Prospects in radionuclide imaging of prostate cancer

Prostate cancer is the most common malignancy in men in the Western world and represents a major health problem with substantial morbidity and mortality. Sensitivity and specificity of digital rectal examination (DRE) and evaluation of prostate specific antigen (PSA) are excellent methods for diagnosis of prostate cancer, but have limited value for staging. Imaging of prostate cancer has become increasingly important to improve staging and management of prostate cancer patients. Conventional imaging modalities, such as transrectal ultrasound and computed tomography, show limited accuracy for a reliable assessment of prostate cancer. Diagnostic value of magnetic resonance imaging has improved by dynamic contrast enhancement (DCI-MRI) and diffusion-weighted magnetic resonance imaging (DWI). Recently, substantial progress has been made in the development of functional and molecular imaging modalities, such as positron emission tomography using radiolabeled metabolic tracers, receptor-binding ligands, amino acids, peptides, or antibodies. Here, we review the value of these novel radionuclide imaging techniques in the assessment of prostate cancer.     

Update on magnetic resonance imaging, ProstaScint, and novel imaging in prostate cancer

PURPOSE OF REVIEW: Despite marked stage migration, approximately a third of patients with clinically organ-confined prostate cancer will have extracapsular extension on pathological analysis. To improve outcomes further, alternative modalities of determining extraprostatic disease must be investigated beyond the current clinical parameters of digital rectal examination, prostate-specific antigen, and Gleason score. In addition, discerning the location of tumor in patients with biochemical recurrence directly affects treatment choice. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients. RECENT FINDINGS: Magnetic resonance imaging is most useful in the initial evaluation of men with prostate cancer. Its high specificity for the diagnosis of extracapsular extension is tempered by its low sensitivity. Positron emission tomography is used to assess regional and distant metastasis in many malignancies. Investigation into the most appropriate radiotracer for prostate cancer is paramount in any future applicability. The unique role of ProstaScint has been in evaluating patients with biochemical failure and in trying to discern metastasis before definitive therapy. The addition of spectroscopic imaging and nanoparticle infusion may lead to further improvements. Therefore, in differentiating local versus distant recurrence, appropriate interventions with radiotherapy or hormonal manipulation may be instituted. SUMMARY: Magnetic resonance imaging, ProstaScint, and to some extent positron emission tomography are all relevant imaging modalities for the evaluation of patients with prostate cancer. Current technological advances in each arena are improving the accuracy of diagnosis. Despite their specific limitations, use in the proper clinical setting may provide essential information to improve management decisions and disease outcomes.     

Imaging Prostate Cancer: An Update on Positron Emission Tomography and Magnetic Resonance Imaging

Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI allows functional assessment with techniques such as diffusion-weighted MRI, MR spectroscopy, and dynamic contrast-enhanced MRI. The most common PET radiotracer, ¹⁸F-fluorodeoxyglucose, is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline (labeled with ¹⁸F or ¹¹C), ¹¹C-acetate, and ¹⁸F-fluoride have demonstrated promising results, and other new radiopharmaceuticals are currently under evaluation in preclinical and clinical studies.     

How to improve prostate biopsy detection of prostate cancer

The combination of serum prostate-specific antigen (PSA) testing and transrectal ultrasonography is a highly effective strategy to diagnose prostate cancer at an early curable stage. Even though PSA is the most useful serum biomarker to aid in prostate cancer detection, it has limited specificity: as many as 75% of men who undergo prostate biopsy because of an elevated PSA do not have prostate cancer. Additionally, sextant prostate biopsies miss prostate cancer at least 20% of the time. To reduce the number of false-negative biopsies, many have advocated obtaining 12 or more cores in a single biopsy session. Studies have shown that this practice is safe and can enhance cancer detection modestly. Although it is unlikely that prostate cancer imaging will replace prostate biopsy in the near future, many exciting new imaging technologies should eventually improve targeting of prostate needle biopsy and reduce false-negative biopsies. Some of the most exciting areas include power Doppler sonography, microbubble intravenous ultrasound contrast agents, and magnetic resonance spectroscopy. These functional imaging modalities can assess tumor blood flow and metabolic activity at a cellular level and can detect malignant changes that may not be detected by standard anatomic imaging.     

Contrast specific imaging in the detection and localization of prostate cancer

Prostate cancer (PCa) is the most common cancer in elderly men and is one of the most important causes of death from cancer in men. The diagnosis of PCa is based on a combination of digital rectal examination, PSA and transrectal ultrasound (TRUS). However, this combination does not reach the accuracy of detection and localization necessary for proper decisions on treatment methods. Therefore, biopsies are performed in all cases for which the suspicion of PCa is raised. Even with biopsies, staging and grading of PCa is far from optimal. More accurate imaging is necessary to improve the biopsy sampling, the goals being to replace systematic biopsies by a targeted approach and to improve staging and grading of PCa. Ultrasound imaging of the prostate remains the first choice of imaging to visualize the prostate, however, gray-scale ultrasound imaging has an accuracy of about 50–60% for the detection of PCa and TRUS used for local staging has an even lower accuracy. The development of PCa is associated with changes in the metabolism of tumor cells, and therefore with changes in the blood perfusion of the involved tissue. This paper focuses on contrast specific imaging techniques to visualize these changes in blood perfusion. Techniques such as color and power Doppler imaging, and contrast enhanced imaging techniques using color and power Doppler, harmonic imaging and intermittent imaging are discussed.     

Advances in sentinel node dissection in prostate cancer from a technical perspective

The most important feature of sentinel node biopsy for prostate cancer procedure is that staging can be improved. Sentinel nodes might be found outside the extended pelvic lymph node dissection template what renders the sentinel node additive of extended pelvic lymph node dissection. At the same time, staging within the template can be further refined. We reviewed the literature regarding the sentinel node biopsy procedure for prostate cancer. PubMed and Embase were searched for all English‐language publications from January 1999 to September 2014 by using the keywords as “prostate cancer” and “sentinel lymph node” plus “biopsy” “dissection” and/or “procedure.” The present review discusses step‐by‐step sentinel node biopsy for prostate cancer. Topics of discussion are: (i) preoperative sentinel node mapping (tracers and imaging); (ii) intraoperative sentinel node identification (surgical procedure and outcome); and (iii) novelties to improve sentinel node identification (pre‐ and intraoperative approaches). Conventional sentinel node mapping is carried out after the injection of a ^99mTc‐based tracer and subsequent preoperative imaging; for example, lymphoscintigraphy and single‐photon emission computed tomography/computed tomography. This approach allowed the detection of sentinel nodes outside the extended lymph node dissection template in 3.6–36% of men with intermediate‐ and high‐risk prostate cancer. Hereby, an overall false negative rate of sentinel nodes was reported between 0% and 24.4%. To further refine the intraoperative sampling procedure, novel imaging methods such as fluorescence imaging have been introduced. Prospective randomized comparison studies are required to confirm the added benefit of sentinel template directed nodal dissection. A proper and obtainable end‐point of such a study could be the number of removed positive nodes for carrying out nodal dissection with or without sentinel template directed dissection. Similarly, the clinical impact of novel imaging technologies requires further investigation.     

Update on positron emission tomography for imaging of prostate cancer

Prostate cancer is the most common non‐cutaneous malignancy among men in the Western world, and continues to be a major health problem. Imaging has recently become more important in the clinical management of prostate cancer patients, including diagnosis, staging, choice of optimal treatment strategy, treatment follow up and restaging. Positron emission tomography, a functional and molecular imaging technique, has opened a new field in clinical oncological imaging. The most common positron emission tomography radiotracer, ¹⁸F‐fluorodeoxyglucose, has been limited in imaging of prostate cancer. Recently, however, other positron emission tomography tracers, such as ¹¹C‐acetate and ¹¹C‐ or ¹⁸F‐choline, have shown promising results. In the present review article, we overview the potential and current use of positron emission tomography or positron emission tomography/computed tomography imaging employing the four most commonly used positron emission tomography radiotracers, ¹⁸F‐fluorodeoxyglucose, ¹¹C‐acetate and ¹¹C‐ or ¹⁸F‐choline, for imaging evaluation of prostate cancer.     

Usefulness of an immunochromatographical assay, PSA Rapid Test as a primary screening test for prostate cancer

Background The recent rapid increase of mass screening for prostate cancer by measuring PSA in Japan will increase the economic burden to the healthcare system. PSA Rapid Test (PRT) is a simple inexpensive test. The usefulness of PRT as a primary screening test for prostate cancer was evaluated. Methods When we conducted educational lectures for prostate cancer in our city, screening for prostate cancer using PRT was offered to the male participants. The results of the tests were handed to participants in writing at the end of the lectures. When the results were judged as positive, letters of referral to our institute were enclosed. Results One hundred and fourteen (18.6%) of 614 men were judged as positive by PRT. Of the 114 men with positive PRT, 73 (64%) visited our institution. Finally, 37 men underwent a transrectal prostate biopsy and a diagnosis of prostate cancer was made in 21 men (3.4% of all participants). The total costs for the PSA tests in this study were summed to be approximately $2,300, while they would be approximately $9,200 if all participants had undergone screening using the conventional quantitative method from the outset. Conclusion PRT is a low-cost method to detect patients with prostate cancer. We believe the PRT is useful as an initial screening test for detecting prostate cancer and that the combination of the PRT and more precise quantitative testing would be a reasonable way to reduce the cost and achieve high detection rate.     

The role of prostate-specific antigen velocity in prostate cancer early detection

Prostate-specific antigen velocity (PSAV) is the rate of change in prostate-specific antigen (PSA) values with repeated measurement over time. Accurate use of PSAV for prostate cancer early detection requires the use of two or more PSA levels collected over approximately 1.5 to 2 years. When these specimen collection criteria are met, more than 95% of men without prostate cancer will have a PSAV less than 0.75 ng/mL/y, whereas approximately 70% of men with prostate cancer will have a PSAV above this threshold. PSAV is thus more specific than routine PSA testing for the presence of prostate cancer, because few men (< 5%) without prostate cancer have a PSAV sufficient to trigger prostate biopsy. The use of PSAV in the increasing number of men with lengthy PSA histories obtained in systematic efforts at prostate cancer early detection may aid in diagnosing prostate cancer and spare some men unnecessary prostate biopsy. This review briefly summarizes the theoretic basis and clinical utility of PSAV in prostate cancer early detection.     

Bildgebende Diagnostik des fortgeschrittenen Prostatakarzinoms

The diagnostic approach to prostate cancer is still a big challenge for the treating physician. Regarding an individualized and risk-adapted evaluation of different therapeutic options, precise diagnostic tools are crucial to accurately distinguish between localized and advanced prostate cancer. Imaging of advanced prostate cancer is currently changing due to numerous technical innovations. While choline-based hybrid positron emission tomography-computed tomography (PET/CT) has been established as an important diagnostic tool in clinical imaging of advanced prostate cancer, well-investigated methods, such as magnetic resonance imaging (MRI) and bone scintigraphy are currently expanding the diagnostic potential due to technical improvements. The specific use of imaging for advanced prostate cancer may help to offer the patient a well-tailored oncologic therapy. Further research is needed to evaluate whether this individualized therapy can consistently improve the prognosis of patients suffering from advanced prostate cancer.     

The positive yield of imaging studies in the evaluation of men with newly diagnosed prostate cancer: a population based analysis

PURPOSE: We determine the positive yield of imaging studies performed on men with newly diagnosed prostate cancer. MATERIALS AND METHODS: A prospective, population based survey was conducted on 3,690 men with prostate cancer diagnosed between October 1, 1994 and October 31, 1995. Cases were identified by the rapid case ascertainment systems used in 6 geographic regions participating in the Surveillance, Epidemiology and End Results Program. Based on information captured in primary medical record reviews we estimated the positive yield of bone scans, computerized tomography (CT) and magnetic resonance imaging. RESULTS: The positive yield of bone scan and CT was less than 5% and 12%, respectively, for all men with prostate specific antigen (PSA) 4 to 20 ng./ml., and less than 2% and 9%, respectively, for those who also had a Gleason score of 6 or less. Only men with PSA greater than 50 ng./ml. and those with Gleason scores 8 to 10 and PSA greater than 20 ng./ml. had positive yields greater than 10% and 20% for bone scan and CT, respectively. CONCLUSIONS: Imaging studies designed to identify metastases and/or extracapsular extension in men with newly diagnosed prostate cancer frequently have a low positive yield. Wide variations exist in the use of imaging studies and are associated with tumor factors, such as Gleason score and serum PSA, and nontumor factors, such as state of residence. More extensive cost-effectiveness analyses are needed to define appropriate guidelines for ordering imaging studies to optimize the positive yield among men with newly diagnosed prostate cancer.     

Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

The reported incidence of prostate cancer has risen since the implementation of screening. It is felt that the introduction of widespread prostate-specific antigen testing is responsible for most patients with prostate cancer now being diagnosed with asymptomatic, clinically localised disease. Diagnosis at this stage is associated with significantly improved treatment outcomes and longer life expectancy. Although there is evidence that screening has reduced prostate cancer mortality, there is a risk of over-diagnosis and over-treatment of early state prostate cancers, including clinically insignificant and indolent cancers. Active surveillance and focal therapy have been advocated as potential management options for some patients. However, these approaches face several challenges. Biopsy sampling errors together with less than optimal imaging of tumours can lead to difficulties in selecting suitable low-risk patients for these options. To overcome these challenges, novel approaches to the staging and monitoring of patients with early prostate cancer are being developed. These include new imaging techniques, such as multi-parametric magnetic resonance imaging, and the development of new biomarkers and biopsy-based methods. These techniques aim to assess the potential of a specific tumour to be aggressive, and to improve patient outcomes. The aim of the present paper is to summarise presentations and debates at the third annual Interactive Genitourinary Cancer Conference concerning the use of population-based screening methods and the roles of active surveillance and focal therapy as prostate cancer treatments. The application of novel imaging biopsy-based methods and biomarkers in early-stage prostate cancer will also be explored.     

Thermal therapy of prostate cancer using magnetic nanoparticles

A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer.     

A population-based study of renal cell carcinoma and prostate cancer in the same patients

OBJECTIVE: To investigate the incidence of prostate cancer in men with renal cell carcinoma (RCC) and the incidence of RCC in men with prostate cancer. METHODS: We evaluated the database of the Surveillance, Epidemiology and End Results Program of the National Cancer Institute from 1973 to 1996, to calculate the incidence of RCC in men with prostate cancer and the incidence of prostate cancer in men with RCC. The standardized incidence ratio (SIR, observed/expected) was calculated for each of the scenarios of interest, as well as for RCC and prostate cancer in men with other common malignancies. Lung/bronchus cancer, colon/rectal cancer, and non-Hodgkin lymphoma were selected for the control scenarios because they are the most common non-urological cancers among men in the USA. RESULTS: There was a higher incidence of RCC in men with prostate cancer (SIR 1.25, P < 0.01). RCC incidence was also higher in men with each of the other malignancies. Prostate cancer incidence was higher in men with RCC (SIR 1.42, P < 0.001), but was not significantly elevated for any of the control scenarios. CONCLUSIONS: The incidence of RCC is higher in men with each of the index cancers, whereas that for prostate cancer was higher only in men with RCC. A common aetiological factor is possible. However, it is also possible that detection bias explains these findings. Serial imaging might increase the detection of RCC among patients with a variety of index malignancies. Patients with RCC who are followed by a urologist might be screened more rigorously for prostate cancer than patients with other primary malignancies, leading to increased detection in these men.     

Development of prostate cancer treatment: the good news

Prostate cancer is the most commonly diagnosed cancer in American men representing one-third of all new cancer cases each year. This translates into one out of every six American men being diagnosed with prostate cancer over the course of their lifetimes. Over 31,000 of these men die each year from prostate cancer. Before the 1980's, 50% of men were diagnosed with widespread metastatic disease and there were few therapeutic choices for patients. The good news for patients is that, over the last 30 years there have been significant advances in detection and prognostication as well as major improvements in the surgical, radiation, and medical oncological management of prostate cancer. This review describes the evolution of these therapeutic modalities for prostate cancer. This evolution has been driven by the explosion of knowledge concerning cancer in general and in the specific biology of prostate cancer in particular over the last 30 years. This knowledge has been obtained by concentrating human and financial resources in organ specific studies of the prostate. The end result of this effort is that, today, 85% of new prostate cancer cases are diagnosed at local and regional stages and the 5-year relative prostate cancer survival rate has increased by 20% since 1985. In addition, the therapeutic approach to prostate cancer can now be individualized based on the characteristics of the patient's disease. Finally, recent data suggest that the death rate from prostate cancer is decreasing by approximately 4% per year since 1994. Further good news for patients is that new discoveries about the biology of prostate cancer are rapidly being translated into new therapies, a large number of which are currently being tested in clinical trials. Continued allocation of appropriate human and material resources should yield new, more effective therapies for prostate cancer that will further impact patient quality of life and survival in the 21st century.     

Salvage-Prostatektomie

Organ-confined prostate cancer can be treated with curative intent by different types of radiotherapy or by radical surgery. Regardless of improvements in radiotherapy about 60% of patients with prostate cancer develop biochemical recurrence (BCR) which is defined by the progressive increase in serum prostate-specific antigen (PSA) and necessitates further diagnostic procedures. If non-organ-confined cancer and metastasis are categorically excluded by cross-sectional imaging using computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography CT (PET-CT) and bone scintigraphy, a prostate biopsy should be performed. Biopsy proven detection of recurrent or persisting prostate cancer after irradiation is essential prior to a salvage prostatectomy. The function of the lower urinary tract should be evaluated prior to surgery. Preoperative PSA measurement is the best prognostic indicator prior to surgery. Salvage prostatectomy in irradiated patients is more challenging and requires extensive skill. The most common complications are incontinence, rectal injury and anastomotic strictures. Both functional and oncologic outcome have improved due to better irradiation techniques and surgical skills. Provided post-radiotherapy recurrence of prostate cancer is diagnosed early enough, curing is possible by salvage prostatectomy.     

Salvage prostatectomy. Principles of diagnostics and operative therapy

Organ-confined prostate cancer can be treated with curative intent by different types of radiotherapy or by radical surgery. Regardless of improvements in radiotherapy about 60% of patients with prostate cancer develop biochemical recurrence (BCR) which is defined by the progressive increase in serum prostate-specific antigen (PSA) and necessitates further diagnostic procedures. If non-organ-confined cancer and metastasis are categorically excluded by cross-sectional imaging using computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography CT (PET-CT) and bone scintigraphy, a prostate biopsy should be performed. Biopsy proven detection of recurrent or persisting prostate cancer after irradiation is essential prior to a salvage prostatectomy. The function of the lower urinary tract should be evaluated prior to surgery. Preoperative PSA measurement is the best prognostic indicator prior to surgery. Salvage prostatectomy in irradiated patients is more challenging and requires extensive skill. The most common complications are incontinence, rectal injury and anastomotic strictures. Both functional and oncologic outcome have improved due to better irradiation techniques and surgical skills. Provided post-radiotherapy recurrence of prostate cancer is diagnosed early enough, curing is possible by salvage prostatectomy.     

Prostate-specific antigen doubling time as a prognostic marker in prostate cancer

Prostate cancer has a varied natural history. Men with similar serum prostate-specific antigen (PSA) levels, clinical stages, and histologic features in their tissue specimens can have markedly different outcomes. While prostate cancer is lethal in some patients, most men die with cancer rather than because of it. Moreover, histologically apparent cancer can be found in the prostate glands of approximately 42% of men over 50 years of age who die from other causes, but the lifetime risk that a man in the US will be diagnosed with prostate cancer is estimated to be 11% and the risk of dying from the disease is only 3.1%. Consequently, appropriate disease management requires risk assessment. How likely is it that a given man's cancer will progress or metastasize over his remaining lifetime? What is the probability of successful treatment? What are the risks of adverse effects and complications of each treatment? Physicians use a variety of clinical and pathologic parameters to assess the risk that a given cancer poses to an individual patient. In addition to the accepted parameters of serum PSA level, clinical staging, and pathologic grading and staging, PSA doubling time has emerged as an important factor in the evaluation of men with newly diagnosed prostate cancer or prostate cancer that recurs after treatment. PSA doubling time can also be used as a surrogate marker for prostate cancer-specific death. This review summarizes current knowledge regarding the role of PSA doubling time as a prognostic marker in men with prostate cancer.     

Molecular profiling of indolent human prostate cancer: tackling technical challenges to achieve high-fidelity genome-wide data

The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.     

New imaging techniques in prostate cancer

Correct staging of prostate cancer at initial diagnosis, as well as accurate staging and tumor localization with biochemical recurrence, remains generally inaccurate with current imaging techniques. Newer modalities are being investigated to accurately identify patients with prostate cancer at different stages of disease. Identification of locally recurrent disease or distant metastasis at the time of biochemical failure after local therapy will help guide treatment options and avoid potentially toxic salvage therapies in patients who will not benefit. A review of prostate cancer imaging literature over the past 12 months was performed to identify emerging imaging modalities that may be beneficial in the management of prostate cancer. Enhanced transrectal ultrasonography modalities, including ultrasound contrast agents, color and power Doppler, and elastrography, have demonstrated incremental benefit when combined with standard grayscale ultrasonography to accurately target and diagnose prostate cancer. Endorectal MRI, with contrast enhancement and spectroscopic imaging, shows promise in the initial staging of prostate cancer prior to local therapy. The use of positron-emission tomography scan for prostate cancer remains to be defined, but may help delineate the site of recurrence with biochemical failure after local therapy. Several new imaging modalities show promise for the evaluation of the patient with prostate cancer. Enhanced ultrasonography techniques may prove to be more accurate in diagnosing prostate cancer over standard gray-scale ultrasonography. Accumulating evidence supports the use of endorectal MRI and spectroscopy to help treatment planning with either surgical or radiotherapeutic approaches. Although intriguing, the available data for positron-emission tomography in prostate cancer remains too shallow to advocate routine use.