Prognostic Significance of Tumor Volume in Radical Prostatectomy and Needle Biopsy Specimens

Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland 21231, USA.
The Journal of urology (Impact Factor: 4.47). 09/2011; 186(3):790-7. DOI: 10.1016/j.juro.2011.02.2695
Source: PubMed


This review addresses the controversies that persist relating to the prognosis and reporting of tumor volume in adenocarcinoma of the prostate.
A search was performed using the MEDLINE database and referenced lists of relevant studies to obtain articles addressing the quantification of cancer on radical prostatectomy and needle biopsy.
In the 2010 TNM classification system T2 tumor at radical prostatectomy is subdivided into pT2a (unilateral tumor occupying less than ½ a lobe), pT2b (unilateral tumor greater than ½ a lobe) and pT2c (bilateral tumor). This pathological substaging of T2 disease fails on several accounts. In most studies pT2b disease almost does not exist. By the time a tumor is so large that it microscopically occupies more than ½ a lobe, in the majority of cases there is bilateral (pT2c) tumor. An even greater flaw of the substaging system for stage pT2 disease is the lack of prognostic significance. In reporting pathologically organ confined cancer, it should be merely noted as pT2 without further subclassification. The data are conflicting as to the independent prognostic significance of objective measurements of tumor volume in radical prostatectomy specimens. The most likely explanation for the discordant results lies in the strong correlation of tumor volume with other prognostic markers such as extraprostatic extension and positive margins. In studies where it is statistically significant on multivariate analysis, it is unlikely that knowing tumor volume improves prediction of prognosis beyond routinely reported parameters to the degree that it would be clinically useful for an individual patient. An alternative is to record tumor volume as minimal, moderate or extensive, which gives some indication to the urologist as to the extent of disease. Not only does providing an objective measurement not add useful prognostic information beyond what is otherwise routinely reported by the pathologist, but many objective measurements done in routine practice will likely not be an accurate indicator of the true tumor volume. There is also a lack of consensus regarding the best method of measuring tumor length when there are multiple foci in a single core separated by benign intervening prostatic stroma. Some pathologists, this author included, consider discontinuous foci of cancer as if it was 1 uninterrupted focus, the rationale being that these discontinuous foci are undoubtedly the same cancer going in and out of the plane of section. Measuring the cancer from where it starts to where it ends on the core gives the minimal length of cancer in the prostate. Others measure each focus individually, and the sum of these measurements is considered the cancer length on the core. Quantifying cancer with an ocular micrometer to record the total length or percent length of cancer is time-consuming, and the data are conflicting whether this is superior to other, simpler methods and whether any potential differences in predictive accuracy would translate into changes in clinical management. It is recommended that at a minimum the number of positive cores be recorded, unless fragmented involved cores preclude evaluation, along with at least 1 other more detailed measurement such as the percent of core involvement or length of cancer.
Consensus has been reached on some of the issues relating to quantifying tumor volume in prostate cancer, such as the lack of utility of substaging pT2 disease. Other questions such as whether to include or subtract intervening benign prostate tissue on prostate needle cores will require additional studies. Finally, matters such as the need to quantify cancer at radical prostatectomy or which method of quantifying cancer on needle biopsy is superior will likely remain contentious due to the close interrelationship and redundancy of prognostic variables.

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    • "User-friendly predictive tools like look-up tables, risk classifications and nomograms have been developed [11,13]. Some variables like lymphovascular invasion [14], tumor volume [15], pT2 subclassification [16] and tertiary Gleason grade [17] are conflicting or have insufficient supporting data yet. "
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    ABSTRACT: Background Prostate cancer is the most common male malignancy and a mayor cause of mortality in the western world. The impact of clinicopathological variables on disease related outcomes have mainly been reported from a few large US series, most of them not reporting on perineural infiltration. We therefore wanted to investigate relevant cancer outcomes in patients undergoing radical prostatectomy in two Norwegian health regions with an emphasis on the impact of perineural infiltration (PNI) and prostate specific antigen- doubling time (PSA-DT). Methods We conducted a retrospective analysis of 535 prostatectomy patients at three hospitals between 1995 and 2005 estimating biochemical failure- (BFFS), clinical failure- (CFFS) and prostate cancer death-free survival (PCDFS) with the Kaplan-Meier method. We investigated clinicopathological factors influencing risk of events using cox proportional hazard regression. Results After a median follow-up of 89 months, 170 patients (32%) experienced biochemical failure (BF), 36 (7%) experienced clinical failure and 15 (3%) had died of prostate cancer. pT-Stage (p = 0.001), preoperative PSA (p = 0.047), Gleason Score (p = 0.032), non-apical positive surgical margins (PSM) (p = 0.003) and apical PSM (p = 0.031) were all independently associated to BFFS. Gleason score (p = 0.019), PNI (p = 0.012) and non-apical PSM (p = 0.002) were all independently associated to CFFS while only PNI (P = 0.047) and subgroups of Gleason score were independently associated to PCDFS. After BF, patients with a shorter PSA-DT had independent and significant worse event-free survivals than patients with PSA-DT > 15 months (PSA-DT = 3-9 months, CFFS HR = 6.44, p < 0.001, PCDFS HR = 13.7, p = 0.020; PSA-DT < 3 months, CFFS HR = 11.2, p < 0.001, PCDFS HR = 27.5, p = 0.006). Conclusions After prostatectomy, CFFS and PCDFS are variable, but both are strongly associated to Gleason score and PNI. In patients with BF, PSA-DT was most strongly associated to CF and PCD. Our study adds weight to the importance of PSA-DT and re-launches PNI as a strong prognosticator for clinically relevant endpoints.
    BMC Urology 06/2014; 14(1):49. DOI:10.1186/1471-2490-14-49 · 1.41 Impact Factor
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    • "No preoperative factors were found to be predictive. It has long been known that PCA tumor volume correlates well with common adverse features such as high Gleason score, extraprostatic extension, seminal vesicle invasion, and clinical outcome [24] [25]. However, in the current study, a positive biopsy from the apex was not predicted by PSA level, Gleason score, stage, or total tumor volume, but only by the apex tumor volume. "
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    ABSTRACT: Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transrectal biopsy approach, especially for presurgical detection of cancer in the prostatic apex. Materials and Methods. From 2006 to 2011, 158 patients whose radical prostatectomy specimens had been evaluated were retrospectively enrolled in this study. Concordance rates for histopathology results of prostatectomy specimens and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle, base, and transitional zones bilaterally) from 73 patients diagnosed at this institution, besides factors for detecting apex cancer in total 118 true positive and false negative apex cancers. Results. Prostate cancer was found most frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153 (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No readily available preoperative factors for detecting apex cancer were identified. Conclusions. In Japanese patients, the most frequent location of prostate cancer is in the apex. There is a high false negative rate for transrectal biopsy samples. To improve the detection rate, transperitoneal biopsy or more accurate imaging technology is needed.
    02/2013; 2013:705865. DOI:10.1155/2013/705865
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    • "Features widely used to indicate high risk include Gleason score !7, as well as parameters to indicate the extent of cancer such as maximum cancer core length (MCCL), maximum percentage cancer, and the number of positive biopsies [6]. However, if a tumour is exposed to a greater sampling density than the rest of the prostate, it is likely that the proportion of cores that are positive and the MCCL will be greater compared with a TRUS biopsy. "
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    ABSTRACT: BACKGROUND: Prostate biopsy parameters are commonly used to attribute cancer risk. A targeted approach to lesions found on imaging may have an impact on the risk attribution given to a man. OBJECTIVE: To evaluate whether, based on computer simulation, targeting of lesions during biopsy results in reclassification of cancer risk when compared with transrectal ultrasound (TRUS) guided biopsy. DESIGN, SETTING, AND PARTICIPANTS: A total of 107 reconstructed three-dimensional models of whole-mount radical prostatectomy specimens were used for computer simulations. Systematic 12-core TRUS biopsy was compared with transperineal targeted biopsies using between one and five cores. All biopsy strategies incorporated operator and needle deflection error. A target was defined as any lesion ≥0.2ml. A false-positive magnetic resonance imaging identification rate of 34% was applied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity was calculated for the detection of all cancer and clinically significant disease. Cases were designated as high risk based on achieving ≥6mm cancer length and/or ≥50% positive cores. Statistical significance (p values) was calculated using both a paired Kolmogorov-Smirnov test and the t test. RESULTS AND LIMITATIONS: When applying a widely used biopsy criteria to designate risk, 12-core TRUS biopsy classified only 24% (20 of 85) of clinically significant cases as high risk, compared with 74% (63 of 85) of cases using 4 targeted cores. The targeted strategy reported a significantly higher proportion of positive cores (44% vs 11%; p<0.0001) and a significantly greater mean maximum cancer core length (7.8mm vs 4.3mm; p<0.0001) when compared with 12-core TRUS biopsy. Computer simulations may not reflect the sources of errors encountered in clinical practice. To mitigate this we incorporated all known major sources of error to maximise clinical relevance. CONCLUSIONS: Image-targeted biopsy results in an increase in risk attribution if traditional criteria, based on cancer core length and the proportion of positive cores, are applied. Targeted biopsy strategies will require new risk stratification models that account for the increased likelihood of sampling the tumour.
    European Urology 01/2013; 65(3). DOI:10.1016/j.eururo.2012.12.057 · 13.94 Impact Factor
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