الفهرس 
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Abstract
PC is the second most common male malignancy. Its prognosis depends on the tumor stage as well as its aggressiveness; expressed histopathologically by Gleason scores. Furthermore, optimal patient management depends on the tumor stage. Thus, accurate pre-treatment staging is the cornerstone for patient management and outcome prediction in cancer prostate.
Conventional imaging modalities include CT, MRI, and bone scintigraphy were regarded as the standard, non-invasive staging tools for many years. However, they had a major disadvantage of underestimating the disease burden on the account of their low sensitivity for the detection of metastatic lymph nodes, leading to inaccurate pre-treatment staging.
68Ga PSMA PET/CT is a relatively new imaging modality combining functional and anatomical imaging with the advantage of being specific for PC cells anywhere in the body.
68Ga PSMA PET/CT has a wide spectrum of uses in prostate malignancy, some of them are comprehensively studied while others are still under investigation. The most widely accepted use currently is the accurate initial staging of cancer prostate, as it shows high sensitivity and specificity for the detection of primary and metastatic lesions.
68Ga PSMA PET/CT also has a role in detecting the exact location of the primary tumor site within the prostate, as well as the presence of extra-prostatic extension into nearby organs as SV, the presence of regional nodal metastasis, and distant metastasis whether nodal, osseous or visceral. All of which greatly affect the staging and thus, the treatment plan.
Other potential uses of 68Ga PSMA PET/CT include predicting the long-term outcome through taking part in the assessment of the prognosis, with SUVmax being a promising prognostic parameter correlating significantly with other established prognostic parameters, including the Gleason score and the PSA levels.
In our present study, we demonstrated that the intensity of tumor-related tracer uptake on 68Ga-PSMA PET/CT correlates with PSA level.
Based on our findings, we recommend that 68Ga-PSMA PET/CT for the primary staging of PC is to be preferentially performed in tumors with high PSA level. Whereas staging with 68Ga-PSMA PET/CT in tumors with low PSA values is not advisable, taking into account the significantly lower 68Ga-PSMA uptake in these tumors. Yet, caution should be applied when using this information due to another studies found that metastasis and recurrence can happen at very low PSA level and also due to the lack of histopathological validation so we recommend further large studies to validate our hypothesis.
Also we found out that there is no correlation between the intensity of tumor-related tracer uptake on 68Ga-PSMA PET/CT and Gleason grade which can be explained by that hypothesis which assume more de-differentiation and increasing tumor heterogenicity (high Gleason grade ) leading to more aggressive phenotypes and lower level of PSMA expression, yet since our high Gleason grade patients did not undergo subsequent radical prostatectomy, immunohistochemical validation of PSMA expression or assessment of potential neuroendocrine de-differentiation (as a reason for lower PSMA expression) could not be performed. So, to validate our hypothesis high-grade disease as well as its underlying biology should be further investigated in future studies
We are aware that our study may have some limitations related to the low number of patients. Our sample size is relatively low because we aimed at creating a homogeneous patient group by only including those who were initially diagnosed with no interventions. Furthermore, the histopathological data in our study was random biopsy which could have been falsely negative, since most of our study patients didn’t undergo definitive surgery, no histopathological data from radical prostatectomy specimens or lymphadenectomies were available as the gold standard. Moreover, no bone biopsies were performed.
RECOMMENDATIONS:
Undoubtedly, there is a need for further analyses to confirm these findings and to define sensitivity and specificity in subgroups so prospective trials in large patient cohorts are necessary focusing on long- term outcomes of 68Ga PSMA PET/CT imaging and make a positive impact on the clinical workup of PC patients.
We also recommend that a larger number of patients to be included in future studies to validate the results of this study and to study more relations between clinical parameters and 68Ga PSMA PET/CT findings.
Additionally, 68Ga PSMA PET/CT based imaging findings should ideally be further supported with histopathological documentation and/or follow-up imaging results in order to confirm the nature of detected lesions and to calculate its sensitivity and specificity.
As well, we recommend initiating a prospective direct comparison between conventional imaging (bone scans, CT, or whole- body MRI) and 68Ga-PSMA PET/CT imaging for metastasis staging.