Diagnosis and treatment of prostate cancer: what is new?

Prostate cancer (PCa) is the most common solid organ malignancy among American men (1). The probability to develop PCa in a whole life between 2012 and 2014 in United States was 1 out of 9 and 29,430 is the estimated number of deaths for PCa in US during 2018. The scenario for diagnosis and treatment of prostate cancer has greatly changed in the last 10-5 years. So far, the use of prostate-specific antigen (PSA) and multiparametric magnetic resonance (followed by prostatic biopsies) represents the most accepted diagnostic pathway for Pca. In cancer care, different types of doctors - including medical oncologists, surgeons, and radiation oncologists - often work together to create an overall treatment plan that may combine different type of treatments to treat the cancer.

Diagnosis

Prostate cancer (PCa) is the most common solid organ malignancy among American men (1). The probability to develop PCa in a whole life between 2012 and 2014 in United States was 1 out of 9 and 29,430 is the estimated number of deaths for PCa in US during 20181. So far, the use of prostate-specific antigen (PSA) followed by random biopsies represents the most accepted diagnostic pathway for Pca (2).

The use of these screening methods is, nowadays, one of the most controversial topic in urology. Evidences regarding benefit originating from PCa PSA-based screening are contradictory (3,4). The most updated Cochrane review demonstrated that PCa screening did not significantly decrease prostate cancer-specific mortality up to 10 years (5). On the other hand, US Preventive Services Task Force recommendations against PSA screening (6), issued in 2012, was related with a subsequent increase in the incidence of high grade and locally advanced tumors (7). Results from two meta-analyses of subsequent randomized studies demonstrated that PSA screening leads to a small reduction in the risk of dying from prostate cancer over 10 years (8,9). Taken together, these findings led USPSTF to update its recommendation in 2018, now allowing men aged between 55 and 69 years old a choice to undergo PSA-based screening (10). This also led the European Association of Urology in supporting the use of PSA as a screening tool in 2019 (11)

The current gold-standard in PCa diagnosis, represented by 12-cores systematic random biopsy (TRUS-Bx)(12), is affected by several sampling errors which account for the most part of failure to detect clinically significant prostate cancer (csPCa), imprecise tumor risk stratification and detection of clinically insignificant PCa13 with a significant rate of false negative (14).

Even though during the last few decades there has been a rapid decline in PCa mortality (1), this seemed to be only in part related to the extensive use of PSA and random biopsies but also due to other factors as, for example, advances in therapeutic strategies (15).

Literature is concordant instead in stating that the widespread use of these diagnostic strategies has led to overdiagnosis (up to 45%) and overtreatment of low volume and indolent tumors (3,16).

With the aim to improve the diagnostic pathway of PCa, both providing early diagnosis of localized diseases and avoiding overdiagnosis of non-significant cancers, there has been growing interest in multiparametric magnetic resonance imaging of the prostate (mpMRI)(Figure 1). This imaging method was initially introduced in the 1980s with staging purposes (17) and has recently emerged as the most promising diagnostic modality which, compared to the other available tools, has the ability to directly assess the presence of areas likely to harbor significant cancer within the prostatic gland, defining the size, the location and the stage and lastly guiding a biopsy. In 2019, PSA and mpMRI are the best indicators to suspect the presence of a prostate cancer and guide to perform a prostate biopsy which remain the only tool to diagnose a prostate cancer.

Standardized MRI Reporting Scheme

Figure 1 : standardized MRI Reporting Scheme for mpMRI of the prostate

Treatment

In cancer care, different types of doctors—including medical oncologists, surgeons, and radiation oncologists—often work together to create an overall treatment plan that may combine different type of treatments to treat the cancer. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as palliative care experts, physician assistants, advanced nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, physical therapists, and others (18).

Descriptions of the most common treatment options for prostate cancer are reported below. Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patient’s preferences and overall health.

Early-stage prostate cancer (stages I and II). Early-stage prostate cancer usually grows very slowly and may take years to cause any symptoms or other health problems, if it ever does at all. As a result, active surveillance may be recommended. Radiation therapy (external-beam or brachytherapy) or surgery may also be suggested, as well as clinical trials. For men with a higher Gleason score, the cancer may be faster growing, so radical prostatectomy and radiation therapy are often appropriate.

ASCO, the American Urological Association, American Society of Radiation Oncology, and the Society of Urologic Oncology recommend that men with high-risk early-stage prostate cancer that has not spread to other areas of the body should receive radical prostatectomy or radiation therapy with androgen-deprivation therapy (ADT) as standard treatment options.

Men with locally advanced prostate cancer who choose not to have surgery should not have systemic therapy with either ADT or chemotherapy before surgery. Men with locally advanced prostate cancer who choose radiation therapy should receive ADT as the standard of care. ADT given for 24 months is widely accepted as the least amount of time needed to control the disease, but 18 months may also be enough. Adjuvant or salvage radiation therapy is treatment that is given after radical prostatectomy. It is a standard of care for men with extraprostatic extension, regardless of Gleason score and margin status (positive or negative). Having positive margins means that cancer cells were found in margins of the tissue removed during surgery that surrounded the prostate. Having positive margins does not necessarily mean that cancer was left behind during surgery. The role of adjuvant radiation therapy for men who have microscopic cancer in their lymph nodes is still being studied.

Prostate cancer treatments can cause side effects, such as erectile dysfunction, which is the inability to get and maintain an erection, and incontinence, which is the inability to control urine flow or bowel function. These treatments for prostate cancer may seriously affect a man’s quality of life. In addition, many prostate cancers grow slowly and cause no symptoms or problems. For this reason, many men may consider delaying cancer treatment rather than starting treatment immediately. This is called active surveillance. During active surveillance, the cancer is closely monitored for signs that it is worsening. If the cancer is found to be worsening, treatment will begin.

Active surveillance is usually preferred for men with low-risk prostate cancer that can be treated with surgery or radiation therapy if it shows signs of getting worse. ASCO endorses recommendations from CancerCare Ontario concerning active surveillance, which recommend active surveillance for most patients with a Gleason score of 6 or below, with cancer that has not spread beyond the prostate. Sometimes, active surveillance may be an option for men with a Gleason score of 7. There is also growing use of genomic testing to help determine whether active surveillance is the best choice for a man with prostate cancer.

ASCO encourages the following testing schedule for active surveillance: A PSA test every 3 to 6 months, a DRE at least once every year, another prostate biopsy within 6 to 12 months, then a biopsy at least every 2 to 5 years. A patient should receive treatment if the results of the tests done during active surveillance show signs of the cancer becoming more aggressive or spreading, causes pain, or blocks the urinary tract.

Local treatments get rid of cancer from a specific, limited area of the body. Such treatments include surgery and radiation therapy. For men diagnosed with early-stage prostate cancer, local treatments may get rid of the cancer completely. If the cancer has spread outside the prostate gland, other types of treatment called systemic treatments may be needed to destroy cancer cells located in other parts of the body.

Surgery involves the removal of the prostate and some surrounding healthy tissue during an operation. The type of surgery depends on the stage of the disease, the man’s overall health, and other factors.

A radical prostatectomy is the surgical removal of the entire prostate and the seminal vesicles. Lymph nodes in the pelvic area may also be removed. This operation has the risk of affecting sexual function. Nerve-sparing surgery, when possible, increases the chance that a man can maintain his sexual function after surgery by avoiding surgical damage to the nerves that allow erections and orgasm to occur. Orgasm can occur even if some nerves are cut because these are 2 separate processes. Urinary incontinence is also a possible side effect of radical prostatectomy. To help resume normal sexual function, men can receive drugs, penile implants, or injections. Sometimes, another surgery can fix urinary incontinence.

Robotic or laparoscopic prostatectomy (figure 2) is possibly much less invasive than a radical prostatectomy and may shorten recovery time. A camera and instruments are inserted through small keyhole incisions in the patient’s abdomen. The surgeon then directs the robotic instruments to remove the prostate gland and some surrounding healthy tissue. In general, robotic prostatectomy causes less bleeding and less pain, but the sexual and urinary side effects can be similar to those of a radical (open) prostatectomy. Talk with your doctor about whether your treatment center offers this procedure and how it compares with the results of the radical (open) prostatectomy. Typically, younger or healthier men may benefit more from a prostatectomy. Younger men are also less likely to develop permanent erectile dysfunction and urinary incontinence after a prostatectomy than older men.

Robot Da Vinci

Figure 2: Robot da Vinci

Radiation therapy is the use of high-energy rays to destroy cancer cells.. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. External-beam radiation therapy is the most common type of radiation treatment. The radiation oncologist uses a machine located outside the body to focus a beam of x-rays on the area with the cancer. Some canc er centers use conformal radiation therapy (CRT), in which computers help precisely map the location and shape of the cancer. CRT reduces radiation damage to healthy tissues and organs around the tumor by directing the radiation therapy beam from different directions to focus the dose on the tumor. One method of EBRT used to treat prostate cancer is called hypofractionated radiation therapy. This is when a person receives a higher daily dose of radiation therapy given over a shorter period instead of lower doses given over a longer period. According to recommendations from ASCO, American Society for Radiation Oncology, and American Urological Association, hypofractionated radiation therapy may be an option for the following people with early-stage prostate cancer that has not spread to other parts of the body. People who receive hypofractionated radiation therapy may have a slightly higher risk of some short-term side effects after treatment compared with those who receive regular EBRT. This can include gastrointestinal side effects. Based on current research, people who receive hypofractionated radiation therapy are not at a higher risk of side effects in the long term.

Brachytherapy, or internal radiation therapy, is the insertion of radioactive sources directly into the prostate. These sources, called seeds, give off radiation just around the area where they are inserted and may be left for a short time (high-dose rate) or for a longer time (low-dose rate). Low-dose-rate seeds are left in the prostate permanently and work for up to 1 year after they are inserted. However, how long they work depends on the source of radiation. High-dose-rate brachytherapy is usually left in the body for less than 30 minutes, but it may need to be given more than once. Brachytherapy may be used with other treatments, such as external-beam radiation therapy and/or ADT.

Intensity-modulated radiation therapy (IMRT). IMRT is a type of external-beam radiation therapy that uses CT scans to form a 3D picture of the prostate before treatment. A computer uses this information about the size, shape, and location of the prostate cancer to determine how much radiation is needed to destroy it. With IMRT, high doses of radiation can be directed at the prostate without increasing the risk of damaging nearby organs.

Proton therapy. Proton therapy, also called proton beam therapy, is a type of external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can destroy cancer cells. Current research has not shown that proton therapy provides any more benefit to men with prostate cancer than traditional radiation therapy. It is also more expensive.

Radiation therapy may cause side effects during treatment, including increased urinary urge or frequency; problems with sexual function; problems with bowel function, including diarrhea, rectal discomfort or rectal bleeding; and fatigue. Most of these side effects usually go away after treatment.

To help resume normal sexual function, men can receive drugs, penile implants, or injections. While uncommon, some side effects of radiation therapy may not show up until years after treatment.

The scenario for diagnosis and treatment of prostate cancer has greatly changed in the last 10-5 years. A continuous update in the diagnostic tools and treatment options is extremely necessary.

References

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