Prostate Cancer

Stage 3 Prostate Cancer

Prostate cancer can spread to nearby areas (stage III disease), including the seminal vesicles. Following a diagnosis of locally advanced prostate cancer, there a range of therapeutic options to treat the disease.

Hormone therapy, surgery, and radiation therapy are the primary treatments offered to men with stage III prostate cancer. In some cases, a combination of these therapies is required for an optimal outcome or to manage treatment resistance.

Here, we discuss the characteristics of stage III prostate cancer, the associated risk factors, its diagnosis, and treatment. We make significant contrasts with other prostate cancer stages to highlight the current challenges in the treatment of this stage of prostate cancer. 

What is prostate cancer?

Prostate cancer is a form of malignancy that starts in the prostate gland, a small gland located between the bladder and the penis. The prostate plays an essential role in normal sexual function and fertility.

As men age, the cells in this gland may transform into cancer cells that spread to other parts of the body (locally advanced disease). In the early stages of the disease, it develops slowly, while locally advanced diseases grow faster with an increased risk of distant spread.

Some men present with advanced disease that grows and spread more rapidly. Treatment resistance may develop in some patients, leading to lethal outcomes.  

Usually, clinicians use staging to describe the extent to which prostate cancer has advanced and spread to other organs. The three main stages include stages I (1), II (2), III (3), and IV (4).

An alphabetical notation is used to split some stages into levels of severity. When prostate cancer is stage 3, the tumor within the prostate gland has spread through the local tissues. This local spread often affects the seminal vesicles, two glands that secrete some of the fluid that make up the volume of semen.

What are the risk factors for prostate cancer?

The incidence of prostate cancer and the progression of advanced disease correlates with certain risk factors. The mechanisms underlying this association remains an active area of research.

However, it is now accepted that genetic, environmental, and social factors influence the risk of prostate cancer. For instance, race, age, and family history are strong predictors of a prostate cancer diagnosis (Crawford, 2003; Ferlay et al., 2010; Ferris-i-Tortajada et al., 2011). 

Over 20% of patients with prostate cancer have a first-degree relative with the disease, highlighting the importance of genetics. Further, increasing age is associated with a higher rate of the disease. Men over the age of 65-years of age are more likely to get a prostate cancer diagnosis than their younger counterparts.

Concerning race, black men are more likely to get a prostate diagnosis compared to men of other races. They are equally likely to be diagnosed with a more aggressive disease compared to men of other races. This increased risk may originate from the combinatory action of genetic, environmental, and social factors (Hatcher et al., 2009). However, the underlying mechanisms remain somewhat controversial.

Other factors, like chemical agents, influence the risk of several cancers. For prostate cancer, alcohol abuse and smoking increase the risk of prostate cancer. Notably, the risk of prostate cancer increases with the number of cigarettes smoked daily. A range of organic compounds (for example, insecticides) exhibits an association with prostate cancer risk, albeit weaker than alcohol and cigarettes.

Lifestyle is perhaps the strongest predictor of a prostate cancer diagnosis. Physical inactivity and calorie-rich diets increase the risk of prostate cancer (Barnard et al., 2008). The metabolic disorder arising from these lifestyle changes mediate sustained prostate inflammation to increase the risk of oxidative damage and prostate cancer.

TNM staging system

TNM staging is a system used by clinicians to classify the development of cancer in the body. Oncologists around the world use the size, location, and extent of spread to assign a grade to a prostate tumor.

The size (T), spread to local lymph nodes (N), and spread to distant tissues (M) are combined in the TNM system (American Joint Committee on Cancer) to derive a 4-tier grade for the tumor. The score for each element derives from a set of pre-determined criteria and thresholds.

These include the following stages:

  • Stage I – early-stage and slow-growing, which require no immediate treatment decisions.

  • Stage II – localized in the prostate with a risk of spreading to tissues around the prostate gland.

  • Stage III – advanced to nearby tissues with a risk of spreading to distant organs

  • Stage IV – advanced to distant organs with potentially fatal outcome.

What does stage 3 prostate cancer mean?

This stage of prostate cancer (called T3 or stage III) describes locally advanced disease. With stage III, the prostate cancer has spread to nearby tissues.

However, at stage III no other organs are affected except for local spread to the seminal vesicles. It is the stage before cancer invades nearby lymph nodes or other areas of the body, leading to stage IV cancer.

As stage IV is untreatable and difficult to manage, stage III often requires immediate treatment decisions to reduce the risk of progression.

Stage III prostate cancer is subdivided into three categories, depending on the extent of the local spread. These subgroups are:

  • T3a – Local spread to surrounding areas on one side of the prostate gland.

  • T3b – Local spread to nearby areas on both sides of the prostate.

  • T3c – Indicating local spread reaching one or both of the seminal vesicles.

Typically, Stage T3c has increased risk of developing into the last stage of prostate cancer, reaching nearby lymph nodes and potentially distant metastasis. Cancer cells in the lymph nodes can quickly spread to other parts of the body through the circulatory system.

What are the symptoms of stage 3 prostate cancer?

Because stage 3 prostate cancer is still within the prostate area and does not affect other body parts, symptoms majorly originate from the prostate gland and pelvic area. In some cases, patients may experience systemic symptoms and pain.

Stage 3 symptoms usually include urinary and sexual problems:

Urinary symptoms:

The expansion of the prostate gland due to cancer growth puts pressure on the bladder and the urethra. This pressure of nearby organs can cause urinary problems, including weak urine flow, frequent urination, urine retention, painful urination, and blood in the urine.

Sexual problems:

Because of the urinary complications associated with this stage of prostate cancer, some men experience a persistent urinary infection.  

Generally, the severity of these symptoms will vary between people and partly depend on the category of stage III (a-c) of cancer. Further, the symptoms may indicate other prostate conditions like prostatitis and benign prostatic hyperplasia.

Urinary tract infection:

Because of the urinary complications associated with this stage of prostate cancer, some men experience a persistent urinary infection.  

The severity of these symptoms will vary between people and partly depend on the category of stage III (a-c) of cancer. The symptoms may indicate other prostate conditions like prostatitis and benign prostatic hyperplasia. 

Diagnosis

The diagnosis of stage 3 prostate cancer is given after a battery of the test has been taken. They help determine the presence of cancer, the size of the tumor, the location in the gland, and the extent of spread to nearby tissues.

Your doctor may use the results of some or all of the following tests.

Prostate-specific antigen (PSA) test

PSA level can indicate the presence of cancer. Healthy prostate cells produce and a secret small amount of PSA in the blood. PSA level in the blood rises as the prostate enlarges, and the prostate integrity is damaged by cancer.

Digital rectal examination (DRE)

The doctor can investigate the presence of hard or lumpy areas through the wall of the rectum.

Magnetic resonance imaging (MRI) scan

MRI scan creates a detailed image of the prostate and the nearby tissues. This scan reveals the presence of cancer and informs the clinical decision for biopsy.

Prostate biopsy

A thin needle is used to extract small samples from the prostate. This tissue is investigated by a pathologist to check for cancer and determine its characteristics like the Gleason grade. Treatments for prostate cancer can only proceed after the analysis of a prostate biopsy.

Computerized tomography (CT) scan

This scan helps determine whether prostate cancer has spread to distant organs, especially nearby lymph nodes or bones.

Other tests

Some genetic tests are available to determine the risk of developing advanced diseases and the rate of metastasis.

Treatment 

Once the cancer is staged, the doctor will use this information in conjunction with other tests to make a treatment decision.

Currently, there is no single treatment that can robustly treat stage 3 prostate cancer. The appropriate treatment will depend on the individual case but will often involve one or a combination of the following treatments.

  • Hormone therapy – called androgen deprivation therapy. Hormone therapy aims to reduce the production or the utilization of androgens (testosterone) within the body. As prostate growth depends on androgens, ADT can shrink tumors and reduce their rate of growth. 

  • Surgery – radical prostatectomy to remove the prostate gland and surrounding tissues is another way to treat stage 3 prostate cancer. This procedure is suitable when cancer has not spread to distant organs, and the patient can undergo a major surgical procedure. Modern minimally invasive methods have been developed to help reduce the risks associated with traditional invasive prostatectomy. However, like any surgical procedure, these present with unique risks and side effects.

  • Radiation therapy – here, high energy rays can be used to destroy cancer cells within the prostate gland and reduce the rate of growth. Two main types of radiation therapy are available for prostate cancer treatment, including internal radiation (brachytherapy) and external beam radiation therapy (EBRT). For stage 3 disease, radiation therapy is used in one or two ways, 1) a single therapy, 2) part of a combination treatment with other treatment methods. Combination therapy involving hormone therapy and radiation therapy is a standard combination therapy for stage 3 prostate cancer.

  • Chemotherapy – anti-cancer drugs can be used to kill prostate cancer cells. These drugs block the way cancer cells grow and multiple anywhere in the body. Common drugs used for advanced prostate cancer included Docetaxel and Cabazitaxel. They are sometimes combined with hormone therapy to improve treatment outcomes.

Which treatments are suitable for me?

The best treatment for advanced prostate cancer depends on many things, including age, overall health, treatment response, and previous treatments. Surgery reduces disease-specific mortality, risk of disease progression, and metastasis (Bill-Axelson et al., 2005). 

For ADT, prostate cancer cells may become insensitive to the levels of androgen in the body, leading to treatment resistance. At the same time, there is evidence that stage T3a or lower, with less than 8 Gleason score and PSA lower than 20 ng/ml, benefit most from surgical therapy (Mongiat-Artus et al., 2009; Palisaar and Noldus, 2008).

In a comparative study, Gibert et al. demonstrated that surgery and radiation therapy have a comparable level of disease-specific mortality and risk of disease progression (Giberti et al., 2009).

Treatment side effects

These treatments can cause side effects, including:

Treatment to manage disease and treatment symptoms

Stage 3 prostate cancer cause symptoms, such as urinary incontinence and pain. Treatments can worsen these symptoms. You may one or more the following treatments to manage these symptoms:

  • Pain-relieving drugs 

  • Radiotherapy – radiotherapy can be used to relieve symptoms after or before treatment with other methods. 

Other treatment options for stage 3 prostate cancer 

As individual factors may affect the suitability of these treatment options, a doctor may recommend watchful waiting or active surveillance. Suitability is particularly important to avoid treatment side effects in some groups of men. 

  • Watchful waiting – for older men or those with other terminal illnesses where treatments side effects will affect their quality of life, doctors may recommend watchful waiting. Here, the doctor monitors the prostate cancer for evidence of disease progression before administering treatment.

  • Active surveillance – in addition to monitoring, the doctor may administer routine screening. Monitoring disease activity allows doctors to balance the risk of disease progression against the need to avoid unnecessary treatment.

Conclusion

Stage 3 prostate cancer is locally advanced disease, with an increased risk of progression in the absence of treatment. Men with specific characteristics, including older men, black men, and those with a family history of prostate cancer have an increased risk of prostate cancer.

These factors also increase the risk of disease progression. Prostate cancer can progress to locally advanced cancer (Stage III), affecting nearby tissues. Stage III prostate cancer causes significant genito-urinary complications and reduces men’s quality of life. 

There is no single reliable way to treat locally advanced prostate cancer. One or more hormone therapy, radical prostatectomy, radiation therapy, and chemotherapy are routine treatment options.

However, side effects and the risk of relapse remain a significant concern. The progress in cancer diagnosis and the treatment of prostate cancer has resulted from extensive clinical trials. There are several areas of active research to develop better methods to treat stage 3 prostate cancer. Speak to your medical provider about participating in trials evaluating such treatment options.

Sources

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  2. Bill-Axelson, A., Holmberg, L., Ruutu, M., Häggman, M., Andersson, S.-O., Bratell, S.,
  3. Spångberg, A., Busch, C., Nordling, S., Garmo, H., 2005. Radical prostatectomy versus watchful waiting in early prostate cancer. N. Engl. J. Med. 352, 1977–1984.
  4. Crawford, E.D., 2003. Epidemiology of prostate cancer. Urology 62, 3–12.
  5. Ferlay, J., Shin, H., Bray, F., Forman, D., Mathers, C., Parkin, D.M., 2010. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 127, 2893–2917.
  6. Ferris-i-Tortajada, J., Garcia-i-Castell, J., Berbel-Tornero, O., Ortega-Garcia, J., 2011 Constitutional risk factors in prostate cancer. Actas Urol. Esp. Engl. Ed. 35, 282–288.
  7. Giberti, C., Chiono, L., Gallo, F., Schenone, M., Gastaldi, E., 2009. Radical retropubic prostatectomy versus brachytherapy for low-risk prostatic cancer: a prospective study. World J. Urol. 27, 607–612.
  8. Hatcher, D., Garrett Daniels, I.O., Lee, P., 2009. Molecular mechanisms involving prostate cancer racial disparity. Am. J. Transl. Res. 1, 235.
  9. Mongiat-Artus, P., Peyromaure, M., Richaud, P., Droz, J., Rainfray, M., Jeandel, C., Rebillard,
  10. X., Moreau, J., Davin, J., Salomon, L., 2009. Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French
    association of urology. Progres En Urol. J. Assoc. Francaise Urol. Soc. Francaise Urol. 19, 810–817.
  11. Palisaar, R., Noldus, J., 2008. The role of surgery in locally advanced prostate cancer. Urol. Ausg A 47, 1417–1423.

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