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Saleh et al. Improvement of prostate cancer detection

were 0.58, 0.55 and 0.56, respectively. Similarly, some
earlier reports found disappointing results for these
biomarkers. Although the negative findings of the
[42]
present study regarding IGF-1, IGFBP-3 or CgA serum
levels in differentiating between the PCa and control
groups; are notable, analysing the combination of these
markers with PSA either in the PCa and control groups
revealed that their combinations with serum tPSA
level, (IGF-1/tPSA, IGFBP-3/tPSA and CgA/tPSA)
were differentiated significantly among PCa, BPH
patients and healthy individuals. These combinations
could, potentially, effectively distinguish PCa patients
Figure 2: Validity (sensitivity and specificity) of parameters for
prediction of future PCa occurrence, estimated by AUC. PCa: from non-malignant individuals. Also, IGF-1/tPSA ratio
prostate cancer; AUC: area under curve; IGF-1: insulin-like growth can significantly differentiate between localized and
factor-1; IGFBP-3: IGF binding protein-3; CgA: chromogranin A; metastatic PCa. Moreover, in our study, the ratios
tPSA: total prostate specific antigen; f/tPSA: free/total prostate
specific antigen of IGF-1/tPSA and IGFBP-3/tPSA (AUC of 0.85 and
0.86, respectively) improved cancer detection, in
Table 2: Validity* of selected markers in PCa detection comparison with PSA or f/tPSA ratio, (AUC of 0.83 and
Parameter AUC 95% CI P value 0.76 respectively). Thus it would seem that circulating
IGF-1 0.58 0.51-0.66 > 0.05 IGF-1 and IGFBP-3 concentrations are unlikely to be
IGFBP-3 0.55 0.48-0.63 > 0.05 useful in differentiating patients with BPH from those
CgA 0.56 0.49-0.64 > 0.05 with PCa, but their combinations with serum PSA level
PSA 0.83 0.76-0.90 < 0.005 (IGF-1/PSA and IGFBP-3/PSA ratios) have improved
f/tPSA 0.76 0.69-0.83 < 0.005
IGF-1/tPSA 0.85 0.78-0.92 < 0.005 the validity and correlation with the progression and
IGFP-3/tPSA 0.86 0.79-0.93 < 0.005 clinical course of the disease. The strong correlation
CgA/tPSA 0.74 0.67-0.82 < 0.05 between the defective regulation of the IGF network
IGF-I/fPSA 0.55 0.48-0.63 > 0.05 and prostate carcinogenesis has been investigated
IGFBP-3/fPSA 0.57 0.49-0.64 > 0.05 previously by measurement of another member of the
*Validity (sensitivity and specificity) for prediction of PCa IGF family, IGF-2, in patients with PCa and BPH. Also
occurrence, estimated by AUC in ROC curve analysis of
prediagnostic serum concentrations of tPSA, fPSA, IGF-I, IGFBP-3, no significant association was found between PSA and
and CgA and ratios thereof, for 72 patients with PCa and 126 IGF-2 levels. However, the combination of PSA and
control subjects. PCa: prostate cancer; ROC: receiver operating
characteristics; AUC: area under curve; BPH: benign prostatic IGF-2 improved the prognosis and discrimination of
hyperplasia; IGF-1: insulin-like growth factor-1; IGFBP-3: IGF PCa and BPH. [43]
binding protein-3; CgA: chromogranin A; tPSA: total prostate
specific antigen; f/tPSA: free/total prostate specific antigen
The successful treatment of PCa depends on detection
previous studies revealed that elevated concentrations of the disease at its earliest stages. There is significant
of IGF-1 may increase the risk of some cancers, [35,36] evidence for some novel PCa biomarkers to overcome
but results with respect to PCa have been discordant the limitations of PSA; identifying these markers will
with other reports which revealed null associations allow more appropriate screening for early disease.
similar to present study. [37,38] As with the results of However, few biomarkers have been appropriately
IGF-1 and IGFBP-3, although there was no statistical validated and/or involved in clinical approach. To date,
difference between CgA levels of PCa patients and conflicting and insufficient data have indicated that there
control groups, CgA was slightly increased in patients is still no biomarker likely to attain the desirable level
with PCa than control groups. CgA is an excellent of sensitivity and specificity. Potentially, combining use
indicator of NE cells and of NED in PCa either in tissue of biomarkers may improve the diagnostic accuracy of
or serum. The detection of CgA in the blood of patients PCa which would impact treatment outcome.
with PCa indicates a NED, either of a primary tumour
or an association with metastases. Tumors with NE In conclusion, although circulating IGF-1, IGFBP-3 and
[39]
features have displayed more aggression and are CgA are unlikely to be useful in differentiating healthy
more resistant to hormone therapy. [25] individuals or patients with BPH from those with PCa,
or in identifying PCa metastasis, the combination of
Some studies have claimed that CgA is an independent IGF-1 and IGFBP-3 with PSA has improved the overall
prognostic marker for PCa, while others have sensitivity, specificity and diagnostic accuracy of PSA
[40]
conflicted with these findings. [29,41] No PCa predictive for prediction of the disease. Further prospective
values were seen for IGF-1, IGFBP-3 or CgA; AUC studies are needed concerning the correlation of
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ May 24, 2017 87