Prostate cancer is a multifocal and histologically heterogeneous disease.
[Shariat SF, Scardino PT, Lilja H, 2008:
[Receiver Operating Characteristics (ROC) and verification bias for test on prostate cancer using the total prostate specific antigen (tPSA) concentration as test parameter. Reference standard: biopsy. more PSA-ROCs, including proteom analysis by DiaPat)] click on figure to get an explanation of this set of ROCs
The numbers in boxes are the PSA threshold values ("test threshold") in ng/mL The sensitivity (= true positives, expressed as fraction of men with cancer) and 1 - specificity (= false positives, expressed as fraction of healthy men) of a screening test are biased when disease status is not verified in all subjects and when the likelihood of confirmation depends on the test result itself (details). Adjustment for verification bias significantly increased the area under the ROC curve (i.e., the overall diagnostic performance) of the PSA test, as compared with an unadjusted analysis (Punglia et al., 2003) [By means of clarification of ROC]
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Curves (DRE FAMHIST =) 0 0, 0 1, 1 0, 1 1
Prostate Cancer Risk = 1 / [1 + exp(-PCA)]
Symbols
Curve P is derived from lognormal distributions f of tPSA
Fig. ANN Performance: Performance at high tPSA of Artificial Neuronal Network with tPSA test kits from 5 manufacturers (click on figure to see performance at low tPSA)
Figure "Biopsy-detectable":
Risk of biopsy-detectable prostate cancer. (Source: University of Texas Health Science Center at San Antonio)
Definition of "Prostate Cancer Risk": Take a random sample of 100 men with the characteristics (tPSA, DRE, FAMHIST, PRIORBIOP). "Prostate Cancer Risk" = number of men having Pca in this sample divided by 100. "Prostate Cancer Risk" is calculated from the following nomogram:
with
PCA = -1.7968 + 0.8488 * log(tPSA) - 0.4483 * PRIORBIOP + 0.9054 * DRE + 0.2693 * FAMHIST
Note: This nomogram based calculator is only applicable for persons without a previous diagnosis of prostate cancer.
The numbers on the curves specify DRE (left number) and FAMHIST (right number).
Source: Risikoabschätzung für Prostatakrebs, Artifizielles Neuronales Netz (ANN), Charite - Universitätsmedizin Berlin, ProstataClass HCS 2008/4.2
Estimates suggest that with a threshold PSA value of 4.1 ng/mL,
Review: OW Brawley, DP Ankerst, IM Thompson, "Screening For Prostate Cancer" (in cache)
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[For localization of prostate cancer MRI and MRSI were more sensitive but less specific than biopsy (Wefer et al. 2000):The sensitivity of sextant biopsy was significantly less
- 67% (sensitivity MRI) and 76% (sensitivity MRSI) versus 50% (sensitivity biopsy), and
- 69% (specificity MRI) and 68% (specificity MRSI) versus 82% (specificity biopsy).
- in the prostate apex (38%) than
- in the mid prostate (52%) or
- in the prostate base (62%).]
In other studies,
[54% of 70 ten-core biopsy negative prostate hemispheres turned out to harbor up to 8 foci of cancer in the biopsy-negative hemisphere, of which 8 (11% of 70) were clinically significant and the remaining 30 clinically minor (Park PC et al. BJU Int. 2006 Nov;98(5):986-8, in cache)]. |
[Morphometric analysis on 70 biopsy-negative prostate hemispheres] Pca = prostatic adenocarcinoma, AH = anterior horn of the peripheral zone, TZ = transitional zone, NTZ = nontransitional zone, PZ = peripheral zone, sig = clinically significant, nsig = clinically insignificant |
Disregarding their sensitivity and specificity, what do biopsies come up with? (GC Durkan et al. 2002 - in cache, annotations)
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493 patients with elevated PSA |
Therefore, the need to improve both tumor detection and assessment of tumor aggressiveness is compelling.
[Fine needle aspiration biopsy DNA ploidy status predicts grade shifting in prostate cancer (Ross et al. 1999).
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Comparison of the detection of high-grade tumors by core needle biopsy histopathological (Gleason) grading and fine needle aspiration biopsy DNA ploidy analysis |
The combined use of MR imaging and MR spectroscopy
MRI versus biopsy: Sensitivities and specificities.
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Comparison of the MRI- and the MRI/MRSI models with two models that use a combination of the following test parameters (reference standard for all models: whole mount prostate step section pathology)
The MRI and the MRI/MRSI models take into account 6 test parameters:
Patient characteristics: For comparison: AUC for pure MRI and MRSI with biopsy as reference standard: 0.70 and 0.63, respectively (Costouros et al, 2007) |
Because Gleason grade is an important predictor of patient outcome, this finding provides a rationale for adding MR imaging and/or MR spectroscopy to the pretreatment evaluation of patients with prostate cancer.
[Further Literature, mostly on MR(S)I]
T Primary Tumor M Distant Metastases
Almost two thirds of PCa found were at stage T1 or T2 and would have been suitable for active surveillance [Bandemer-Greulich U, Wulff V, Marquaß S, Kindt B, "7.16 Prostatakarzinome (C61)" in Qualitätsbericht Onkologie 2009, Tumorzentrum Land Brandenburg e.V. und Qualitätskonferenz Onkologie (QKO), 2009 (in cache)].
There are no more precise data from Germany that show how many patients have a low risk PCa and would therefore be suitable to undergo active surveillance. Currently the best data source on PCa is the longitudinal data collection of CaPSURE. Of more than 10 000 patients included between 1989 and 2003,
These data give rise to the assumption that in Germany, the 69% of prostatectomies in men younger than 70 include many cases with an excellent prognosis.
PCa treatment should aim to provide each patient with the treatment that is appropriate for his personal needs, individual medical history, and tumor biology. Radical, risk prone interventions should be considered if they are unavoidable and the patient's survival gain justifies the risks associated with the intervention.
In the range of options, active surveillance is the strategy that enables risk assessment and making considered, unhurried therapeutic decisions: a retrospective controlled study with 188 participants (level of evidence 2b) showed that radical prostatectomy delayed by 26 months does not impair the chances of curative treatment in small and well differentiated tumors if they
Knowledge of the tumor biology and giving appropriate consideration to all available treatment strategies can enable primary care physicians to become important decision-makers jointly with their patients. Some food for thought: an editorial, suitably entitled "Prostate Cancer: are we over-diagnosing - or under-thinking?", concludes with the following advice: "Think more!".
TNM stages
(Source: Prostate Cancer Research Institute)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Clinically inapparent tumor not palpable or visible by imaging
T1a: Tumor incidental histologic finding in > 5% of tissue resected via TURP
T1b: Tumor incidental histologic finding > 5% of tissue resected via TURP
T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA)
T2: Tumor palpable but confined within the prostate
T2a: Tumor involves half of a lobe or less
T2b: Tumor involves more than half a lobe, but not both lobes
T2c: Tumor involves both lobes
T3: Tumor extends through the prostatic capsule
T3a: Unilateral extracapsular extension
T3b: Bilateral extracapsular extension
T3c: Tumor invades the seminal vesicle(s)
T4: Tumor is fixed or invades adjacent structures other than the seminal vesicles
T4a: Tumor invades any of bladder neck, external sphincter or rectum
T4b: Tumor invades levator muscles and/or is fixed to the pelvic wall
N Regional Lymph Nodes
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph nodes metastasis
N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension
N2: Metastasis in a single lymph node, more than 2 cm but not more than 5cm in greatest dimension; or multiple lymph node metastases, none more
than 5 cm in greatest dimension
N3: Metastasis in a lymph node more than 5 cm in greatest dimension
MX: Presence of distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
M1a: Nonregional lymph node(s)
M1b: Bone(s)
M1c: Other site(s)Conclusions
(Source: Weißbach L, Altwein J, "Active Surveillance or Active Treatment in Localized Prostate Cancer?", Dtsch Arztebl Int 2009; 106(22): 371-6, in cache)
Although randomized controlled studies are lacking, current data of active surveillance permit the conclusion that doctors have an obligation to alert patients to this option [of active surveillance]. Current guidelines on the treatment of PCa [prostate cancer] also confirm that the treatment of localized prostate cancer has undergone a rethink. However, this is barely reflected in clinical practice, at least not in Germany. In spite of the shift in tumor stage to earlier diagnosis as described earlier, the number of radical prostatectomies is rising steadily, particularly in the group of patients for whom active surveillance as laid out in the latest guidelines would be a suitable option. According to 2006 DRG statistics, almost 69% of men younger than 70 undergo RP. The numbers of operations have risen in recent years. The Brandenburg cancer registry shows that the following therapies were applied in men younger than 70 with tumor categories pT1 to pT3, for 2003 - 2005:
The use of Power Doppler Ultrasound
(Source: Ito H et al., "Visualization of prostate cancer using dynamic contrast-enhanced MRI: comparison with transrectal power Doppler ultrasound", British Journal of Radiology (2003) 76:617-624, im Cache)
Both
can be used to demonstrate hypervascularity in many prostate cancers. DCE-MRI was significantly more sensitive than PDUS for visualizing of prostate cancers without loss of specificity in the peripheral zone.