What is Radiation Therapy? Radiation is the strategic use of ionizing radiation or photons to kill cancer cells. The targeted cells die without growing or replicating themselves. Radiation therapy, like surgery, is Radical Prostatectomy Removing the entire prostate gland through surgery, known as a radical prostatectomy, is a common option for men whose cancer has not spread. For men with advanced or recurrent disease, other surgical procedures may be chosen, such as removal of lymph nodes, which are Primary hormone therapy also called androgen deprivation therapy or ADT is part of the standard of care for advanced metastatic prostate cancer.
ADT is designed How well chemotherapy is likely to be tolerated. What prior therapies you have received. If radiation is needed prior to What is Active Surveillance? The concept of Active Surveillance has increasingly emerged as a viable option for men who decide not to undergo immediate radical treatment for prostate cancer surgery or radiation therapy. Active Surveillance is based on the concept that low-risk prostate cancer is unlikely What is Precision Medicine?
The promise of precision medicine is this: someday, there will be no trial and The immune system has the remarkable ability to kills cells that can cause harm, such as infected cells or cancer cells. A phase 1 dose-escalation clinical trial of hyperpolarized 13 C-labeled pyruvate in prostate cancer patients is planned for [ 44 ]. DWI is based on the diffusion properties of water within tissue. Regions of prostate cancer show increased cell density and reduced apparent diffusion coefficient ADC relative to normal prostate [ 45 ].
The biologic significance of diffusion, however, is unclear. Although the technology has shown high resolution, further validation in larger trials is required. After injecting a gadolinium chelate contrast agent, areas of hypervasculature such as prostate cancer show rapid enhancement and early washout of signal intensity. However, some prostate cancers are not detectable by this method because of low vascularity. For DCE-MRI results to be comparable among studies from different institutions, a standardized technique and analytic tools need to be further developed.
The most appealing aspect of these MRI techniques is an ability to conduct a single comprehensive multiparametric MRI examination that integrates all data acquisitions relevant to cancer diagnosis, staging, and characterization. In this way, the overall diagnostic performance of MRI is expected to improve.
FDG PET was incapable of differentiating prostate cancer from benign hyperplasia [ 16 ] or detecting pelvic lymph node metastases [ 50 ]; other studies reported good accuracy in detecting primary or locally recurrent prostate cancer [ 17 , 18 ]. As noted, the utility of PET and SPECT to detect locally confined prostate cancer will be improved by molecular probes with higher sensitivity and specificity. Early results are promising, with increasing interest in 18 F-choline for lesion detection [ 23 ]. Other investigational imaging methods— Raman spectroscopy is an optical imaging technique to measure the properties of molecules in the tissue.
The technology has only been tested on tissue specimens in vitro; thus, its clinical utility is unclear.
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Another investigational imaging technique is smart-needle optical scattering spectroscopy to probe tissue of interest in real time to identify the presence of cancer. If validated, this technology potentially could reduce the number of biopsies required for prostate cancer diagnosis. It could be used in combination with other imaging techniques for biopsy guidance. A drawback of the technology is that it is invasive. Clinical issues— Imaging as a predictive tool for patient outcomes can be successfully evaluated by comparing models that incorporate the outcome of imaging with models that do not to determine incremental predictive value.
The TNM staging system describes the extent of the primary tumor, the spread of tumor to nearby lymph nodes and glands, and the presence or absence of distal metastasis. In the United States, emphasis is placed on the T and N stages for initial prostate cancer staging because relatively few patients present with metastatic disease.
However, detecting extracapsular extension and locating the intraprostatic extent of disease are important issues in disease management. The incidence of extracapsular extension, particularly early microscopic extracapsular extension, is unknown. Statistically, patients with pathologic extracapsular penetration tend to have relatively worse year disease-free survival than patients with organ-confined disease; the significance of extracapsular extension requires investigation to determine what findings could be seen from the imaging perspective. Knowing the lymph node status helps to inform decisions on therapy, predict recurrence, and assess prognosis.
Imaging has not been reliable in identifying lymph node disease; until recently, lymph node size was the only widely used method of ascertaining nodal disease. However, size criteria are limited in accuracy because of significant overlap between the size of normal and malignant nodes. The major challenge to improving staging technology is the need for improved pathologic markers. These markers serve as reference standards to find imaging techniques that predict patient outcomes and help guide therapy.
Other important issues remain, including knowing what patient cohorts benefit most from nodal imaging and staging and learning how the predictive value of an accurate technique affects therapeutic options. It was applied ad hoc with limited success. The patient would be diagnosed with stage A1 prostate cancer after transurethral resection of the prostate and there would be nonstandardized follow-up. Contemporary active surveillance includes low-risk patients with low tumor volumes, low PSA levels, and low Gleason scores. Follow-up is standardized, patients are well informed, and periodic repeat prostate biopsies are performed.
Although active surveillance may not be advised for all men, in general, it is underused. Localized, unifocal cancer of clinical significance is usually considered the prerequisite for successful focal therapy. However, unilateral multifocal but all on one side disease may make performing focal therapy easier.
With multifocal cancer, a dominating index lesion probably drives progression; thus, the cancer may be considered biologically unifocal disease. Focal tumor ablation is feasible with low morbidity. The problem is localizing suitable tumors and monitoring tissue ablation. In addition to identifying patients who are candidates for focal therapy, imaging may play a role in identifying the target lesion.
An important issue is relating the target delivery device to the imaging technique to deliver treatment to the target. Another critical issue with focal therapy is residual PSA, which makes posttherapy follow-up more challenging.
The biologic potential of not treating missed secondary tumors and the role of adjuvant therapy are additional issues. Active surveillance remains debated because of the lack of adequate modern randomized controlled trials and lack of robust imaging. There are clearly social and economic factors that impact the use of active surveillance. A major concern with current protocols of active surveillance remains the limited ability to closely and noninvasively monitor tumor progression within the prostate gland.
Challenges in Prostate Cancer Treatment
Imaging is well poised to address this concern, and imaging integration may improve general acceptance of active surveillance in the management of low-risk disease. Outcomes of local therapy, whether delivered up front or delayed after active surveillance, stand to improve with integration of imaging guidance. Standard-care therapeutic options include radical prostatectomy, high-dose external beam radiotherapy, and brachytherapy, used alone or in combination. As a first step, recommending the most appropriate therapeutic technique depends on accurate staging and prognostication of disease.
Ultimately, the objective of local therapy is to control disease with minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Because of the historical inability to accurately visualize the local extent of disease, all local therapeutic interventions were simply targeted to the prostate gland as a surrogate for cancer.
This paradigm has invariably led to both over- and undertreatment of low-burden and locally extensive disease, respectively. In this manner, visualizing the location and extent of disease burden stands to more appropriately guide the execution of both surgery and radiation delivery. Visualizing disease that extends beyond the prostate gland could reduce the incidence of incomplete cancer resections and modify radiation delivery to include extraprostatic disease.
Similarly, prostatic subsites of tumor burden can be focally selected for radiation dose intensification to improve cancer control and reduce unnecessary dose exposure to adjacent organs at risk of injury and subsequent toxicity. It is important to recognize that the radiation dose required to control microscopic disease is much lower than that required to control gross dense disease, and modulation of dose intensity on the basis of spatial distribution of disease burden has yet to be fully explored. Focal ablative approaches do not deliver therapy to regions bearing microscopic disease within and around the prostate gland, which may impact cancer control.
To address this concern, adjuvant therapies to focal ablation may be considered. In fact, immediate radiotherapy to presumed residual microscopic disease after prostatectomy has recently been shown to improve overall survival in patients with localized prostate cancer. Imaging techniques that could monitor progression of microscopic disease may obviate adjuvant local therapies altogether, restricting their use to the salvage of microscopic progression. Role of imaging— The incremental predictive accuracy of imaging is of great interest in prostate cancer.
However, before this can be determined, imaging technology must be more mature, stable, and standardized.
MRI has been useful in identifying prostate cancer on the basis of reduced T2 signal intensity, increased choline, and decreased citrate and spermine [ 52 ]. Improved tumor localization and lymph node staging can be achieved by combining molecular imaging with registration to anatomic CT and MR image sets [ 21 ]. In addition, validating intraprostatic biologic target volumes using in vivo fiducial markers has been shown to be feasible [ 53 ].
The correlated histopathology and marker placement system uniquely correlates pathology data for molecular image validation and discrete dose intensification, targeting tumor while sparing normal radiosensitive tissues urethra, rectum, and neurovascular bundle. The correlated histopathology and marker placement system protocol showed clinical feasibility as a validation method for molecular imaging techniques such as SPECT-CT. Techniques to directly integrate images in the offline and online guidance of local therapies are currently being developed and tested for technical performance.
Prostate Cancer Treatment
These include techniques for image display, registration, navigation, and online adaptation to movements and deformations that occur throughout the therapeutic intervention [ 54 , 55 ]. DCE-MRI of the prostate gland has also provided useful information for prostate cancer detection and staging [ 56 ].
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DWI uses diffusion constants to map the intraprostatic extent of cancer. The data are integrated into models to predict cancer localization [ 57 ]. Lymphotropic nanoparticle-enhanced imaging, a promising technique for malignant nodal evaluation, is highly accurate for nodal staging in patients with various primary cancers [ 59 ]. It evaluates nodal macrophage function and does not rely on nodal size to detect metastatic disease.
The software module MRProstateCare Image Guided Prostate Therapy Core was created for use with Slicer open-source software , a computerized surgical navigation platform to help plan, control, and direct prostate biopsies [ 54 , 55 ]. MrBot URobotics , a robot, was created to provide imaging-guided access to the prostate gland [ 60 ]. The robot is customized for transperineal needle insertion and designed to be compatible with MRI.
It can accommodate various needle drivers for different percutaneous interventions, such as biopsy, thermal ablation, or brachytherapy. TRUS-guided radiofrequency ablation involves ultrasound monitoring of the thermoablative technique. Several problems are associated with radiofrequency ablation in the prostate.
The distributed energy is prone to variation because of heat sink by vasculature and is diffused over a wide area, making the temperature of adjacent organs difficult to control; and heating is slow, often resulting in insufficient apex ablation. There is also poor geometric correlation between the target lesion and energy input. Additionally, the procedure is difficult to monitor intraoperatively.