centres; 260 had complete preoperative staging information. Logistic regression was used and predicted probability graphs constructed to assess predictors of pathological stage. RESULTS: In this study, only PSA (P = 0.004) and percentage cancer-positive biopsy cores (P < 0.001) were significant predictors of pathological stage. The final model was an acceptable classifier for pathological stage (area under the receiver operating characteristic curve 0.76, specificity 85%, sensitivity 47%). A patient with a PSA of 10 ng/mL and one of six cores positive for cancer would have a predicted probability of extraprostatic disease of 20%, whereas the same patient with all six biopsy cores positive would have a predicted probability of extraprostatic disease of 80%. CONCLUSIONS: The percentage of cancer-positive biopsy cores significantly predicts the disease stage after radical prostatectomy. This variable is easy to obtain by the clinician and avoids the need to estimate the percentage of biopsy tissue infiltrated by cancer. This readily available information can easily be computed and may help to counsel patients about realistic expectations of organ-confined disease in relation to surgery as a treatment option.     

The presence of prostate cancer on saturation biopsy can be accurately predicted

Study Type – Diagnostic (non‐consecutive)
Level of Evidence 3b

OBJECTIVE

To improve the ability of our previously reported saturation biopsy nomogram quantifying the risk of prostate cancer, as the use of office‐based saturation biopsy has increased.

PATIENTS AND METHODS

Saturation biopsies of 540 men with one or more previously negative 6–12 core biopsies were used to develop a multivariable logistic regression model‐based nomogram, predicting the probability of prostate cancer. Candidate predictors were used in their original or stratified format, and consisted of age, total prostate‐specific antigen (PSA) level, percentage free PSA (%fPSA), gland volume, findings on a digital rectal examination, cumulative number of previous biopsy sessions, presence of high‐grade prostatic intraepithelial neoplasia on any previous biopsy, and presence of atypical small acinar proliferation (ASAP) on any previous biopsy. Two hundred bootstraps re‐samples were used to adjust for overfit bias.

RESULTS

Prostate cancer was diagnosed in 39.4% of saturation biopsies. Age, total PSA, %fPSA, gland volume, number of previous biopsies, and presence of ASAP at any previous biopsy were independent predictors for prostate cancer (all P < 0.05). The nomogram was 77.2% accurate and had a virtually perfect correlation between predicted and observed rates of prostate cancer.

CONCLUSIONS

We improved the accuracy of the saturation biopsy nomogram from 72% to 77%; it relies on three previously included variables, i.e. age, %fPSA and prostate volume, and on three previously excluded variables, i.e. PSA, the number of previous biopsy sessions, and evidence of ASAP on previous biopsy. Our study represents the largest series of saturation biopsies to date.     

A biopsy simulation study to assess the accuracy of several transrectal ultrasonography (TRUS)-biopsy strategies compared with template prostate mapping biopsies in patients who have undergone radical prostatectomy

Study Type – Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Transrectal ultrasonography (TRUS)‐guided biopsies can miss prostate cancer and misclassify risk in a diagnostic setting; the exact extent to which it does so in a repeat biopsy strategy in men with low–intermediate risk prostate cancer is unknown. A simulation study of different biopsy strategies showed that repeat 12‐core TRUS biopsy performs poorly. Adding anterior sampling improves on this but the highest accuracy is achieved using transperineal template prostate mapping using a 5 mm sampling frame.

OBJECTIVE

• ? To determine the effectiveness of two sampling strategies; repeat transrectal ultrasonography (TRUS)‐biopsy and transperineal template prostate mapping (TPM) to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL using computer simulation on reconstructed three‐dimensional (3‐D) computer models of radical whole‐mount specimens.

PATIENTS AND METHODS

• ? Computer simulation on reconstructed 3‐D computer models of radical whole‐mount specimens was used to evaluate the performance characteristics of repeat TRUS‐biopsy and TPM to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL.
• ? In all, 107 consecutive cases were analysed (1999–2001) with simulations repeated 500 times for each biopsy strategy.
• ? TPM and five different TRUS‐biopsy strategies were simulated; the latter involved a standard 12‐core sampling and incorporated variable amounts of error, as well as the addition of anterior cores.
• ? Sensitivity, specificity, negative and positive predictive values for detection of lesions with a volume of ≥0.2 mL or ≥0.5 mL were calculated.

RESULTS

• ? The mean (sd ) age and PSA concentration were 61 (6.4) years and 8.5 (5.9) ng/mL, respectively.In all, 53% (57/107) had low–intermediate risk disease.
• ? In all, 665 foci were reconstructed; there were 149 foci ≥0.2 mL and 97 ≥ 0.5 mL in the full cohort and 68 ≥ 0.2 mL and 43 ≥ 0.5 mL in the low–intermediate risk group.
• ? Overall, TPM accuracy (area under the receiver operating curve, AUC) was ≈0.90 compared with AUC 0.70–0.80 for TRUS‐biopsy.
• ? In addition, at best, TRUS‐biopsy missed 30–40% of lesions of ≥0.2 mL and ≥0.5 mL whilst TPM missed 5% of such lesions.

CONCLUSION

• ? TPM under simulation conditions appears the most effective re‐classification strategy, although augmented TRUS‐biopsy techniques are better than standard TRUS‐biopsy.

     

Cancer ablation with regional templates applied to prostatectomy specimens from men who were eligible for focal therapy

OBJECTIVE

To assess the totality of prostate cancer eradication in radical prostatectomy (RP) specimens from men with a unilaterally positive prostate biopsy, and who would currently qualify for subtotal prostate ablation with controlled thermal energy such as cryoablation or high‐intensity focused ultrasound.

MATERIALS AND METHODS

Therapies for prostate cancer hold the promise of individualized treatment that selectively ablates the tumour while minimizing treatment‐associated morbidity, but as prostate cancer is multifocal there are concerns about untreated residual disease. RP specimens (180) from men with a unilaterally positive prostate biopsy were examined to characterize the location, volume and grade of each tumour focus. Two treatment templates (hemiprostate and ‘hockey‐stick’) were applied to every prostate cross‐section. The nature of the in‐field and out‐of‐field tumours was assessed and described for each treatment template.

RESULTS

A single focus of cancer was the only tumour in 31 (17%) of the patients (contralateral cancer was present in 149, 83%, of specimens despite a unilateral positive biopsy). Hemiprostate and hockey‐stick treatment templates covered all tumour foci in 17% and 47% of men, respectively. Most out‐of‐field cancers were clinically insignificant tumours not identified by prostate biopsy (low‐volume, 0.5 mL; and low grade, Gleason score ≤6). Regional ablation would have successfully treated all clinically significant prostate tumours in 64% and 81% of patients using the hemiprostate or hockey‐stick template, respectively. The hockey‐stick template encompassed all dominant tumours (largest volume).

CONCLUSIONS

Regionally targeted prostate ablation is capable of eradicating all dominant tumours and the vast majority of clinically significant tumours in men with unilateral disease by biopsy. The study of focally ablative therapy should proceed under the auspices of an approved protocol.     

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.     

Six additional systematic lateral cores enhance sextant biopsy prediction of pathological features at radical prostatectomy

PURPOSE: We evaluated the contribution of 6 additional systematically obtained, laterally directed biopsy cores to traditional sextant biopsy for the prediction of final pathological findings in the radical prostatectomy specimen. MATERIALS AND METHODS: We studied 178 consecutive patients with no history of prostate biopsy in whom prostate cancer was diagnosed during an initial systematic 12 core biopsy and who subsequently underwent radical prostatectomy. Of the systematic 12 cores we compared the subset of the 6 traditional sextant cores (S6C), the set of 6 laterally directed cores (L6C) and the complete 12 core set, which included the 6 traditional sextant and the 6 laterally directed cores. Biopsy Gleason score, number of positive cores, total cancer length and percent of tumor in the biopsy sets were examined for their ability to predict extracapsular extension, total tumor volume and pathological Gleason score. RESULTS: On univariable analyses the biopsy parameters of the complete 12 core set correlated more strongly with extracapsular extension and total tumor volume than the biopsy parameters of S6C or L6C. On multivariable analyses S6C and L6C were independent predictors of pathological features at prostatectomy. CONCLUSIONS: The addition of 6 systematically obtained, laterally directed cores to traditional sextant biopsy improved the ability to predict pathological features at prostatectomy by a statistically and prognostically significant margin. Preoperative nomograms that use data from a full complement of 12 systematic cores, specifying sextant and laterally directed biopsy cores, should demonstrate improved performance in predicting prostatectomy pathology.     

Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy

Salvage radical prostatectomy is considered for patients with locally recurrent prostate cancer after external beam radiotherapy. Between 2001 and 2004, 32 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. We assessed the morbidity associated with this procedure and the outcome of the patients. Thirty-two patients underwent salvage radical prostatectomy. Initial pre-radiation median prostate-specific antigen was 13 ng/ml. Pre-radiation disease was clinical stage T1b in five cases, T2a in 10, T2b in 10 and T3a in seven. Mean operative time was 122 minutes, intraoperative blood loss was 550 ml and hospital stay and catheterization time were 5 and 12 days, respectively. There was biochemical failure in eight patients after salvage radical prostatectomy and 24 patients are biochemical non evidence of disease (bNED). In recurrent prostate local disease with prostate-specific antigen <10 ng/ml and life expectancy greater than 10 years, salvage radical prostatectomy is a reasonable treatment option.