乌鸦传媒

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Although prostate cancer is the most common cancer affecting men in the United States, with an estimated diagnosed each year, the majority of men with prostate cancer can live for many years and not die of the disease. Having a detailed, thorough evaluation of the individual patient's cancer-based prognosis, as well as non-cancer-related life expectancy is critical to determining which of the many treatment options are best.

The standard treatments for stages I–III prostate cancer are active surveillance, prostatectomy, and radiotherapy. Patients whose cancer has spread outside the prostate gland may receive systemic therapies, including hormone therapy, chemotherapy, immunotherapy, or targeted therapy. For small localized tumors within the prostate, focal therapy, such as high-intensity focused ultrasound, cryotherapy, laser ablation, or photodynamic therapy, may be considered.

For early-stage prostate cancers, physicians typically use risk groups to help determine if more tests should be done and to help guide treatment options. "Additional tests are done for patients if there is considered to be a risk that the cancer has spread outside the prostate. Research has shown that patients with very low-risk disease based on prostate-specific antigen [PSA] level and pathology have a very small chance of having cancer that has spread to distant sites," said William Dahut, MD, chief scientific officer for the American Cancer Society.

When looking at treatment decisions, physicians first examine the expected volume and the potential biology of the disease. This is determined by the PSA value, imaging studies, and the pathology of the tumor. Most patients have multiple treatment decisions to make once this information is available. The final decision is usually made based on the patient's age, personal preferences, other medical problems, and sometimes the availability of clinical trials, said Dahut.

When considering surgery or radiation, the primary tools for treating localized disease, functional age becomes a factor, since older men tend to become less physically fit. Physicians also need to consider other ongoing medical issues, such as coronary artery disease and history of stroke or myocardial infarction.

Certain medications may increase the risk of other medical conditions or be contraindications. For example, the anti-androgen abiraterone may not be appropriate for patients with kidney or liver dysfunction. The nonsteroidal antiandrogens enzalutamide and apalutamide raise concerns about cognitive impairment and balance, particularly in elderly patients.

Common Procedures

is the most common surgical technique for prostate cancer. Radical prostatectomy is usually reserved for patients with stage I and II disease who are in good health and have an estimated life expectancy of at least 10 years.

Radiation therapy may be a good option for patients who are considered non-optimal medical candidates for radical prostatectomy. The two types of radiation therapy commonly used are , which includes that directs high doses of radiation toward the tumor while sparing healthy tissue; and , which involves placing radioactive seeds inside the prostate. Patients undergoing brachytherapy often have a low Gleason score, low PSA level, and stage T1 to T2 tumors.

that use freezing, heat, or electricity are under investigation and have a potential future role for patients as tumor prognosis and imaging improves over time, Dahut noted. These are also used for patients who have recurrent cancer after radiation. To date, however, has not been shown to have better overall outcomes than other techniques used to deliver radiation for prostate cancer, he added.

Classifying Prostate Cancer

Prostate cancer is classified differently from other cancers. "Unlike other numerical staging systems based on how the cancer is distributed throughout the body, we consider prostate disease as more 'evolutionary,' because patients often live with it for many years," explained Andrew Laccetti, MD, of Memorial Sloan Kettering Cancer Center in New York City. The distribution of disease, whether it is localized or metastatic, and is androgen sensitive or insensitive all become part of the mix in the treatment plan.

Patients with very low-risk disease, and low-risk disease in general, should be offered active surveillance.

Patients with intermediate-risk disease can be offered surgery or radiation and possibly active surveillance in well-selected patients with favorable risk features. Radiation is sometimes also given along with a short course of hormonal therapy.

In high-risk and very high-risk patients, surgery may still be an option, but patients may often need radiation therapy after the completion of surgery. Radiation therapy in this population is usually given with prolonged hormonal therapy, often for 18-24 months.

The Value of Assessing PSA

After surgery or radiation therapy, monitoring PSA levels adds value to continued treatment, Laccetti noted. For most patients, PSA testing is the most sensitive way to detect early prostate cancer recurrence. Following surgery or curative-intent radiation, the primary use of PSA testing is to survey patients for relapses. "It's like a canary in a coal mine -- we can see subtle changes in PSA earlier than evidence of cancer on a CT scan," he said.

A study of 8,669 prostate cancer patients found that a short post-treatment PSA doubling time of less than 3 months fulfills some criteria as a for all-cause mortality and prostate cancer-specific mortality after surgery or radiation therapy. A PSA value after surgery should be undetectable, Dahut said. In patients who have had radiation, PSA is still detectable. Ideally PSA values should be lower than 1 ng/mL and even lower than that -- potentially 0.5 ng/mL.

After can help predict clinical outcomes and survival. But androgen-deprivation therapy can decrease serum PSA levels independent of tumor response, so PSA levels alone cannot be relied upon to monitor a patient's response to hormonal therapy, and clinical factors need to be taken into account.

Several are associated with prostate cancer outcomes, including markers of apoptosis including Bcl-2 and Bax; markers of proliferation rate, such as Ki67; TP53 mutation or expression; p27; E-cadherin; microvessel density; DNA ploidy; p16; and PTEN gene hypermethylation and allelic losses. None of these, however, have to date become part of the routine management of patients because they have not been prospectively validated.

Shared Decision-Making

Physicians play an important role in helping patients consider the most appropriate treatment options. This should be a shared decision-making process, with a detailed discussion of available treatments, their pros and cons, and the anticipated treatment schedule to find the best therapy.

"Each man needs to understand the risk that his prostate cancer will cause him, including morbidity and potentially mortality. He needs to look at his overall health and ultimately the need to weigh the potential immediate side effects of treatment versus the potential of delaying or eliminating later morbidity from cancer," Dahut said. He suggests that patients talk to multiple physicians before making a decision, particularly physicians skilled in both radiation and surgery.

Most of the time initial prostate cancer care is led by a urologist and radiation oncologist. Medical oncologists tend to become involved in cases where there is a greater risk of biologically more aggressive disease or in patients with metastatic disease. "The oncologist should be able to explain the individual risks, as well as the need for additional tests, such as genetic testing, in patients who have high-risk features," Dahut said.

are very important, particularly in those patients whose prostate cancer is biologically more aggressive, he added. "A trained oncologist should be sure to present trial options in those patients with prostate cancer that is considered high-risk or metastatic."

Read previous installments in this series:

Part 1: Prostate Cancer: Epidemiology, Diagnosis, and Treatment

Part 2: The Latest on Prostate Cancer Diagnosis

Part 3: The Real-Life Consequences of Controversies About PSA Testing

Part 4: Case Study: What Is Causing This Painful Abdominal Mass and Systemic Symptoms?