To view this page ensure that Adobe Flash Player version 11.1.0 or greater is installed.
State of the Art in Locally Advanced and
Recurrent Non-metastatic Prostate Cancer
Hema Vankayala, MD 1 and Ulka Vaishampayan, MD 2
1. Medical Oncologist, John D Dingell VA Medical Center, Wayne State University, Detroit; 2. Professor of Oncology, Karmanos Cancer Institute,
Wayne State University, Detroit, US
Abstract Prostate cancer (PC) is the second leading cause of cancer-related death in men in the US. Biochemical relapse is a significant problem, due to
the eventual progression to metastatic disease. It is also an opportunity to explore interventions that may have the potential to prevent or delay
the occurrence of metastases. Multiple therapies with diverse mechanisms of action have become available for use in metastatic castrate-
resistant PC and are currently under active investigation in the non-metastatic disease state. The intent of this article is to discuss currently
approved therapy in localized and locally advanced PC and to review the state of the art in clinical management within this disease state. We
also discuss the novel agents and targets in development, especially for recurrent, non-metastatic PC.
Keywords Prostate cancer, PSA relapse, localized prostate cancer, locally advanced prostate cancer, castrate resistance
Disclosure: Hema Vankayala, MD, and Ulka Vaishampayan, MD, have no conflicts of interest to declare. No funding was received in the publication of this article.
Received: September 4, 2014 Accepted: October 20, 2014 Citation: Oncology & Hematology Review, 2014;10(2):123–32
Correspondence: Ulka Vaishampayan, MD, Professor of Oncology, Karmanos Cancer institute/Wayne State University, 4100 John R, 4233 HWCRC, Detroit MI 48201, US.
Prostate cancer (PC) is the second most common malignancy in American
men and the second leading cause of cancer-related death in men in the US.
It is estimated that in 2014 nearly 233,000 men will be diagnosed with PC,
with 29,480 dying from the disease. 1,2 The majority of them are diagnosed
as a result of screening, so symptomatic presentation is unusual. Since the
introduction of prostate-specific antigen (PSA) screening in US, more than
1.3 million men have been diagnosed with PC and one million of these have
undergone treatment. 3
Over 95 % of PCs are adenocarcinomas and the median age at diagnosis is
66 years. As per the Surveillance, Epidemiology, and End Results (SEER) 18
database, 80 % have localized disease and only 12 % have regional disease
at diagnosis. In the same database, 5-year survival rates vary significantly
with stage and have been noted to be 100 % for localized and regional
stage disease. The risk factors for PC are increasing age, African American
descent, and a family history of PC.
Localized Prostate Cancer
The current clinical management of localized PC depends on the risk
features associated with the cancer and a patient’s life expectancy. The
cancer risk is dependent on the clinical stage, PSA, highest Gleason Score
(GS), and disease burden. The prostate volume also affects the treatment
choice in some situations. Treatment options vary from watchful waiting
(WW) and active surveillance (AS), to radical prostatectomy (RP), external
© To u ch MEd ica l MEdia 201 4
beam radiation therapy (EBRT), brachytherapy, cryoablation, androgen
deprivation therapy (ADT), and high-intensity focused ultrasound.
Treatment recommendations and selection are dependent on disease
and patient characteristics, along with patient and physician preferences.
Several studies have shown that patients with low-grade, localized PC
have a low risk for clinical progression within the first 10 to 15 years of
diagnosis, so AS and WW are reasonable options. This strategy is also best
suited to men with a shorter life expectancy. 4–7
First-line ADT is seldom indicated in patients with localized PC. The
outcomes of men treated with primary ADT, compared with those who
were not, was evaluated in a large, retrospective cohort study. ADT is not
associated with increased risk for all-cause mortality, or with reduced
PC-specific mortality. However, the risk for PC progression on primary
ADT was not studied. The likely explanation for the 40 % decline in PC-
specific mortality during this time period is earlier detection and definitive
curative intervention. ADT is not curative. This study re-affirms that ADT
should be reserved for its established role: as palliation for metastatic
PC, in men with node-positive PC after RP, or in combination with RT in
intermediate- or high-risk PC. 8,9
The treatment options for low-risk and very-low-risk patients include AS,
WW, or monotherapies such as interstitial prostate brachytherapy, RT,