Imaging Techniques: the Screening and Diagnosis of Prostate Cancer - Essay Example

?Imaging techniques that can be used for the screening and diagnosis of pro cancer Introduction Pro cancer results in large number of deaths among the US men, even though the disease itself cannot be termed as lethal (Jemal, Siegel, Ward, et al., 2008). It may range from asymptomatic to fast progressing systemic malignancy. It is often considered as a normal age-related occurrence, owing to its high prevalence. Screening for prostate cancer by prostate-specific antigen and digital rectal examination has moved the diagnosis of this disease to an organ confined, lower grade disease. Now the main challenge lies in characterising clinically admissible tumours from the ones that would have remained undiagnosed if the patient were unscreened. The current development of various imaging techniques and integration of molecular, functional anatomic data make way for better diagnosis and classification of prostate cancer. However, the appropriate use of imaging is difficult to define, as many controversial studies regarding each of the modalities and their utilities can be found in the literature. However, uses of imaging in medical practices have progressed slowly owing to the absence of a precise definition for its appropriate use. The current method adopted for diagnosing and managing prostate cancer follows the use of various pathologic risk factors such as clinical stage and Gleason score, and serum prostate-specific antigen (PSA). The imaging techniques traditionally used for diagnosing prostate cancer can no longer be counted as reliable enough to locate the minute quantities of prostate cancer often seen at the presentation stage, as applicability of PSA serum has undergone large-scale stage migration. Current observations reveal that PSA tests provide very little data on the exact location and the extent of disease. Test limitations in this regard include failure to detect extraprostatic disease when PSA levels are low, lack of correlation with cancer volume mainly due to large contributions made by the benign part of the gland, and low specificity while detecting cancer. The advanced form of imaging techniques (molecular based) have primarily focused on elaborating the specificity and sensitivity of cancer diagnosis through knowledge of the particular characteristics of disease biology. Thus, evolution of modern imaging modalities has created a new scope for improved clinical diagnosis and management of prostate cancer. Technological advances in the process of imaging have allowed for the use of disease biology, which helps in a more accurate capture of the location, extent of spread, and aggressiveness of the disease. This article, studies the various imaging techniques that can be used for the screening and diagnosis of prostate cancer. Discussion Brief background on named cancer including prevalence and current therapies The prostate is a small walnut shaped gland located in the pelvis region (between the bladder and the penis) and is found only in men. It covers the urethra, a tube that carries the urine from bladder to penis (NHS, 2012). Its main function is to take part in semen production. The prostate gland produces a concentrated white fluid, which is then diluted by the addition of a protein, referred to as prostate-specific antigen or PSA. The testicles, which produce sperm, then mix with the fluid, to form semen. As men get older, the prostate gland tends to get bigger. While this may lead to no clinical issues for a majority of the men, some may develop symptoms, when the gland becomes bigger and starts pressing on the urethra, causing urinary problems. This medical condition is known as benign prostatic hyperplasia or BPH, and it mainly affects men over 50 years of age. However, it is not carcinogenic in nature and is treatable. Prostate cancer is one of the common forms of cancer seen amongst the UK men. Annually, around 36,000 men develop prostate cancer in the UK and account for nearly 25% of all the cancer cases reported in men (NHS, 2012). Reports show that, “In 2009, 40,841 men in the UK were diagnosed with prostate cancer. In 2010, there were 10,721 deaths from prostate cancer in the UK. In 2005-2009, 81% of men in England survived their prostate cancer for five years or more” (Cancer Research UK, 2012). Prostate cancer is mostly seen in men above 70 years of age, as the chances of developing the disease increases with age. Observations also reveal that prostate cancer is more commonly found within African and African-Caribbean men and are less common amongst in Asian men (NHS, 2012). The causes for this disease remain unknown, and prostate cancer becomes incurable if diagnosis occurs late. Therefore, for a successful treatment of the illness it is imperative that the disease is diagnosed early; hence, the current focus on developing advanced imaging techniques for a better and early detection of the disease. Current techniques under use for prostate cancer screening and diagnosis Currently three diagnostic tests for prostate cancer are in practise. These are, Transrectal ultrasound or TRUS biopsy, Prostate Specific Antigen or PSA, and measurement Digital Rectal Examination or DRE, but all these techniques have their own disadvantages (Chamberlain, Melia, Moss and Brown, 1997). Of these three, the PSA test is widely accepted but there are many disadvantages associated with this technique. An enzyme that is produced by the prostate, PSA can be measured in a patient’s blood. Besides the presence or absence of carcinogenic factor, various other factors also affect the PSA levels, such as obesity, age, and benign prostatic hypertrophy (Banez, et al., 2007). Currently, rates of over-detection in PSA tests range from 27% to 56% (Dall'Era, Cooperberg, Chan, et al., 2008). PSA is mainly specific for prostate but lacks any specificity for prostate cancer, and any procedure that disturbs normal functioning of the prostate allows diffusion of PSA into microvasculature and stroma. While PSA level serum links positively with presence of seminal vesicle invasion tumour and capsular perforation, volume, histologic grade, and clinical stage, it has no value while predicting the stage for individual cases (Bostwick, 1994). Despite its various disadvantages, PSA remains the only biomarker that is still widely used for detecting prostate cancer. However, currently researches are going on that aim at making the PSA test more precise and takes into consideration PSA density (volume/size of prostate gland), velocity (how rapidly the levels increase with time), and the ratio between complexed and free PSA (Burford, Kirby and Austoker, 2008).  Complexed PSA is typically associated with cancer while free PSA is linked with benign prostatic hyperplasia, so it is possible to arrive at a conclusive decision from a study of their ratios (which may help to read the total PSA levels), when combined with the prostate size, previous biopsy reports, co-morbidities, DRE findings, and ethnicity of the patient (Burford, Kirby and Austoker, 2008). Current imaging techniques that are widely used, such as, nuclear medicine, CT, MRI, ultrasound, fail to diagnose the diseases at an early stage, while providing very little data on disease staging (Albrecht, Buchegger, Soloviev, et al., 2007). The use of ultrasound for cancer detection has shown low specificity with low negative values for predicting the disease. Within the current medical care, transrectal ultrasound (TRUS) is widely used for guiding biopsy reports instead of identifying the extent and exact location of prostate cancer. However, newer and more promising techniques (alone or in combination with the standard imaging techniques) are currently under scientific investigation. The primary goal for an improved imaging technique that could be used for prostate cancer diagnoses for deriving better results would be a greater ability to characterise the disease accurately through a synthesis of functional, molecular, and anatomical imaging data. Until date, there have been no consensus as regards the use of imaging modalities for screening and diagnosing primary prostate cancers, despite being acknowledged that selection of an imaging modality must be based on questions and answers that address the requirements of each individual patient. The current imaging techniques in use and other techniques that are under consideration 1. Transrectal ultrasound Contrast-Enhanced Ultrasound: in order to increase the ultrasound sensitivity there has been technological developments, where multiple additional techniques have been created based on the ultrasound. Contrast enhanced TRUS blends the traditional ultrasound values in temporal and spatial visualization of prostate gland with observations that prostatic tumour growth actuates neovascularization (Van Moorselaar and Voest, 2002). In Contrast enhanced TRUS method, the intraprostatic vascular structures are measured using micro bubbles (contrast agent), where 1–10?m micro bubbles are injected into a patient’s bloodstream and the bubbles are then studied as they move inside the prostate gland by transrectal ultrasound probe. Abnormal visualisations on CEUS correspond to prostate cancer in pathology reports (Strohmeyer, Frauscher, Klauser, et al., 2001). Grey-Scale Ultrasound: Grey-scale transrectal ultrasound is the most common technique used for diagnosing prostate cancer, especially while directing needle biopsies. In cases where prostate cancer is being suspected owing to high levels of PSA or abnormal DRE report, generally the next step taken is the systematic needle biopsy, where TRUS is plays and effective and important role in identifying prostate outlines in transverse and sagittal planes. This technique is available easily and is a simple process, and gives more or less a correct estimation of prostate volume as essential factor in determining the density of PSA density (Terris and Stamey, 1991). Prostate cancers are viewed as hypoechoic lesions on TRUS such lesions are likely to contain carcinogenic cells within the isoechoic areas (Ellis, Chetner, Preston, and Brawer, 1994). However, majority of the hypoechoic lesions detected by TRUS turn out to be non-carcinogenic, and while nearly 30% of all prostate cancers show isoechoic cells only around 1% of them have hyperechoic (Shinohara, Wheeler, and Scardino, 1989). While the positive predictive value of grey-scale ultrasound is around 53%, the negative predictive value is nearly 72%. Thus, the use of Grey-scale transrectal ultrasound in screening and diagnosing prostate cancer has limitations. Using contrast enhanced-ultrasound for targeting biopsies have resulted in detecting more cancers (having less cores) when compared to the grey-scale ultrasound biopsies (Mitterberger, Horninger, Pelzer, et al., 2007). The same research also detected nearly 2.5 times more chances of precise prostate cancer detection using contrast-enhanced ultrasound. Summarily the study showed that nearly 51% - 63% of all prostate cancers were diagnosed through the use contrast-enhanced ultrasound. 2. MRI There have been extensive researches on MRI on its ability to diagnose prostate cancers. Endorectal coil MRI provides a scope for improved visualization of prostate anatomy and location tumour and extent of the disease within the gland. Images of the patient are taken using a whole body scanner with endorectal coil and a pelvic phased array coil, where a magnetic coil is placed inside the rectum. Here both T1 and T2 weighted visuals are taken, however, cancer visualization is made, in most cases, on T2 weighted images, where the dark points indicate carcinogenic cells. There has been limited analysis on the use of MRI on cancer patients by itself. In individuals not marked as cancer patients, MRI has shown to produce poor specificity and low sensitivity (Coakley, Qayyum, and Kurhanewicz, 2003). Similar to ultrasound, adding endorectal MRI to systematic biopsy is unlikely to improve prostate cancer diagnosis. In patients having older reports showing negative biopsies and current high levels of PSA, the endorectal MRI is likely to show a better ability to categorise prostate cancer risk (Beyersdorff, Taupitz, Winkelmann, et al., 2002). In retrospective pathological evaluation, matching histologic tumour location to endorectal MRI has produced poor results. 3. Lymphotropic magnetic nanoparticle infusion prior to MRI (Combidex) The main disadvantage of cross-sectional imaging modalities used for identifying lymph node cancer is its failure to locate the disease in small lymph nodes (5-10 mm). Owing to this, various researchers have tried finding molecular means of differentiating normal lymphatic tissues from the cancerous ones. In one such method, a dilution of supermagnetic nanoparticles is pushed into the lymph tissue via the interstitial lymphatic fluid transport system Combidex is a detecting agent (ferumoxtran-10) made of nanoparticles of the iron oxide compound, which if added before MRI, allow differentiation between lymphoid tissues and cancer cells within lymph nodes. Since this technique has the potential to distinguish cancerous cells even in lymph nodes (less than 10 mm in size), FDA is currently reviewing Combidex. 4. The ProstaScint (Cytogen Corp., Princeton, NJ) This process uses radiolabeled monoclonal antibodies to prostate-specific membrane antigens or PSMA, for locating prostate cancer cells, and FDA approves its use for prostate cancer patient scanning. Patients are given intravenous infusion containing five mCi of radiolabeled antibodies, after which cross-sectional and planar single photon emission computerized tomography or SPECT, is made. The findings of the imaging are often subtle, and there is a risk factor of producing false positive image, owing to blood vessels or bowel overlying the lymph nodes, however if the reader is experienced these errors can be avoided. The scan is a valuable technique for diagnosing and staging prostate cancer, especially in cases of newly detected prostate cancer, and allows for appropriate selection of individuals from high-risk segment for various curative therapies. PET is another imaging technique under consideration for some time, but there have been limited researches on this process for diagnoses of patients having occult metastases with recurrent prostate cancer. Its use appears to have certain disadvantages with conventional tracing agents as 18F fluorodeoxyglucose, and newer agents such as 11C-choline offer better promises for effective imaging results in cases of prostate cancer (Zheng, Gardner, Raikwar, et al., 2004). Various reviews have shown that MRI, PET and Transrectal ultrasound are cost-effective in the diagnosis and management of patients with prostate cancer (Miles, 2002). The cost-effectiveness of these newly developed imaging techniques is more applicable as regards staging, monitoring and diagnosis, instead of screening. However, owing to a gap in transferring transnational research results between tumours translates into the fact that further studies are required for getting a better idea of the global nature of cost-effectiveness of these techniques. With health care resources, being increasingly made on cost-effectiveness of a process, it is necessary for cancer specialists to find procedures that link evidence-based medicine with imaging. Since many of the currently developed imaging techniques used for assessing therapeutic treatment are not applicable for diagnoses, it is necessary to delineate and develop analytical procedures more appropriate for prostate cancer imaging (Miles, 2002). Conclusion While imaging techniques for diagnosing prostate cancer have made great advances in the recent years, there are still difficulties associated with distinguishing the cancer cells in small volumes within the prostate gland and metastatic sites. Use of molecular imaging modalities such as MRI, ProstaScint, Combidex, ProstaScint, and PET provides opportunities to have a better understanding of the various stages in the development of prostate cancer within a human body and a grasp of its biology. The patients must be carefully selected for producing correct imaging results is essential and the results are often dependant on the correct use of knowledge of the limitations and capability of each study. In staging, monitoring and diagnosis of prostate cancer, applicability of an imaging technique relies on prevalence of the aspired result. Careful analysis of risk factors, adequate training of people employed in the radiology department, will help in the proper use of new imaging techniques. Further clinical researches and advancement in technology would undoubtedly help to increase the use of imaging modalities in all areas of prostate cancer care. References Albrecht S, Buchegger F, Soloviev D, et al., 2007. 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