Imaging in prostate cancer

Prostate cancer is the most common malignancy in men, in general. Most patients diagnosed with prostate cancer have localized disease confined to the prostate. A small percentage of patients with aggressive tumors will progress to develop local, extracapsular tumor extension and distant metastases. The aim of prostate cancer management is to identify and treat those patients with aggressive disease before they develop locally advanced or metastatic disease, and to avoid overtreating indolent tumors, which are unlikely to be life threatening. Imaging has been shown to be valuable in local staging of prostate cancer and as an aid to the management of clinically significant disease. In this article, we discuss the different established imaging modalities and emerging techniques for prostate cancer imaging in patients with clinically localized disease who may be suitable for radical treatment.     

Imaging of prostate cancer

PURPOSE OF REVIEW: Appropriate imaging of prostate cancer is a crucial component of staging and therapy application. The purpose of this review is to highlight the most important developments in novel imaging modalities reported in the past year. RECENT FINDINGS: Transrectal ultrasound is used to guide needle biopsy and brachytherapy. Improved results are obtained with color and power Doppler transrectal ultrasound with sonographic contrast agents. The role of elastography in prostate cancer remains to be elucidated. Magnetic resonance imaging is now widely used for staging before treatment and accumulating data indicate the utility of this technique with magnetic resonance spectroscopy in staging and follow-up. Positron-emission tomography alone or especially in combination with computed tomography imaging with the new radiotracers (11)C-choline, (18)F-fluorocholine, (11)C-acetate and (18)F-fluoride have shown promising results. Further investigations in larger clinical studies are necessary to establish the role of these imaging techniques in the management of patients with prostate cancer. SUMMARY: This report provides a summary of novel types of imaging and indicates their promise in prostate cancer.     

Imaging for prostate cancer

The increased incidence and awareness of prostate cancer, together with developments in treatment, has generated a significant need for appropriate imaging to detect and stage the tumour initially, guide radiotherapy delivery and monitor disease on follow-up. Transrectal ultrasound is usually the first imaging investigation, and its role is primarily to guide prostate needle biopsy. It also has an established role in imaging-guided treatments, such as brachytherapy. Magnetic resonance imaging has developed considerably in recent years, and is now the principal staging investigation before treatment. Innovations in functional and biological imaging of the prostate will, in the future, contribute valuable information to support parallel developments in radiotherapy techniques for prostate cancer. The ultimate goal is a coordinated diagnostic and therapeutic approach to individualise and optimise the treatment plan for patients with prostate cancer.     

Imaging modalities for prostate cancer

Prostate cancer is the most frequently diagnosed malignancy in the Western male population and the associated socioeconomic impact on healthcare is of great concern. Since the early 1990s, MRI has evolved into an important diagnostic imaging modality for prostate cancer patients. In this review, the applications of diagnostic imaging modalities in prostate cancer, such as transrectal ultrasound, computed tomography and MRI are described. The clinical value of these techniques in prostate cancer detection, localization, characterization, staging and active surveillance are discussed.     

Imaging and cancer: A review

Multiple biomedical imaging techniques are used in all phases of cancer management. Imaging forms an essential part of cancer clinical protocols and is able to furnish morphological, structural, metabolic and functional information. Integration with other diagnostic tools such as in vitro tissue and fluids analysis assists in clinical decision‐making. Hybrid imaging techniques are able to supply complementary information for improved staging and therapy planning. Image guided and targeted minimally invasive therapy has the promise to improve outcome and reduce collateral effects. Early detection of cancer through screening based on imaging is probably the major contributor to a reduction in mortality for certain cancers. Targeted imaging of receptors, gene therapy expression and cancer stem cells are research activities that will translate into clinical use in the next decade. Technological developments will increase imaging speed to match that of physiological processes. Targeted imaging and therapeutic agents will be developed in tandem through close collaboration between academia and biotechnology, information technology and pharmaceutical industries.     

Imaging prostate cancer: current and future applications

Various treatment options are available for adenocarcinoma of the prostate--the most common malignant neoplasm among men in the United States. To select an optimum management strategy, we must be able to identify an organ-confined disease (in which local therapy such as surgery or radiation may be beneficial) vs prostate cancer beyond the confines of the gland (for which other treatment approaches may be more appropriate). At present, no standard imaging modality can by itself reliably diagnose and/or stage adenocarcinoma of the prostate. Standard transrectal ultrasound, magnetic resonance imaging (MRI), computed tomography, bone scans, and plain x-ray are not sufficiently reliable when used alone. Fortunately, advances in imaging technology have led to the development of several promising modalities. These modalities include color and power Doppler ultrasonography, ultrasound contrast agents, intermittent and harmonic ultrasound imaging, MR contrast imaging, MRI with fat suppression, MRI spectroscopy, three-dimensional MRI spectroscopy, elastography, and radioimmunoscintigraphy. These newer imaging techniques appear to improve the yield of prostate cancer detection and staging, but are limited in availability and thus require further validation. This article reviews the status of current imaging modalities for prostate cancer and identifies emerging imaging technologies that may improve the diagnosis and staging of this disease.     

Imaging of distant metastases of prostate cancer

The detection of distant metastases at the initial diagnosis of prostate cancer (PCa) establishes the treatment approach and has a prognostic value, nevertheless it is not well established. Since proposed staging approaches often contradict each other, we aimed to compare the current imaging techniques for staging of advanced PCa, including future applications of the most innovative methods. Conventional imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have been employed for metastatic staging (both N and M staging) of men with high-risk PCa, but surgical pelvic dissection remains the gold standard for N staging. However, functional MRI by using diffusion-weighted imaging, MR lymphography (MRL) with ultra-small paramagnetic iron oxide particles (USPIO), and hybrid PET/MRI imaging showed both high sensitivity and high specificity for nodal staging and depicting metastases. The standard of practice for M staging in PCa includes the radionuclide bone scan and targeted X-ray film, but their performance has generally been poor. Recently, MRI showed promising results with applications in both local and distant staging. Finally, with the development of new PET tracers, PET/CT and PET/MRI offer a combination of excellent pharmacokinetic characteristics, functional information, and precise anatomic localization and morphological correlation of tumor lesions.     

Hypofractionation for prostate cancer: a critical review

In ideal circumstances, the fractionation schedule of radiotherapy should match the fractionation sensitivity of the tumor relative to the nearby normal tissues. A number of recent publications have suggested that the alpha-beta ratio (alpha/beta) for prostate is low, in the range of 1 to 3 Gy. If alpha/beta is truly low, then hypofractionated schedules using fewer, larger fractions should improve the therapeutic ratio. This critical review examines the clinical experience with hypofractionation. Several prospective trials indicate that toxicity is limited with sophisticated dose delivery and compact clinical target volume to planning target volume margins, but the single-arm nature of these trials precludes definitive statements on efficacy. Several large randomized trials comparing conventional fractionation to hypofractionation are ongoing and are described. Until these trials are completed and the results submitted for rigorous peer review, the notion that alpha/beta for prostate cancer is low remains an unconfirmed hypothesis.     

Genetic susceptibility to prostate cancer: a review

A genetic component in prostate cancer has been recognized since decades. Through numerous epidemiological and molecular biological studies, much evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PCa) susceptibility. Since the mapping of a high-penetrant PCa susceptibility locus at 1q24–25, much attention has been paid to the identification of PCa susceptibility genes. So far, seven loci have been mapped, and at three of these loci, genes have been cloned and mutations identified. Yet their role in hereditary and sporadic disease is still under debate and probably very modest. Although research on hereditary prostate cancer has improved our knowledge of the genetic etiology of the disease, still a lot of questions remain unanswered. Here, we aim to review the genetic epidemiological and molecular biological research in the field of hereditary prostate cancer and the problems that are encountered with this research.     

Second-line chemotherapy in metastatic docetaxel-resistant prostate cancer: a review

The results of cytotoxic therapy in the second-line setting of metastatic castration-resistant prostate cancer have demonstrated that disease is poorly controlled after taxane resistance with a time to progression of 3 months or less. Many trials of second-line chemotherapy have been disappointing. However, most of patients with docetaxel-pretreated castration-resistant disease receive a second-line chemotherapy. Molecular mechanism of castration resistance and docetaxel resistance is resumed, and clinical trials of second-line chemotherapy after docetaxel progression are reviewed. Reintroduction of docetaxel after a drug-free interval is an active treatment in docetaxel-pretreated patients, and only recently a prospective study documented a survival benefit of 2.4 months after second-line taxane-based chemotherapy of metastatic docetaxel-resistant prostate cancer. Although a second-line chemotherapy with a taxane could improve overall survival, a change of biology of castration-resistant prostate cancer after docetaxel is suggested, as inferred by the renewed hormonal sensitivity, whose role on survival remains unknown, and from the activity of antiangiogenic drugs.     

Screening for prostate cancer: A Cochrane systematic review

Objectives The objective of this systematic review was to determine whether screening for prostate cancer reduces prostate cancer mortality. Methods A systematic search for randomised controlled trials was conducted through electronic scientific databases and a specialist register of the Cochrane Prostatic Diseases and Urologic Cancers Group. Manual searching of specific journals was also conducted. Two authors independently reviewed studies that met the inclusion criteria. Studies were independently assessed for quality. Data from included studies was also extracted independently. Results Two randomised controlled trials were included however, both trials had methodological weaknesses. Re-analysis of the reported data using intention-to-screen and meta-analysis indicated no statistically significant difference in prostate cancer mortality between men randomized for prostate cancer screening and controls (RR 1.01, 95% CI: 0.80–1.29). Conclusions Given that only two randomised controlled trials were included, and the high risk of bias of both trials, there is insufficient evidence to either support or refute the routine use of screening compared to no screening for reducing prostate cancer mortality. Currently, no robust evidence from randomised controlled trials is available regarding the impact of screening on quality of life, harms of screening, or its economic value. Results from two ongoing large scale multi-center randomised controlled trials, which will be available in the upcoming few years, will assist patients and health professionals in making an evidence-based decision regarding the effectiveness of screening for prostate cancer This paper is based on a Cochrane review first published in The Cochrane Library 2006, Issue 3 (see www.thecochranelibrary.com for information). Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. The results of a Cochrane review can be interpreted differently, depending on people’s perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of review authors, and are not necessarily shared by The Cochrane Collaboration     

Spousal responses to prostate cancer: an integrative review

Prostate cancer is the most frequently diagnosed cancer in the United States. Survival rates of localized cancer are excellent, with more than 96 percent of men surviving 5 years after diagnosis. However, treatment such as radical prostatectomy may leave the patients and their spouses to deal with long-term side effects, including impotence and urinary incontinence. While previous studies have shown how men react to these treatment effects, studies are now emerging that focus on the responses of their spouses to diagnosis and treatment side effects. This integrative literature review examines the psychosocial responses of spouses whose husbands have undergone prostatectomy. Studies that report on spouses' responses to diagnosis, treatment, and side effects were reviewed. The literature shows that spouses are significantly more distressed overall than are patients. Sources of distress include lack of information, fear of the unknown, fear of what the future will hold, and treatment-related concerns. Only one controlled intervention study was found that attempted to address these concerns. Further controlled studies are needed to address spousal distress.     

A review of African American-white differences in risk factors for cancer: prostate cancer

Objective  

African American men have higher prostate cancer incidence rates than White men, for reasons not completely understood. This review summarizes the existing literature of race-specific associations between risk factors and prostate cancer in order to examine whether associations differ.     

High-intensity focused ultrasound for prostate cancer: a systematic review

High-intensity focused ultrasound (HIFU) has recently been promoted as a non-invasive treatment option for prostate cancer. This systematic review sought to evaluate the evidence comparing it with standard treatment in patients with localised prostate cancer. The literature review included searches of MEDLINE, EMBASE, the Cochrane Library, annual meetings’ abstracts and websites of evidence-based practice guideline producers. Studies were included if they were randomised controlled trials comparing HIFU with current management approaches, or were meta-analyses, systematic reviews or practice guidelines addressing HIFU. No randomised controlled trials or meta-analyses were identified. Seven systematic reviews and two practice guidelines were identified; neither contained randomised controlled trials. Adjusting the selection criteria to include case series found 34 clinical studies of HIFU. Twenty-nine evaluated HIFU as the primary treatment and five examined HIFU as salvage treatment for recurrence after radiotherapy. In most studies the outcomes used to determine efficacy were negative biopsy rates or prostate-specific antigen (PSA) levels. Among the 29 studies of HIFU as the primary treatment, negative biopsy rates ranged from 35 to 95% in 21 studies, a PSA nadir of ≤0.5 ng/ml ranged from 55 to 91% in 10 studies and mean PSA nadirs ranged from 0 to 1.9 ng/ml in 17 studies. Five studies reported 5-year disease-free survival rates ranging from 55 to 95%. Among five studies of HIFU as salvage treatment, negative biopsy rates ranged from 73 to 84% in four studies, a PSA nadir of ≤0.5 ng/ml ranged from 57 to 66% in three studies and mean PSA nadirs were 1.97 and 2.38 ng/ml in two studies, respectively. Current evidence on HIFU use in prostate cancer patients is of low quality, rendering it difficult to draw conclusions about its efficacy. Until results from case series are confirmed in prospective studies, the widespread use of HIFU is not supported.     

Second-line therapy for castrate-resistant prostate cancer: a literature review

Despite a survival benefit in the first-line treatment of castrate-resistant prostate cancer (CRPC) with docetaxel, the prognosis remains limited. There are increasing options available for patients with CRPC in the second-line setting, but there is currently little consensus regarding the optimal treatment. There have been numerous phase II and retrospective studies examining second-line options in CRPC, including retreatment with docetaxel, mitoxantrone, cyclophosphamide and carboplatin, which can be associated with meaningful responses in a significant minority of patients. In 2010 three randomized trials were published or presented which demonstrated a survival benefit in the second-line setting. These included cabazitaxel compared with mitoxantrone, sipuleucel-T (immunotherapy) and abiraterone acetate versus placebo. Ongoing research in the second-line setting of CRPC to optimize treatment options, with the objectives of survival prolongation, improvement in quality of life and pain management, is still needed.     

Focal therapy in prostate cancer: A review of seven common controversies

Radical treatments such as prostatectomy and radiotherapy have demonstrated success in terms of biochemical and disease-specific survival for localised prostate cancer. However, whilst the end goal of any cancer treatment is to control or cure disease it must also do so by minimising any side effects that may be experienced by the patient. Focal therapy as a concept aims to redress this established therapeutic ratio by treating areas of the prostate affected by significant disease as opposed to treating the entire gland. However, there are a number of common criticisms of focal therapy – we deem the seven sins – that require further interrogation.     

Management of gynaecomastia in patients with prostate cancer: a systematic review

Patients with prostate cancer are increasingly being offered treatment with non-steroidal antiandrogen monotherapy, which offers potential quality-of-life benefits compared with other treatment. Non-steroidal antiandrogens directly antagonise androgen action in breast tissue, and indirectly increase the oestrogen concentration. Thus, the most troublesome side-effects of monotherapy with these drugs are gynaecomastia and breast pain. Patients younger than 60 years of age, who might not have symptoms of prostate cancer, are probably more concerned about their body image and the development of enlarged breasts than are those older than 60 years. Clinicians who seek a treatment for prostate cancer need information on simple and well-tolerated options for the management of gynaecomastia and breast pain. In this review, management options for gynaecomastia caused by hormonal manipulation in patients with prostate cancer are discussed.     

Parenteral oestrogen in the treatment of prostate cancer: a systematic review

The objectives of this study were to assess the effectiveness and safety of parenteral oestrogen in the treatment of prostate cancer, and to examine any dose relationship. A systematic review was undertaken. Electronic databases, published paper and internet resources were searched to locate published and unpublished studies with no restriction by language or publication date. Studies included were randomised controlled trials of parenteral oestrogen in patients with prostate cancer; other study designs were also included to examine dose-response. Study selection, appraisal, data extraction and quality assessment were performed by one reviewer and independently checked by another. Twenty trials were included in the review. The trials differed with regard to the included patients, formulation and dose of parenteral oestrogen, comparator used, outcome measures reported and the duration of follow-up. The results provide no evidence to suggest that parenteral oestrogen, in doses sufficient to produce castrate levels of testosterone, is less effective than luteinising hormone-releasing hormone (LHRH) or orchidectomy in controlling prostate cancer, or that it is consistently associated with an increase in cardiovascular mortality. Further well-conducted trials of parenteral oestrogen are required. A pilot randomised controlled trial comparing transdermal oestrogen to LHRH analogues in men with locally advanced or metastatic prostate cancer is underway in the United Kingdom.