Identifying and assessing progression in prostate cancer
Learn about identifying and assessing disease progression in prostate cancer and about scanning for PSMA.
This site is intended for healthcare professionals outside of the United States (US) and the United Kingdom (UK).
This site is created and funded by Novartis.
Recognizing disease progression in prostate cancer is crucial to help improve disease management, as it provides an opportunity to refine treatment approaches. To identify disease progression in prostate cancer, it is crucial to evaluate the cancer stage, employ next-generation imaging techniques, and assess relevant biomarkers to monitor the course of the disease.
Recognizing disease progression in prostate cancer is crucial to help improve disease management, as it provides an opportunity to refine treatment approaches. To identify disease progression in prostate cancer, it is crucial to evaluate the cancer stage, employ next-generation imaging techniques, and assess relevant biomarkers to monitor the course of the disease.
Identifying prostate cancer disease states
Prostate cancer can be classified into various disease states or stages based on the extent and severity of the cancer. The most commonly used staging system for prostate cancer is the tumor, node, metastasis (TNM) staging system that considers1a:
- The size and extent of the primary tumor (T-staging)
- The involvement of nearby lymph nodes (N-staging)
- The presence of distant metastasis (M-staging)
The most common disease states in prostate cancer include2 3 4:
Localized prostate cancer:
The tumor is confined to the prostate gland. Over time, the tumor may grow or spread but remains within the prostate.
Locally advanced prostate cancer:
The tumor extends beyond the prostate gland and may have invaded locoregional structures such as the seminal vesicles, rectum, bladder, or lymph nodes close to the prostate.
Metastatic prostate cancer:
The tumor spreads to other parts of the body, including lymph nodes, bones, and distant organs such as the lungs.
All stages require close monitoring and ongoing treatment to manage the disease and maintain the best possible quality of life for the patient.1b
-
Progression to metastatic prostate cancer
-
Progression to castration-resistant prostate cancer (CRPC)
Overtime, locally advanced prostate cancer can progress to metastatic prostate cancer. Patients are especially at risk of progression if there is evidence of biochemical recurrence (BCR).
BCR is defined as increasing prostate-specific antigen (PSA) levels following treatment.This increase in PSA suggests that cancer may still be present and is a sign that the disease is still progressing. Those experiencing BCR have an increased risk of developing metastases and mortality due to prostate cancer.1c 5 6
The progression to metastatic prostate cancer involves several key stages:
Local invasion:
As prostate cancer advances, malignant cells may infiltrate nearby structures such as the seminal vesicles, bladder, and rectum.
Perineural invasion:
The primary mechanism as to which carcinoma penetrates the capsule and metastasizes.
Lymph node involvement:
Prostate cancer metastasis often spreads to pelvic lymph nodes, facilitated by perineural and lymphatic pathways.
Bone metastasis:
Prostate cancer cells can spread to bones particularly through the vertebral venous system.
CRPC is a stage of prostate cancer in which the disease progresses despite medical or surgical interventions that reduce the levels of male hormones (testosterone) to a “castrate state.” CRPC is defined by a rise in PSA levels, showing biochemical progression, and may also involve radiographic progression, where the cancer spreads to other areas of the body.
Androgen deprivation therapy (ADT) can induce remission of prostate cancer. However, a large proportion of these patients will, over time, develop castration-resistant disease despite an initial response to ADT.7a
There are several mechanisms that underlie the pathogenesis of progression to CRPC7b 8:
- Androgen receptor (AR) amplification
- AR bypass
- Enzyme modulation
Patients with CRPC have a poor prognosis, with most developing painful bone metastases. The median survival of patients with CRPC is approximately 14 months.9 Thus, a multidisciplinary approach involving urologists, medical oncologists, clinical oncologists, nurses, psychologists, and social workers is necessary for the management of patients with mCRPC.1d
Symptoms of prostate cancer progression
Signs and symptoms of progression in prostate cancer can vary depending on the stage of the disease and the areas where the cancer has spread.
Common signs of progression include the following10 11:
Worsening urinary symptoms*
Hematuria
Hematospermia
Pelvic pain or discomfort
Erectile dysfunction
Bone pain, especially in the spine, hips, and ribs
Neurological symptoms**
Fatigue
*such as nocturia.
**such as weakness, numbness, or problems with bowel/bladder control.
Next-generation imaging aims to better risk-stratify patients with advanced prostate cancer. Radiological evaluation provides an objective measurement of the size of the tumor and detects new lesions. One or more of the following imaging modalities may be used in patients with advanced prostate cancer12b 13b:
PET
Positron emission tomography (PET) involves the administration of a small radioactive “tracer”. This is injected into a vein and finds its way to the prostate cancer cells. The cancer cells are then detected by a PET scanner, followed by a computation of a digital image that represents the distribution of the radiotracer in the body. In modern practice, PET is almost always combined with computed tomography (CT) or molecular resonance imaging (MRI) scanning.
PET/CT
PET/CT is a diagnostic imaging procedure that combines PET with CT. It provides detailed, three-dimensional images that show the location and metabolic activity of prostate cancer cells. They are often used to detect metastases to lymph nodes, bones, or other areas, helping in staging and treatment planning. They are particularly effective when a specific radiotracer targeting prostate-specific membrane antigen (PSMA) is used, as it enhances the detection of prostate cancer lesions.
PET/MRI
PET/MRI is an advanced medical technique where PET and MRI techniques are combined into a single imaging session using a hybrid scanner that generates detailed anatomical images from the MRI and functional information from the PET. This provides a comprehensive view of the prostate, helping in the detection and staging of cancer, evaluation of treatment response, and identification of potential metastases all in a single imaging session, which can aid in more accurate diagnosis and treatment planning.
WB-MRI
Whole-body magnetic resonance imaging is a non-invasive diagnostic technique that provides a comprehensive view of the entire body, including the prostate, to detect metastatic spread to the bones and other areas. It is useful for staging, monitoring treatment response, and identifying metastases in advanced cases of prostate cancer.
Biomarkers provide an indication of disease progression.
Prostate-specific antigen (PSA)14 15a:
PSA is a serine protease enzyme produced by the columnar epithelium of prostatic tissue. A higher level of PSA is associated with a risk of PSA progression
Prostate-specific membrane antigen (PSMA)15b 16 17:
PSMA is a protein expressed in tissues such as the salivary glands, small intestine, and the kidneys, but it is predominately found in prostate tissue. The expression level of PSMA is higher in prostate cancer cells when compared with healthy tissue cells
Since PSMA is present in a high percentage of prostate cancer patients, it is arising as an interesting diagnostic biomarker and also as a therapeutic target such as in PSMA-targeted radioligand therapy
Scanning for PSMA
PSMA scanning involves introducing a radioactive tracer into the bloodstream. This tracer homes in on the PSMA protein highly expressed in prostate cancer cells. A PET/CT scanner then captures images of the entire body to pinpoint locations where the tracer has attached to the PSMA protein.15c
The results of PSMA PET/CT diagnosis are valuable for determining if prostate cancer has spread throughout the body and providing crucial information about the extent of the metastasis. These data enable healthcare professionals to customize clinical management for individuals, including the selection of patients with metastatic prostate cancer who may benefit from PSMA-directed therapy.18
Identifying disease progression is essential to help improve patient outcomes, as it offers an opportunity to modify treatment strategies and potentially leading to the maintenance of the quality of life for the patient.
Our all-encompassing service designed to simplify the adoption of RLT and minimize time to treatment
Abbreviations
ADT, androgen deprivation therapy
AR, androgen receptor
BCR, biochemical recurrence
CRPC, castration-resistant prostate cancer
CT, computed tomography
mCRPC, metastatic castration-resistant prostate cancer
MRI, magnetic resonance imaging
PET, positron emission tomography
PSA, prostate-specific antigen
PSMA, prostate-specific membrane antigen
RLT, radioligand therapy
TNM, tumor, node, metastasis
WB-MRI, whole-body MRI
References
1a 1b 1c 1d Cornford P, Tilki D, van den Bergh RCN, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer. European Association of Urology; 2024.
2 Cancer Research UK. Localised prostate cancer. Updated May 31, 2022. Accessed July 19, 2024. https://www.cancerresearchuk.org/about-cancer/prostate-cancer/stages/localised-prostate-cancer
3 Cancer Research UK. Locally advanced prostate cancer. Updated May 31, 2022. Accessed July 19, 2024. https://www.cancerresearchuk.org/about-cancer/prostate-cancer/stages/locally-advanced-prostate-cancer
4 Cancer Research UK. What is metastatic prostate cancer? Updated February 15, 2023. Accessed July 19, 2024. https://www.cancerresearchuk.org/about-cancer/prostate-cancer/advanced-cancer/about-advanced-cancer
5 Hammerich KH, Ayala GE, Wheeler TM. Anatomy of the prostate gland and surgical pathology of prostate cancer. In: Hricak H, Scardino P, eds. Prostate Cancer. Contemporary Issues in Cancer Imaging. Cambridge: Cambridge University Press, 2009:1-14.
6 Wang C, Shen Y, Zhu S. Distribution features of skeletal metastases: A comparative study between pulmonary and prostate cancers. PLoS One. 2015;10(11):e0143437. doi:10.1371/journal.pone.0143437
7 Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene. 2013;32(49):5501-5511. doi:10.1038/onc.2013.206
8 Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4(3):365-380. doi:10.3978/j.issn.2223-4683.2015.05.02
9 Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180-1192. doi:10.1111/j.1742-1241.2011.02799.x
10 Leslie SW, Soon-Sutton TL, R I A, Sajjad H, Siref LE. Prostate Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 30, 2023.
11 Cancer Research UK. Symptoms of metastatic prostate cancer. Updated July 20, 2022. Accessed July 19, 2024. https://cancerresearchuk.org/about-cancer/prostate-cancer/metastatic-cancer/symptoms
12a 12b Trabulsi EJ, Rumble RB, Jadvar H, et al. Optimum imaging strategies for advanced prostate cancer: ASCO guideline. J Clin Oncol. 2020;38(17):1963-1996. doi:10.1200/JCO.19.02757
13a 13b Winfield JM, Blackledge MD, Tunariu N, Koh DM, Messiou C. Whole-body MRI: a practical guide for imaging patients with malignant bone disease. Clin Radiol. 2021;76(10):715-727. doi:10.1016/j.crad.2021.04.001
14 Darwish OM, Raj GV. Management of biochemical recurrence after primary localized therapy for prostate cancer. Front Oncol. 2012;2:48. doi:10.3389/fonc.2012.00048
15a 15b 15c Jiang J, Tang X, Pu Y, et al. The value of multimodality PET/CT imaging in detecting prostate cancer biochemical recurrence. Front Endocrinol (Lausanne). 2022;13:897513. doi:10.3389/fendo.2022.897513
16 Hupe MC, Philippi C, Roth D, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol. 2018;8:623. doi:10.3389/fonc.2018.00623
17 Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
18 Fendler WP, Ferdinandus J, Czernin J, et al. Impact of 68Ga-PSMA-11 PET on the management of recurrent prostate cancer in a prospective single-arm clinical trial. The Journal of Nuclear Medicine. 2020;61(12):1793-1799. doi:10.2967/jnumed.120.242180
Get in touch
Our dedicated RLT specialist teams aim to streamline care coordination and alleviate uncertainty, ensuring you and your patients feel confident and supported every step of the way.