The Contemporary Concept of Significant Versus Insignificant Prostate Cancer

Department of Urology, Saint-Louis Hospital, APHP, Paris, France.
European Urology (Impact Factor: 13.94). 08/2011; 60(2):291-303. DOI: 10.1016/j.eururo.2011.05.006
Source: PubMed


The notion of insignificant prostate cancer (Ins-PCa) has progressively emerged in the past two decades. The clinical relevance of such a definition was based on the fact that low-grade, small-volume, and organ-confined prostate cancer (PCa) may be indolent and unlikely to progress to biologic significance in the absence of treatment.
To review the definition of Ins-PCa, its incidence, and the clinical impact of Ins-PCa on the contemporary management of PCa.
A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction on language up to September 2010. The literature search used the following terms: insignificant, indolent, minute, microfocal, minimal, low volume, low risk, and prostate cancer.
The most commonly used criteria to define Ins-PCa are based on the pathologic assessment of the radical prostatectomy specimen: (1) Gleason score ≤ 6 without Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumour volume<0.5 cm(3). Several preoperative criteria and prognostication tools for predicting Ins-PCa have been suggested. Nomograms are best placed to estimate the risk of progression on an individualised basis, but a substantial proportion of men with a high probability of harbouring Ins-PCa are at risk for pathologic understaging and/or undergrading. Thus, there is an ongoing need for identifying novel and more accurate predictors of Ins-PCa to improve the distinction between insignificant versus significant disease and thus to promote the adequate management of PCa patients at low risk for progression.
The exciting challenge of obtaining the pretreatment diagnostic tools that can really distinguish insignificant from significant PCa should be one of the main objectives of urologists in the following years to decrease the risk of overtreatment of Ins-PCa.

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    • "The aim of the study was to asses how many patients could be qualified for focal therapy, according to the post prostatectomy anatomopathological findings. In our study, eighty one consecutive patients treated by prostatectomy were enrolled according to the Epstein criteria [8, 9]. Of those, 10% were unifocal and 90% presented with multifocal disease for which focal therapy is not possible. "
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    ABSTRACT: Introduction The main treatment methods of prostate carcinoma are surgery and radiation therapy, both having serious side effects. Because of these side effects, the idea of organ preserving therapy emerged. Rationale to perform focal therapy is to preserve the prostate gland, along with potency and continence, offering good cancer control with appropriate treatment. The idea of gland sparing therapy is quite controversial. Presently, EAU Guidelines propose focal therapy as experimental in the treatment of prostate carcinoma. Material and methods The aim of the study was to asses how many patients could be qualified for focal therapy, according to post prostatectomy pathological findings. 720 patients suspected of prostate cancer were biopsied. In 324 patients, prostate carcinoma was revealed, of which 81 were subjected to radical prostatectomy. Pre and post–operative pathological results were analyzed, according to possible qualification for focal treatment. Results According to the clinical evaluation of all the patients referred to the treatment, 25% could be assumed to have unifocal disease and could be qualified to the focal treatment. Post–operative evaluation revealed pT2b cancer in 5%, pT2c disease in 65%, and pT3a–pT4a disease in 20% of these patients. Cancer was unilateral (pT2a–b) in only 15% of cases, and was suitable for focal treatment (small disease not extending to whole lobe– pT2a disease) in only 10%. Conclusions It seems that with the use of current methods, proper T–staging of the disease and amount of neoplasmatic tissue inside the gland can not be reached with great certainty. In our opinion, focal therapy should not be used in patients with ≤pT2b and high risk disease. For them, radical treatment (surgery or radiation therapy) should be recommended. For the rest of the patients, with low risk disease, keeping in mind the large scale of possible overtreatment, active surveillance is a valid treatment option. Focal therapy can be an interesting therapeutic proposition for a small group of patients with pT2a cancer, but it is not possible to select them with big certainty with current methods of imaging medicine.
    Full-text · Article · Aug 2014
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    • "Urologists commonly use the classical definition of insignificant prostate cancer (IPC), which describes cases as organ-confined, Gleason 6 disease with tumor volume (TV) <0.5 mL [1]. The TV threshold of this definition was suggested by Stamey et al. [2], who used a cystoprostatectomy study. "
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    ABSTRACT: Purpose: We compared oncological outcomes according to tumor volume (TV) thresholds defining both classical and updated insignificant prostate cancer (IPC), since the TV threshold can be used as clinical parameter for active surveillance. Methods: Between 2001 and 2012, we retrospectively analyzed 331 organ-confined prostate cancer patients who had preoperative Gleason score 6, preoperative PSA under 10 ng/mL and pathologic TV less than 1.3 mL. Among them, 81 of 331 (24.5%) had Gleason grade 4/5 disease postoperatively. Patients were stratified into two groups: (1) TV less than 0.5 mL, using the classical definition; and (2) TV between 0.5 mL and 1.3 mL, using the range of updated definition. We compared biochemical recurrence (BCR)-free survival and identified independent predictors of BCR in each group. Results: Group 2 had more Gleason grade 4/5 disease than group 1 (P<0.001). On multivariate analysis, Gleason grade 4/5 disease was not associated with BCR in group 1 (P=0.132). However, it was an independent predictor for BCR in group 2 (P=0.042). BCR-free survival were not significantly different according to the presence of Gleason grade 4/5 disease in group 1 (P=0.115). However, in group 2, it was significantly different according to the presence of Gleason grade 4/5 disease (P=0.041). Conclusions: Although the TV thresholds of the two definitions of IPC vary only slightly, this difference was enough to result in different clinical course if Gleason grade 4/5 disease was present. Therefore, the updated IPC TV threshold should be carefully applied as clinical parameter for active surveillance.
    Full-text · Article · Jun 2014
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    • "At time of diagnosis, Gleason score has been shown to be a strong predictor of high risk PC [42], but also metastasis and PCD after RP [38,43]. Including all patients in the analyses we consistently found patients with a Gleason sum ≥9 to have the highest risk of BF (equal to pT3b), CF and PCD. "
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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.
    Full-text · Article · Jun 2014 · BMC Urology
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