Overview
Prostate cancer is referred to as stage II when the cancer can be detected by a digital rectal examination (DRE) or an elevated prostate-specific antigen (PSA), and there is no evidence that the cancer has spread outside the prostate to other organs. Stage II disease may also be further divided into the following depending on how much tissue is involved in the tumor (cancer):
- T2a: The cancer involves half or less of a lobe (section) of the prostate.
- T2b: The cancer involves half or more of a lobe of the prostate, but the other section isn’t involved at all.
- T2c: The cancer involves both lobes of the prostate.
Should All Patients Receive Treatment of Stage II Prostate Cancer?
If prostate cancer is truly confined to the prostate, it is curable with surgery or radiation. However, in order to benefit from curative treatment, a patient’s life expectancy may need to be 10-20 years from the time of prostate cancer diagnosis. This is because many prostate cancers are slow growing and men will sometimes die from other causes before they succumb to prostate cancer. Individuals may ask themselves: If cure is possible, is it necessary? Treatment of prostate cancer is a very personal decision; the choice of radiation versus prostatectomy is often based on weighing the possible complications of treatment and the relative inconvenience of the treatments. It is important to be seen by more than one physician to determine the likely treatment outcome associated with the various options available in your community. Before deciding on receiving treatment, patients should ensure they understand the answers to 3 questions:
- What is my life expectancy and risk of cancer progression without treatment?
- How will my prognosis be improved with treatment?
- What are the risks or side effects of the various treatment options?
Primary Treatment Options for Stage II Prostate Cancer
Patients with stage II prostate cancer are curable and have a number of treatment options, including surgical removal of the cancer with radical prostatectomy, radiation therapy with brachytherapy or External Beam Radiation (EBRT) or active surveillance without immediate treatment. 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.
Before making treatment recommendations, physicians who treat prostate cancer consider a number of aspects about the patient’s health, life expectancy and the cancers risk of progression that help predict whether the cancer is truly confined to the prostate and how fast the cancer will grow. These include the clinical stage of the cancer, the prostate-specific antigen (PSA) level, and the appearance of the prostate cancer cells under the microscope (the Gleason score). Together they can be used to predict an individual’s risk of prostate cancer recurrence.
- Low risk: PSA <10 ng/mL, Gleason score < 6 and clinical stage T1c or T2a
- Intermediate risk: PSA >10 to 20 ng/mL or Gleason score of 7 or clinical stage T2b
- High risk: PSA >20 ng/mL or a Gleason score of 8 to 10 or clinical stage T2c
In general, for patients with low or intermediate risk, early stage prostate cancer, treatment with radical prostatectomy, EBRT or brachytherapy appears to produce equivalent outcomes but these treatments are associated with different side effects. In patients with higher risk disease, however, treatment with EBRT or radical prostatectomy appears to produce superior results compared to brachytherapy however there is a significant risk of cancer recurrence and additional treatment strategies are being developed to improve outcomes.1, 2
Radical Prostatectomy: Radical prostatectomy involves surgical removal of the prostate gland and a small amount of surrounding normal tissue. Surgical removal of the prostate is a very effective therapy if the cancer has not spread beyond the prostate and is a standard treatment for individuals with low, intermediate, and high-risk stage II cancer. Over 90% of patients with low-risk, and over 75% of those with intermediate risk prostate cancer treated with radical prostatectomy will survive greater than 10 years after surgery alone.1, 3 Learn more about radical prostatectomy and its side effects.
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 (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.
Because radiation implants focus the radiation closely around the prostate, this form of radiation works best in patients with low or intermediate risk stage II prostate cancer. For high-risk patients another form of treatment may be better suited for the patient. In addition, patients with a large prostate gland, prior history of prostate infections or recent transurethral resection of the prostate (TURP) may not be able to undergo the implantation procedure for brachytherapy.1, 4, 5 Learn more about the risks and benefits of EBRT and brachytherapy.
Active Surveillance: Some physicians and patients choose a strategy of delaying any treatment of prostate cancer until symptoms from the cancer appear. Because treatment with radiation or surgery may be associated with side effects, in addition to inconvenience, electing not to receive immediate treatment may be appropriate for selected patients especially those with other health concerns or a shorter life expectancy. This strategy may be described as “watchful waiting” or “active surveillance”
Watchful waiting is based on the premise that some patients will not benefit from definitive treatment of the primary prostate cancer. The decision is to forgo definitive treatment and to instead provide treatment to relieve symptoms of local or metastatic progression if and when it occurs. In contrast to watchful waiting, a program of active surveillance is based on the premise that some, but not all, patients may benefit from treatment of their primary prostate cancer. A program of active surveillance is designed to provide definitive treatment for men with localized cancers that are likely to progress and to reduce the risk of treatment-related complications for men with cancers that are not likely to progress. Clinical studies suggest that individuals with lower risk cancers could be candidates for this treatment strategy because they have a low risk for clinical progression of their cancer within the first 10 to 15 years after the diagnosis. Thus this treatment strategy may be best suited for men with a shorter life expectancy.3, 6, 7
Treatment of the High-Risk Stage II Prostate Cancer
Although active surveillance, brachytherapy, EBRT, and radical prostatectomy are options for the management of patients with high-risk stage II prostate cancer, recurrence rates are high. There are several areas of ongoing research where doctors are evaluating new treatment approaches to reduce the risk of cancer progression and improve survival of individuals with high-risk prostate cancer.
The current standard treatment for high-risk stage II prostate cancer is EBRT in conjunction with long-term androgen deprivation therapy (ADT). By combining ADT with a higher dose of EBRT delivered with 3D-CRT or IMRT radiation therapy the outcomes of high-risk patients can be improved. Generally, high-risk patients are usually not considered for treatment with brachytherapy; however, certain clinical scenarios may warrant the use of brachytherapy boost in combination with EBRT. Additionally, radical prostatectomy may be considered for selected high-risk-patients, although, it is a seemingly less popular approach due to the invasive nature in comparison to EBRT as well as the distinct set of complications which surgery poses; including perioperative mortality, long-term sexual dysfunction, and urinary incontinence. Additionally, the high likelihood that postoperative radiotherapy will be required potentially exposes patients to toxicities of both surgery and radiotherapy.1, 3, 8
Radiation After Prostatectomy
A significant number of patients will still require postoperative radiation following radical prostatectomy because they are at an increased risk of cancer recurrence. Clinical studies have demonstrated that adjuvant radiation following radical prostatectomy may prolong the time until PSA recurrence, delay the use of hormonal therapy, and improve overall survival for certain patients.
Adjuvant radiation therapy is typically offered to high-risk patients following surgical prostatectomy. This includes individuals defined as high-risk and those found to have cancer involving the margins of the surgical specimen, seminal vesicle invasion, positive surgical margins, or extraprostatic extension following prostatectomy and individuals where the PSA remains persistently elevated.
The ideal time to deliver radiation therapy following radical prostatectomy is the subject of some debate. Radiation can be administered immediately after prostatectomy to high-risk individuals or in some cases delayed until there is evidence of PSA recurrence. The understanding of how best to use radiation following prostatectomy continues to evolve and patients should discuss the role and timing of radiation with their treating physician.9
Androgen Deprivation Therapy
In the management of high-risk prostate cancer ADT has been used before (neoadjuvant), during (concurrent), and after (adjuvant) local therapy. Hormone therapy deprives a man’s body of male hormones necessary for prostate cancer to grow. Clinical studies have demonstrated that ADT combined with EBRT delays cancer progression and improves survival in men with high-risk prostate cancer. The use of hormone therapy to shrink the prostate cancer prior to radical prostatectomy or radiation therapy can be used to 1) to reduce the prostate size prior to prostate brachytherapy and 2) to sensitize malignant cells to radiation during EBRT. Hormonal therapy prior to radiation therapy results in an average 20% shrinkage of prostate volume. This volume reduction may reduce the number of prostate cancer cells and diminish the volume irradiated decreasing the side effects. The understanding of how best to use ADT in men with high-risk prostate cancer continues to evolve and patients should discuss the role of ADT carefully with their treating physician.3, 5
Strategies to Improve Treatment
The progress that has been made in the treatment of prostate cancer has resulted from development of better treatments that were evaluated in clinical studies. Future progress in the treatment of stage II prostate cancer will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of localized prostate cancer.
Timing of Radiation: Although the use of radiation following prostatectomy improves outcomes in high-risk patients, some patients do not benefit and are exposed to its side effects unnecessarily. Clinical trials are ongoing to determine which patients benefit from radiation and whether radiation is best used immediately following prostatectomy or can be delayed in selected patients.
Newer Radiation Machines: Most EBRT uses high energy x-rays to kill cancer cells. Some radiation oncology centers use different types of radiation that 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.10, 11
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 dose 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.8
Androgen Deprivation Therapy: Although Clinical studies have demonstrated that ADT combined with EBRT delays cancer progression and improves survival in men with high-risk prostate cancer, the optimal timing and duration of ADT is still being evaluated in clinical trials as is the role of ADT following prostatectomy in high risk patients.
Systemic Treatment of High Risk Patients: There is some evidence to suggest that the use of other systemic treatments like chemotherapy, which may be used alone or in combination with ADT may be beneficial in selected high-risk patients following local treatment with prostatectomy or EBRT. Clinical trials are ongoing to evaluate its potential benefits.
References
1 http://www.auanet.org/education/guidelines/prostate-cancer.cfm
2 Albertsen, P. C., Hanley, J. A., Barrows, G. H., Penson, D. F., Kowalczyk, P. D., Sanders, M. M. et al: Prostate cancer and the Will Rogers phenomenon. J Natl Cancer Inst, 97: 1248, 20053
3 Bill-Axelson, A., Holmberg, L., Ruutu, M., Haggman, M., Andersson, S. O., Bratell, S. et al: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med, 352: 1977, 2005
4 Sylvester, J. E., Blasko, J. C., Grimm, P. D., Meier, R. and Malmgren, J. A.: Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: the Seattle experience. Int J Radiat Oncol Biol Phys, 57: 944, 2003
5 D’Amico, A. V., Manola, J., Loffredo, M., Renshaw, A. A., DelaCroce, A. and Kantoff, P. W.: 6-Month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA, 292: 821, 2004
6 Klotz, L.: Active surveillance with selective delayed intervention for favorable risk prostate cancer. Urol Oncol, 24: 46, 2006
7 Adolfsson, J., Oksanen, H., Salo, J. O. and Steineck, G.: Localized prostate cancer and 30 years of follow-up in a population-based setting. Prostate Cancer Prostatic Dis, 3: 37, 2000
8 Bolla, M., Collette, L., Blank, L., Warde, P., Dubois, J. B., Mirimanoff, R. O. et al: Long- term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet, 360: 103, 2002
9 Wiegel T, Bottke K, Steiner U et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. Journal of Clinical Oncology. 2009;27:2924-30.
10 Zietman AL, Bae K, Slater J, et al. Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: Long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09. Journal of Clinical Oncology. 2010; 28: 1106-1111.
11 Yu JB, Soulos PR, Herrin J, et al. Proton versus intensity-modulated radiotherapy for prostate cancer: Patterns of care and early toxicity. Journal of the National Cancer Institute. Published early online December 14, 2012. doi: 10.1093/jnci/djs463