Overview

Prostate cancer is referred to as stage III if the cancer can be detected by digital rectal examination and has extended through the capsule that encloses the prostate gland and may involve nearby tissues. Stage III prostate cancer is further divided into the following categories, depending on how extensive the cancer is:

  • T3a: The tumor has extended outside of the prostate on one side.
  • T3b: The tumor has extended outside of the prostate on both sides.
  • T3c: The tumor has invaded one or both of the seminal vesicles, which are small bag-like organs near the bladder.

Patients with stage III disease do not have detectable cancer in the lymph nodes or other distant areas of the body.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage III prostate cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Prostate cancer is typically a disease of aging. It may persist undetected for many years without causing symptoms. While most men with stage I-II prostate cancer die from causes other than cancer, men with locally advanced or stage III cancer are more likely to die from prostate cancer rather than with prostate cancer. Some patients with stage III prostate cancer are curable and have, historically, been treated with either surgery or radiation therapy. Given the poor results of single treatment approaches, it is increasingly common to use one or more treatment strategies in combination. It is important for patients to obtain as much information as possible about the results of each treatment modality and to obtain more than one opinion on the matter, especially when deciding on surgery versus radiation therapy.

Should All Patients Receive Aggressive Treatment of Prostate Cancer?

Patients diagnosed with locally advanced prostate cancer must choose between treatment with radiation therapy, surgery (radical prostatectomy), participation in a clinical study or “watchful waiting” in selected circumstances. Unfortunately, well-controlled clinical studies comparing these treatment approaches have not been performed. Before deciding on receiving treatment, patients should ensure they understand the answer to 3 questions:

  • What is my life expectancy and risk of cancer recurrence without treatment?
  • How will my prognosis be improved with treatment?
  • What are the risks of the various treatment alternatives?

Patients with stage C or “locally advanced” prostate cancer do not have any clinical evidence of cancer involving the pelvic lymph nodes. This would suggest that the cancer is confined to the prostate and could be effectively treated with local therapy (surgery or radiation). If prostate cancer is truly confined to the prostate, it is curable with surgery and/or radiation. Unfortunately, 20-50% of patients undergoing radical prostatectomy will be found to have cancer involving the pelvic lymph nodes at the time of surgery. For these patients, the risks and side effects of surgery will have been unnecessary because the surgery cannot cure the cancer.

Before making treatment recommendations, physicians who treat prostate cancer consider a number of aspects about the patient’s disease that help predict whether the cancer is confined to the prostate (potentially curative) and how fast the cancer will grow. These aspects include the clinical stage of the disease, the prostate-specific antigen (PSA) level, and the appearance of the prostate cancer cells under the microscope (the Gleason score).

Patients most likely to benefit from aggressive surgical treatment can initially undergo a simple procedure called a pelvic lymph node dissection. If the lymph node dissection indicates that lymph nodes are involved, the patient can be spared surgery.

Radiation Therapy

Radiation therapy is treatment with high energy x-rays that have the ability to kill cancer cells. Standard radiation therapy utilizes either external beam radiation therapy (EBRT) consisting of daily treatments on an outpatient basis for approximately 6 to 8 weeks or interstitial brachytherapy which involves permanent placement of radioactive seeds directly into the prostate gland. Radioactive implants are increasingly being used instead of radical prostatectomy or EBRT.

The actual area of the pelvis receiving radiation treatment may be large or focused only on the prostate. Because patients with stage III prostate cancer often have undetected cancer cells in the pelvic lymph nodes, radiation therapy may be directed to the lymph nodes in the pelvis, in addition to the prostate gland. If patients begin needing treatment to a larger area of the pelvis, they may undergo another planning session to focus the radiation to the prostate gland, where cancer cells are greatest.

Because radioactive implants focus the radiation closely around the prostate, this form of radiation does not work as well in patients with stage III prostate cancer unless combined with EBRT. The purpose of the EBRT is to treat the surrounding tissues and lymph nodes where cancer cells may have spread. The radioactive implant seeds deliver an increased radiation dose to the prostate where the cancer cells are greatest. The combination of internal and external radiation may permit high doses of radiation to be delivered to the cancer while minimizing side effects to surrounding organs.

Despite the prostate cancer being treated with radiation, over half of patients with stage III prostate cancer will experience recurrence of their cancer. This is because some patients already have small amounts of cancer that have spread outside the prostate that were not treated by radiation. Undetectable areas of cancer outside the prostate gland are referred to as micrometastases. It is the presence of micrometastases that may cause the relapses that follow treatment with radiation alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve the cure rate achieved with surgical removal of the cancer. Efforts are currently underway to find such a therapy.

Combined Modality Therapy

Approximately 60% of patients with stage III prostate cancer survive 5 years without evidence of prostate cancer after treatment with radiation therapy . Despite the prostate cancer being treated with radiation, many patients with stage III prostate cancer will experience recurrence of their cancer. Research indicates that multi-modality treatment, which combines chemotherapy, surgery, radiation, and hormonal therapy into a single treatment strategy improves cure and survival rates.

Several clinical studies have directly compared radiation therapy alone to a combination of radiation therapy and hormone therapy for locally advanced prostate cancer. Hormone therapy deprives a man’s body of male hormones necessary for prostate cancer to grow. Hormone therapy can affect the growth of prostate cancer everywhere in the body, whether the cancer cells are in the prostate itself or elsewhere in the body. The results of a study conducted in Europe that involved 401 patients showed a 50% increase in survival 5 years after treatment when hormone therapy was added to EBRT for three years.

In order to further evaluate whether combination therapy could be beneficial in the treatment of prostate cancer involving pelvic lymph nodes, a clinical study compared radiation therapy followed by adjuvant hormonal therapy to radiation therapy followed by delayed hormonal therapy initiated only at the time of cancer progression. Patients treated with radiation therapy and adjuvant hormonal therapy were more likely to be alive 5 years from initiation of treatment without evidence of cancer progression or development of distant metastatic disease than patients treated with radiation and delayed hormonal therapy. Both treatments, however, produced a similar chance of survival 5 years from treatment. The results of this clinical study suggest that the combination of radiation therapy and hormonal therapy reduces the time to cancer recurrence, and development of metastatic disease, and may improve a patient’s quality of life. The combination of radiation and adjuvant hormonal therapy improved the survival of some patients.

Delivery of hormonal therapy or chemotherapy prior to radiation treatment (neoadjuvant therapy) may be a more promising way to combine these treatment approaches. The Radiation Therapy Oncology Group (RTOG) conducted a clinical trial involving 1,323 men with localized prostate cancer whose risk of lymph node involvement was greater than 15%. The patients were randomly assigned to four treatment groups: whole-pelvic radiation therapy (WPRT) with neoadjuvant hormone therapy, WPRT with adjuvant hormone therapy (treatment following primary therapy), prostate-only radiation with neoadjuvant hormone therapy and prostate-only radiation with adjuvant hormone therapy. The purpose of this study was to determine which treatment combination was most effective at improving cancer progression-free survival.

Overall, patients who were treated with the combination of neoadjuvant hormonal therapy plus WPRT achieved superior results over the other treatment regimens. Four years following treatment, the cancer-free survival rates for the different therapies were 61% for neoadjuvant/WPRT, 49% for adjuvant/WPRT, 47% for adjuvant/prostate-only radiation and 45% neoadjuvant/prostate-only radiation.

Radical Prostatectomy

The majority of men with locally advanced prostate cancer are not candidates for surgery because the cancer is likely to have spread beyond the prostate. This is especially true for men with high Gleason scores or PSA levels. Men with low Gleason scores or low PSA levels have a greater chance of having organ-confined prostate cancer. Before a prostatectomy is performed, patients may want to have pelvic lymph nodes removed to see if they contain cancer. This is called a pelvic lymph node dissection. If the lymph nodes contain cancer, usually the surgeon will not proceed with a radical prostatectomy. Another form of treatment, usually hormone therapy, radiation therapy or participation in a clinical study is generally recommended.

Patients without evidence of lymph node invasion may want to proceed to radical prostatectomy. Approximately 80% of patients with surgically confined stage III prostate cancer (cancer confined to the prostate that can be surgically removed) will be alive 5 years after surgery, and most patients who die do so of causes other than prostate cancer. Depending on the features of the cancer, approximately 60% of patients will be without evidence of prostate cancer. Despite undergoing surgical removal of all detectable prostate cancer, many patients with stage III prostate cancer will experience recurrence of their cancer. It is important to realize that some patients with stage III disease already have small amounts of cancer that have spread outside the prostate and were not removed by surgery. Undetectable areas of cancer outside the prostate gland are referred to as micrometastases. The presence of micrometastases may cause the relapses that follow treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve the cure rate achieved with surgical removal of the cancer. Efforts are currently underway to find such a therapy.

“Watchful Waiting” or Conservative Management

Some physicians and patients choose a strategy of “watchful waiting” or “conservative management” of prostate cancer. Because treatment with radiation or surgery may be associated with temporary (and some permanent) side effects in addition to inconvenience, electing not to receive treatment may be appropriate for selected patients. Elderly patients and/or those with other significant medical problems may experience greater side effects from treatment and are more likely to die from causes other than prostate cancer. Thus, although many patients may require hormonal therapy or radiation therapy for palliation once their disease progresses, radical prostatectomy may not be beneficial for men with a life expectancy shorter than one decade.

“Watchful waiting” requires close follow-up of the cancer, and therapy is only initiated when the cancer shows signs of having spread. At this point, the treatment is typically hormonal. There is still much controversy over the optimal time to start hormonal therapy, i.e., is it better to treat early or to wait until there is progression of disease. Asking your physician to explain your chance of survival without treatment and the risk of cancer having spread beyond the prostate capsule will help you make your decision.

Strategies to Improve Treatment

The progress that has been made in the treatment of prostate cancer has resulted from improved development of radiation treatments and surgical techniques. Despite improvements in treatment, patients still succumb to the complications of prostate cancer. Surgery and radiation are local therapies directed at treating cancer in and around the prostate gland. Future progress in the treatment of prostate cancer will result from continued participation in appropriate clinical studies designed to improve local and systemic treatment of prostate cancer. Currently, there are several areas of active exploration aimed at improving the treatment of stage III prostate cancer.

Strategies to improve systemic therapy: Surgery and radiation are local therapies directed at treating cancer in and around the prostate gland. Treatment administered before local therapy is called neoadjuvant therapy. Administering systemic therapies, such as hormonal therapy and chemotherapy, before local therapy is a strategy that is being actively investigated. This technique can shrink the cancer so that it is more treatable with local therapies.  Over the past several years, many new anti-cancer drugs have been discovered that are more active at destroying cancer cells. Administration of these newer anti-cancer agents in addition to radiation or surgical removal of prostate cancer may improve the treatment of locally advanced prostate cancer.

Neoadjuvant hormone therapy: Hormone therapy deprives a man’s body of male hormones necessary for prostate cancer to grow. The use of hormone therapy to shrink the prostate cancer prior to radical prostatectomy or radiation therapy is being evaluated for patients with prostate cancer. Some urologists are trying to make radical prostatectomy more successful for stage III prostate cancer by shrinking the cancer prior to surgery with hormone therapy. Hormonal therapy prior to local treatment appears to decrease the size of the prostate cancer by approximately 20-50%. The use of neoadjuvant hormone therapy prior to radical prostatectomy is being evaluated in clinical studies.

Neoadjuvant chemotherapy: Administration of chemotherapy before either surgery or radiation, called neoadjuvant chemotherapy, can shrink the cancer so that it is more treatable with local therapies. Chemotherapy also provides the benefit of killing cancer cells that have already spread away from the prostate and are not treated with local radiation or hormonal therapy. Cancer cells that have spread are thought to be the most likely cause of cancer recurrence or relapse after local therapy.

Taxotere and estramustine are among the most active drug regimens for the treatment of prostate cancer. Neoadjuvant Taxotere/estramustine appears to be an active treatment for patients with locally advanced prostate cancer that are considered to be at a high risk of experiencing a cancer recurrence. When the combination of Taxotere/estramustine was administered prior to either surgery or radiation therapy in the treatment of 21 patients, more than half of the patients had no detectable cancer after the neoadjuvant chemotherapy. Another 48% experienced a partial anti cancer response to treatment. Approximately 13 months following therapy, 71% patients had remained cancer free.[1]

Combination chemotherapy and hormone therapy: Research indicates that combination chemotherapy and hormone therapy may improve survival in patients with locall advanced prostate cancer. Recently, researchers in England conducted a clinical trial evaluating treatment consisting of hormone therapy plus the chemotherapy agent mitozantrone versus hormone therapy alone for patients with locally advanced prostate cancer. Hormone therapy in this trial consisted of injections of an agent that reduced the production of androgens (particularly testosterone) in the body. Ninety-five percent of patients who received the combination treatment experienced a complete or partial disappearance of their cancer, compared to only 53% of patients who received only hormone therapy. Importantly, the average duration of survival following therapy was significantly higher in patients who received both mitozantrone and hormone therapy, nearly 7.5 years, compared to 3 years for patients receiving only hormone therapy.

Advances in local treatment: Several strategies to improve local treatment of prostate cancer are under evaluation. All of these strategies either increase the dose of radiation delivered to the cancer or expand the field of radiation. They only treat cancer confined to the prostate and do not treat cancer cells beyond the radiation or surgical field.

Simultaneous radiation therapy: Simultaneous radiation therapy employs permanent interstitial prostate brachytherapy with seed followed by EBRT. The patient receives therapeutic doses of radiation from both the implant and the external beam. The timing of this combination of modalities is distinct from that of other combinations of EBRT and brachytherapy used for prostate cancer.

Combination radiation therapy: Some radiation oncologists are combining EBRT and interstitial seed brachytherapy for patients with stage II or III cancers. The purpose of the EBRT is to treat the tissues surrounding the prostate gland and lymph nodes where cancer cells may have spread. The interstitial seeds serve to deliver extra radiation doses to the prostate where the cancer cells are greatest. The combination of internal and external radiation is being evaluated to allow higher doses of radiation to the cancer while minimizing side effects to surrounding organs.

Researchers recently evaluated the effectiveness of brachytherapy plus EBRT versus EBRT alone in the treatment of over 300 patients with advanced localized prostate cancer. Half of the patients received treatment consisting of both brachytherapy and EBRT and the other half received EBRT alone. Five years following treatment, high PSA levels existed in only 33% of patients that had received the combination of brachytherapy plus EBRT compared to 56% of patients that received EBRT alone. Since high PSA levels are an indication of the presence of cancer, these results suggest that brachytherapy plus EBRT may be more effective than EBRT alone in the treatment of advanced localized prostate cancer.

Whole pelvic radiation therapy: Because certain patients are at higher risk of cancer involving the pelvic lymph nodes, some doctors have advocated expanding the radiation field to include the pelvic lymph nodes. This is referred to as whole pelvic radiation therapy (WPRT). Some, but not all, comparisons of WPRT to prostate only radiation therapy have demonstrated that WPRT may improve survival and is not more toxic than radiation to the prostate only. Many doctors believe, however, that if cancer has spread to the pelvic lymph nodes, it has probably spread elsewhere in the body and expanding the radiation field will be of little benefit. Efforts to improve treatment might be better focused on systemic treatment approaches versus local treatment with radiation. Doctors in the United States are currently conducting a clinical study comparing WPRT to prostate only radiation.

Newer radiation techniques: EBRT can be delivered more precisely to the prostate gland by using a special CT scan and targeting computer. Efforts to improve the cure rate of prostate cancer with radiation therapy are under investigation. One exciting technique is the use of three-dimensional (3D) computer targeting systems to precisely aim the radiation beam at the prostate gland. This 3D conformal radiation therapy technique appears to reduce side effects to the surrounding organs, thereby allowing higher radiation doses. Clinical studies using 10-20% higher radiation doses to the prostate cancer with 3D radiation therapy are underway.

Newer radiation machines: Most EBRT uses high energy x-rays to kill cancer cells. Some radiation oncology centers use different types of radiation which require special machines to generate. These different types of radiation, such as protons or neutrons, appear to kill more cancer cells with the same dose. Combining protons or neutrons with conventional x-rays is one method of radiation therapy being evaluated in clinical trials.

References


[1] Hussain M, Smith D, El-Rayes B, et al. Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locally advanced prostate cancer. Urology. 2003;61:774-780.

Copyright ©; 2014 Omni Health Media Prostate Cancer Information Center. All Rights Reserved.