The Role of Targeted Focal Therapy in the Management of Low-Risk Prostate Cancer: Update on Current Challenges

Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, there has been a sharp increase in annual prostate cancer incidence. Cancer-specific mortality, though, is relatively low. The majority of these cancers will not progress to mortal disease, yet most men who are diagnosed opt for treatment as opposed to observation or active surveillance (AS). These men are thus burdened with the morbidities associated with aggressive treatments, commonly incontinence and erectile dysfunction, without receiving a mortality benefit. It is therefore necessary to both continue investigating outcomes associated with AS and to develop less invasive techniques for those who desire treatment but without the significant potential for quality-of-life side effects seen with aggressive modalities. The goals of this paper are to discuss the problems of overdiagnosis and overtreatment since the advent of PSA screening as well as the potential for targeted focal therapy (TFT) to bridge the gap between AS and definitive therapies. Furthermore, patient selection criteria for TFT, costs, side effects, and brachytherapy template-guided three-dimensional mapping biopsies (3DMB) for tumor localization will also be explored.

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Prostate-specific antigen and biomarkers for prostate cancer

10.1093/med/9780199659579.003.0061 ◽

2017 ◽

Author(s):

Hans Lilja

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Opportunistic Screening ◽

High Risk Prostate Cancer ◽

Psa Testing ◽

Risk Prostate Cancer ◽

Low Risk Prostate Cancer ◽

Prostatic Diseases ◽

Significant Disease

Prostate-specific antigen (PSA) is a kallikrein serine protease secreted by the prostate to liquefy the ejaculatory coagulum. Changes in the blood/prostate barrier allows PSA to enter the circulation in men with prostate cancer and other inflammatory prostatic diseases. The commonest method for detection of men at risk of prostate cancer is PSA testing, which is typically used in an opportunistic screening setting. The widespread use of PSA testing leads to overdiagnosis and overtreatment of many men with low-risk prostate cancer, but can allow the identification of those with significant disease requiring radical treatment. This lack of specificity for high-risk prostate cancer has led to the need for more accurate biomarkers or methods to improve the use of PSA testing.

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Overtreatment of low-risk prostate cancer in the United States: Incidence, cost, complications, and implications for the screening debate.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.161 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 161-161 ◽

Cited By ~ 1

Author(s):

Ayal A. Aizer ◽

Xiangmei Gu ◽

Toni K. Choueiri ◽

Neil E. Martin ◽

Jim C. Hu ◽

...

Keyword(s):

Prostate Cancer ◽

United States ◽

Life Expectancy ◽

Specific Antigen ◽

Expectant Management ◽

The United States ◽

Low Risk ◽

Definitive Treatment ◽

Risk Prostate Cancer ◽

Low Risk Prostate Cancer

161 Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance as the sole option for men with low-risk prostate cancer (LRPC) and a life expectancy <10 years. We sought to describe the incidence, risk factors, cost, and morbidity related to overtreatment of LRPC within the United States. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare Program to identify 11,744 men ≥66 years with LRPC diagnosed from 2004-2007. Expected survival was estimated using the 2007 Social Security Life Table and was increased and decreased by 50% in men in the upper and lower quartiles of comorbidity, respectively, as specified by the NCCN. Overtreatment was definitive treatment in men with LRPC and life expectancy <10 years. Costs were the amount paid by Medicare in the year following minus the year prior to diagnosis. Toxicities were defined as relevant Medicare diagnoses or interventions. Results: Of 3001 men with LRPC and a life expectancy <10 years, 2011 (67%) were treated definitively. On multivariable logistic regression, men overtreated for prostate cancer were more likely to be younger (p<.001), white (vs black, OR 1.44, 95% CI 1.03-2.02, p=.03), married (OR 1.30, 95% CI 1.05-1.61, p=.02), urban (trend, OR 1.40, 95% CI 0.98-2.00, p=.06), have higher Elixhauser comorbidity (p<.001), and have a higher clinical stage (T2 vs T1, OR 1.57, 95% CI 1.19-2.07, p=.001) and prostate-specific antigen level (OR 1.02, 95% CI 1.02-1.02, p<.001). Relative to expectant management, the mean added cost per definitive treatment was $15,308. When extrapolated nationally the cumulative net cost of overtreatment in men ≥66 years is $32 million per annum. Long-term urinary, erectile, and bowel toxicity occurred in 59.2% and 50.0%, 47.9% and 19.7%, and 7.1% and 17.8% of prostatectomy and radiation patients, respectively. Conclusions: Overtreatment of prostate cancer is partially driven by sociodemographic factors and occurs in a high percentage of men with LRPC and limited life expectancy, with marked impact on patient quality of life and health care costs. Efforts to enhance appropriate management of LRPC would reduce the harms associated with screening.

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Radiotherapeutic Strategies in the Management of Low-Risk Prostate Cancer

The Scientific World JOURNAL ◽

10.1100/tsw.2010.179 ◽

2010 ◽

Vol 10 ◽

pp. 1854-1869 ◽

Cited By ~ 2

Author(s):

Kevin S. Choe ◽

Stanley L. Liauw

Keyword(s):

Prostate Cancer ◽

Tumor Imaging ◽

Early Stage ◽

External Beam Radiotherapy ◽

Specific Antigen ◽

The United States ◽

Low Risk ◽

Image Guided Radiotherapy ◽

Risk Prostate Cancer ◽

Low Risk Prostate Cancer

Prostate cancer is the most common nonskin malignancy among men in the United States. Since the introduction of screening with prostate-specific antigen (PSA), most patients are being diagnosed at an early stage with low-risk disease. For men with low-risk prostate cancer, there exists an array of radiotherapeutic strategies that are effective and well tolerated, such as external-beam radiotherapy and brachytherapy. In recent years, there have been tremendous advances in the field of radiation oncology that have transformed the way radiation is used to treat prostate cancer, such as intensity-modulated radiotherapy, image-guided radiotherapy, and stereotactic radiotherapy. It is now feasible to deliver high doses of radiation to the target volume with improved precision and spare more of the neighboring tissues from potentially damaging radiation. Disease outcomes are generally excellent in low-risk prostate cancer. Improvements are expected with further integration of innovative technologies in radiation delivery, tumor imaging, and target localization.

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Three-dimensional conformal external beam radiotherapy compared with permanent prostate implantation in low-risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and prostate-specific antigen level

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2005.11.037 ◽

2006 ◽

Vol 65 (1) ◽

pp. 65-72 ◽

Cited By ~ 35

Author(s):

Barby Pickett ◽

John Kurhanewicz ◽

Jean Pouliot ◽

Vivian Weinberg ◽

Katsuto Shinohara ◽

...

Keyword(s):

Prostate Cancer ◽

External Beam Radiotherapy ◽

Specific Antigen ◽

Three Dimensional ◽

Resonance Spectroscopy ◽

External Beam ◽

Antigen Level ◽

Risk Prostate Cancer ◽

Low Risk Prostate Cancer ◽

Magnetic Resonance Spectroscopy Imaging

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Magnetic Resonance–Guided Prostate Ablation

Seminars in Interventional Radiology ◽

10.1055/s-0039-1697001 ◽

2019 ◽

Vol 36 (05) ◽

pp. 351-366

Author(s):

David A. Woodrum ◽

Akira Kawashima ◽

Krzysztof R. Gorny ◽

Lance A. Mynderse

Keyword(s):

Prostate Cancer ◽

Prediction Models ◽

Focal Therapy ◽

The United States ◽

Management Approach ◽

Low Grade ◽

Intermediate Risk ◽

Screening Programs ◽

Risk Prostate Cancer ◽

Prostate Cancers

AbstractIn 2019, the American Cancer Society (ACS) estimates that 174,650 new cases of prostate cancer will be diagnosed and 31,620 will die due to the prostate cancer in the United States. Prostate cancer is often managed with aggressive curative intent standard therapies including radiotherapy or surgery. Regardless of how expertly done, these standard therapies often bring significant risk and morbidity to the patient's quality of life with potential impact on sexual, urinary, and bowel functions. Additionally, improved screening programs, using prostatic-specific antigen and transrectal ultrasound-guided systematic biopsy, have identified increasing numbers of low-risk, low-grade “localized” prostate cancer. The potential, localized, and indolent nature of many prostate cancers presents a difficult decision of when to intervene, especially within the context of the possible comorbidities of aggressive standard treatments. Active surveillance has been increasingly instituted to balance cancer control versus treatment side effects; however, many patients are not comfortable with this option. Although active debate continues on the suitability of either focal or regional therapy for the low- or intermediate-risk prostate cancer patients, no large consensus has been achieved on the adequate management approach. Some of the largest unresolved issues are prostate cancer multifocality, limitations of current biopsy strategies, suboptimal staging by accepted imaging modalities, less than robust prediction models for indolent prostate cancers, and safety and efficiency of the established curative therapies following focal therapy for prostate cancer. In spite of these restrictions, focal therapy continues to confront the current paradigm of therapy for low- and even intermediate-risk disease. It has been proposed that early detection and proper characterization may play a role in preventing the development of metastatic disease. There is level-1 evidence supporting detection and subsequent aggressive treatment of intermediate- and high-risk prostate cancer. Therefore, accurate assessment of cancer risk (i.e., grade and stage) using imaging and targeted biopsy is critical. Advances in prostate imaging with MRI and PET are changing the workup for these patients, and advances in MR-guided biopsy and therapy are propelling prostate treatment solutions forward faster than ever.

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