Prostate Cancer Therapy in America: A Thorough Guide to Treatment Modalities

Any man confronted with a prostate cancer diagnosis in the United States today is subjected to a vast health care system [situation] that has changed drastically over the last twenty years. The next step, should he decide to proceed, involves stepping into the vast landscape of treatment options he now has in front of him, all of which possess their own considerations, potential outcomes, and implications for quality of life. It is essential that all the treatment options available to him are fully understood by him because this constitutes the first important step in the decision-making process.

The prostate gland is shaped like a walnut, located just under the bladder, and surrounds men's urethras. Although a small gland, it is an important organ in the reproductive system, and when something goes awry in the gland, the ripples spread far beyond the physical disease itself. More than 288,000 men a year receive a diagnosis of prostate cancer in America, making it, after skin cancer, the second most commonly diagnosed cancer among men in the United States.

What makes prostate cancer particularly complicated is that it may behave in an extraordinarily heterogeneous manner. Some tumors start tumor growth slowly, so slowly that they will probably not cause a problem in a man's lifetime, and others behave aggressively and need immediate extensive interventions. A man's range of disease behavior has dramatically impacted how physicians treat the cancer, from active observation to multi-modal aggressive intervention.

Surgery, radiation, and hormone therapy remain key interventions, but many care options have evolved greatly Contemporary oncologists have new imaging modalities that diagnosis cancer with an accuracy that we have never experienced, surgical robots that provide precision to the surgical approach, and targeted therapies that destroy cancer cells while leaving the normal tissues unharmed. Immunotherapy strategies are beginning to demonstrate efficacy in some patients, and genetic screening is helping identify men at higher risk of developing aggressive disease.

Despite all this advancement, one of the biggest paradigm shifts in medical approach to prostate cancer has been theoretical and not technological. The field has moved from a "one size fits all" treatment towards a personalized approach that does not only treat the cancer, but takes into account the patient's age, overall health, life expectancy, values and priorities. A personalized approach acknowledges that the best treatment for one man may not be the right treatment for another even though their cancer may be very similar.

Active surveillance has emerged as a real first line approach for many men with low risk disease. Rather than treating the patient aggressively after diagnosis, men on active surveillance undergo routine monitoring through PSA blood draws, physical examinations, and occasional biopsy. This approach recognizes that many prostate cancers grow slowly enough they are unlikely to be a threat, and moreover that treatments have risks of significant side effects, especially urinary incontinence and erectile dysfunction. If men are under active surveillance and their results start signaling disease progression, treatment options are readily availableGenerally, candidates have PSA levels no higher than ten, a Gleason score of six or less, cancer involving only a little of the prostate, and no high-risk features on biopsy. Ongoing follow-up usually includes follow-up PSA every three to six months, digital rectal examinations, and repeat biopsy, all on a schedule determined by the clinical team. Advanced imaging with multiparametric MRI elevates the active surveillance protocol by providing high-quality pictures of the prostate and by providing more accurate guidance to targeted biopsy of suspicious areas or lesions.

Critics were initially concerned that providing active surveillance would permit cancers to progress beyond the cure window. Yet, robust literature has put those concerns to rest. Long-term studies have shown that cancer-specific survival rates of assuming patient conditions are the same, surveillance patients had the same survival rates as men who receive immediate treatment. The psychological ramifications are also an important consideration. Some men feel reassurance on a day-to-day basis by knowing they are not allowing cancer treatment side effects to affect their quality of life. However, some men may experience anxiety over the fact that they have cancer that is untreated. Counseling and support services assist the patient in managing an emotional component.

When shifting from active surveillance to active treatment, one of the most definitive options available includes radical prostatectomy. The surgical procedure is often defined as removing the entire prostate gland, a small amount of tissue, and the seminal vesicles adjacent to the prostate. The surgeon may also remove some of the nearby lymph nodes to determine whether the cancer has spread. The goal of surgery is to remove all cancer in the body, at least giving men with localized disease the chance of cure.

Surgical techniques

Surgical techniques have changed significantly from open approaches that occurred many decades ago.Laparoscopic prostatectomy is performed utilizing small incisions with specialized instruments and a camera that combines quicker recovery and less blood loss than traditional open surgery is get for surgery. Robotic-assisted laparoscopic prostatectomy is becoming increasingly common, enabling surgeons to control robotic arms that allow for increased visualization and precision with a three-dimensional, magnified view of the surgical field. The da Vinci surgical system is the most utilized system for these procedures, where the surgeon's hand movements are translated into smaller, more precise movements of small instruments inside the patient's body.

Even though robot-assisted surgery offers some of the same benefits as laparoscopic surgery, it entails a hospital stay of typically one to two days, less post-operative pain, blood loss, and resumption of normal activities. Most men can resume light activity within a couple of weeks and can return to work within three to four depending on their line of work. Our outcomes rely heavily on the experience and expertise of the surgeon. Men seeking surgery should be sure to find a surgeon who performs a high volume of surgery and has demonstrated excellent outcomes measuring cancer control and preservation of urinary and sexual function.

There are also challenges in recovery following prostatectomy that each patient should be aware of prior to surgery. Near every man will experience urinary incontinence immediately upon removal of the catheter. Most men will regain continence over the next weeks or months. Pelvic floor exercises, often referred to as Kegel exercises, can help strengthen the muscles which control urination to aid recovery. A very small percent of men will experience some level of incontinence that requires pads or other forms of intervention.Erectile dysfunction is also a common complication because the nerves that control erections run along both sides of the prostate and may be damaged during surgery. The goal of nerve-sparing procedures is to save the nerves when possible with consideration of the location of the cancer. However, even with nerve-sparing procedures, it may take months or years for erectile function to recover. Many men require medications or other means to achieve erections sufficient for intercourse. 

Radiation therapy 

Radiation therapy uses highly energized beams or radioactive sources of energy to kill cancer cells while minimizing damage to normal adjacent tissue. There are different forms of radiation therapy, each with their own characteristics and uses.

External beam radiation therapy takes place from a machine outside of the body. Traditionally, treatment lasted six to eight weeks with daily treatments. However, more modern radiation therapy methods have shortened the duration of treatment while offering effectiveness similar to traditional treatments. Intensity-modulated radiation therapy, or IMRT, takes the radiation beams and mold them to the exact shape and size of the prostate, while varying the dose across the treatment area in a pattern designed to maximize dose to the cancer and protect adjacent organs like the bladder and rectum. Image-guided radiation therapy, commonly referred to as IGRT, involves some form of imaging before each treatment to verify beam placements accounting for changes in the position of the organs from day to day. 

Stereotactic body radiation therapy, or SBRT, is a new technique that provides higher doses of radiation in fewer treatments (typically four to five treatments over one to two weeks, instead of eight weeks).This method, which can also be called stereotactic ablative radiotherapy, requires very precise targeting and complex treatment planning to deliver these high doses safely. The first findings show outcomes similar to standard radiation, but with the considerable benefit of a shorter treatment course. We will need to keep collecting data on long-term follow-up.

Proton beam therapy uses protons instead of X-rays to destroy cancer cells. Protons deliver energy to the tumor at a given depth with minimal radiation beyond the target area, which may lead to fewer side effects due to limiting radiation exposure beyond the tumor, in theory. Proton therapy requires expensive facilities that are not as common as standard radiation facilities and it remains debated whether its theoretical advantages lead to better outcomes for prostate cancer patients. Insurance coverage for proton therapy can be difficult to obtain because some insurance companies continue to call the treatment experimental despite being FDA approved.

Brachytherapy is placing radioactive sources into or near the prostate. Low-dose-rate brachytherapy (often simply called seed implantation) means placing radioactive seeds into the prostate permanently. The seeds are small (about the size of a grain of rice) and are enclosed in titanium. They emit radiation at a diminishing rate over a longer period of time, killing cancer cells nearby. The procedure takes one to two hours and is done under anesthesia, with most men going home the same day. Low-dose-rate brachytherapy is best for low-risk cancers. The outcomes are excellent, and side effects are typically relatively low.High-dose-rate brachytherapy involves temporarily placing stronger radioactive sources into catheters that are situated in the prostate for a very short amount of time. Treatment may take place in one or multiple sessions and the sources are then taken away. High-dose-rate brachytherapy is commonly performed in conjunction with external beam radiation in the treatment of intermediate or high-risk cancer. In this case, the radiation source is used to give the prostate a "boost" in radiation, while the external beam radiation treats the surrounding area. 

Side effects

Side effects from radiation are very different from surgical side effects, and can be equally bothersome. Acute side effects which may occur during or shortly after treatment include urinary urgency, frequency and burning, and bowel urgency and burning diarrhea. These acute side effects typically could last only for a few weeks to a few months after the treatment process has concluded. Long-term side effects could include ongoing bowel or urinary consistent complaints, though persistent bowel or urinary side effects will likely only occur in a small proportion of patients. Many men who have received radiation, will see gradual erectile dysfunction development over time, with erectile dysfunction rates increasing and condensing toward surgical rates by five years post-treatment. Unlike surgery, erectile dysfunction after radiation develops over time, rather than immediately.

In the end, the decision-making process between surgery or radiation generally comes down to patient preference following thoughtful consideration of the ancillary factors involved in making this decision. Surgery may have a psychological advantage by indicating that cancer has been removed from the body, in addition to obtaining pathology information about extent or nature of the cancer, which, unfortunately, imaging cannot supply. Younger men may prefer surgery. Radiation can provide an alternative treatment route due to the avoidance of surgical risks and anesthesia, making it a more appealing option, especially for older men since surgery can pose a higher risk or complicate coexisting medical conditions. Neither treatment option out performs the other in terms of localized cancer control, and both treatments may incur side effects that impact quality of life.Hormone therapy, more correctly called androgen deprivation therapy, takes advantage of the fact that prostate cancer cells typically rely on male hormones such as testosterone for growth. Reducing testosterone levels can shrink tumors, slow their growth, and provide symptom relief. Hormone therapy rarely cures prostate cancer on its own, but there are important settings in which it is a critical component of treatment.

For locally advanced disease, i.e., the cancer has grown outside the prostate but not spread to distant sites, hormone therapy (together with radiation) leads to better outcomes than radiation alone. Treatment is typically continued for two to three years in these situations. For metastatic disease, i.e., disease has spread to lymph nodes, bones, or other organs, hormone therapy is the main form of systemic treatment and can control the cancer for months to years in most men before the disease develops resistance.

There are multiple approaches to achieving testosterone suppression. LHRH (luteinizing hormone-releasing hormone) agonists (e.g., leuprolide and goserelin) are administered via injection every one, three, four, or six months. Initially, LHRH agonists stimulate testosterone production prior to shutting it down. This initial surge may temporarily worsen symptoms in men who have advanced disease, and medications known as antiandrogens are given to block the effects of testosterone during the first few weeks of treatment. LHRH antagonists (e.g., degarelix) function differently by immediately suppressing testosterone without the initial surge.

Orchiectomy, where the testicles are surgically removed, leads to permanent testosterone suppression, and this was the standard approach, but it has largely been replaced by medications that achieve the same hormonal effect without surgery.Some men still prefer this to skip infusions and cost.

Antiandrogens prevent testosterone from attaching to receptors on cancer cells. First-generation antiandrogens, such as bicalutamide, flutamide, and nilutamide, were available decades ago. Newer agents, like enzalutamide, apalutamide, and darolutamide, are stronger and have larger roles in treating later stages of disease. Abiraterone works in a different manner by blocking testosterone from being made throughout the body, including in the cancer cell and adrenal glands.

Hormone therapy sideeffects are due to low testosterone and can include hot flashes, low libido, erectile dysfunction, fatigue, loss of muscle mass and strength, weight gain, breast tenderness and enlargement, and decreased bone density which increases chances of fracture. Other metabolic effects can include increased cholesterol, an increase in insulin resistance, and cardiovascular risk. These side effects can have a significant effect on quality of life, and when deciding to begin hormone therapy, a man must weigh potential benefits versus side effects.

Intermittent hormone therapy, using cycles of going on and off treatment, has been researched as a way to get around side effects, and perhaps delay resistance. During the off-treatment periods, a man's testosterone level can recover and the side effects should improve. He resumes treatment when his PSA rises to an agreed upon level. Studies have shown that many of these men with intermittent hormone therapy can get the same cancer control results as the men that were on continuous therapy, while also improving their quality of life during the off-treatment periods.

Castration resistant prostate cancer is diagnosed when the prostate cancer continues to progress despite hormone therpy maintaining testosterone at castrate levels. This does not mean the prostate cancer does not respond to hormones, and frequently, it does respond. As indicated before, there has been an explosion of new treatment options for prostate cancer, and hopefully for *castration-resistent* prostate cancer and quality of life soon too.

Docetaxel was the first form of chemotherapy to show improved survival in men with metastatic castration-resistant prostate cancer. It is a systemic agent given intravenously every three weeks, for a total of six cycles. The mechanism by docetaxel is an antimitotic agent that disrupts cellular division in general, but should be effective against prostate cancer. Side effects of docetaxel often include fatigue, nausea, hair loss, numbness and tingling of the hands and feet, low white blood cell counts causing an increased risk of infection, and nail changes. When docetaxel is exhausted or the disease progresses after, the second-line chemotherapy is cabazitaxel. Cabazitaxel is also given every three weeks and in men that have progressed after or on docetaxel, improving overall survival.

Sipuleucel-T is an immunotherapy, meaning it is personalized for a man from his own immune cells being used as a vaccine. Simply put, the man has blood drawn through apheresis, the blood is sent to laboratory, where a prostate cancer protein is infused into the immune cells and exposed to them as an antigen, *then returned* to man through an infusion, sometimes with premedication for inflammation; this is repeated for total of three times in a month. Because the clinical trials for Sipuleucel-T first studied it in men with metastatic castration-resistant prostate cancer, it will extend survival in those men; with little side effects, with the exception of flu-like symptoms, when the man detoxed of the infusion of the immune cells. The sequencing of therapy treatment with Sipuleucel-T will continue to evolve as other treatments become more effective.

Radium-233 is an example of a radiopharmaceutical that is classified as internal radiation or targeted radiation therapy, given once monthly for six months by intravenous injection. As simply as possible, radium-233 is an element that mimics calcium and attaches where bones have turnover in men with metastatic castration-resistant prostate cancer, where there is no visceral involvement with other organs like the liver or lungs. In addition to relieving bone pain, it also prolongs survival in metastatic castration-resistant prostate cancer, with little side effects - mainly blood counts dropping.

PARP inhibitors, such as olaparib and rucaparib, are new treatment options in the prostate cancer space for men with tumors that have mutations in DNA repair genes, specifically BRCA1, BRCA2, and other homologous recombination repair genes. These oral medications inhibit repair of DNA damage in cancer cells, resulting in cell death. Identification of patients who may benefit may occur through germline cellular genetic testing (blood sample), and somatic testing (tumor tissue) to identify the alterations detectable by the medications. Patients may experience side effects including but not limited to fatigue, nausea, anemia, and other reductions in blood counts. These PARP inhibitors are a significant step forward in personalized options for prostate cancer.

Checkpoint inhibitors, immunotherapy drugs that let the immune system attack cancer, have changed treatment paradigms for many forms of cancer, but they have generally had limited activity and heterogeneous effects based on tumor features in prostate cancer. The specific program pembrolizumab is helpful for the very few patients whose tumors have high microsatellite instability or mismatch repair deficiency, both genetic features that once present are found in about two percent of advanced prostate cancer. Testing for these features can identify the few men who are likely to respond to this treatment. 

For men with localized disease who are not candidates for or are declining surgery and/or radiation therapy, there may be additional ablative approaches. Cryotherapy is a method in which cancer is destroyed through freezing the prostate tissue with argon gas, which is circulated through needles that are placed in the prostate using ultrasound or MRI guidance. Temperatures are reduced to -40 degrees Celsius with ice balls forming to kill the cancer cells. Specific freezing may be followed by warming cycles. Cryotherapy may be useful in treating the entire prostate or in focal approaches, where only the areas of the prostate that contain cancer are treated. Patients may experience side effects that may include but are not limited to erectile dysfunction, urinary problems, and, rarely, rectal injury. High-intensity focused ultrasound (HIFU) is a form of ultrasound energy used to heat and destroy prostate tissue. A probe is placed in the rectum to deliver focused ultrasound waves to target areas which raise temperature to kill cells. Similar to cryotherapy, HIFO may be used to treat cancerous prostate tissue anywhere from the entire prostate to just target areas. HIFU has been available for years in Europe; however, the device received FDA approval in the United States for ablating prostate cancer tissue more recently. Compared to established treatments, long-term cancer control data for HIFU is limited and it is not uniformly covered by insurance.

Focal therapy is an emerging strategy to treat only the cancerous areas of the prostate while preserving the remainder of the prostate and surrounding structures. Similar to lumpectomy for breast cancer, focal therapy is similar in that it tries to provide cancer control with less side effects than treating the entire gland and, instead, just target areas. HIFU, cryotherapy, laser, photodynamic therapy, and irreversible electroporation are examples of focal treatment which create a localized heat. The barrier to better treating prostate cancer using focal therapy is being able to accurately identify all cancer in the prostate and ensuring targeted areas are treated completely. It has been helpful to develop multiparametric MRI, which has improved localization to some degree, but given that the sensitivity is still imperfect, there will still be cancers that get missed as well. Focal therapy remains investigational at most centers, and is ongoing trials evaluating outcomes.

Management of side effects of treatment

Another key aspect of comprehensive prostate cancer care is the management of side effects of treatment. After surgery, urinary incontinence can also be managed in part by pelvic floor physical therapy which entails doing specific exercises to strengthen the pelvic muscles that control urination. There are behavioral strategies such as: timed voiding, double voiding, and urgency suppression which can be helpful. In some cases, medications may help reduce bladder overactivity when conservative management fails.There are a range of treatment options for persistent urinary incontinence such as injectable bulking agents to help support the closure of the urethra, external compression devices or surgical treatments such as urethral slings or devices such as an artificial urinary sphincter.

When it comes to erectile dysfunction which can result from the treatment of prostate cancer, there are also many options for management. Exercise medication which are part of a class called phosphodiesterase-5 inhibitors including sildenafil, tadalafil, and vardenafil, are all first line therapy for many men. The bottle these medications works by increasing blood flow to the penis and improving the erectile response to sexual stimuli. Starting this medication soon after treatment even before the man starts to have spontaneous erections may be helpful for preserving the health of erectile tissue. If oral medications are unsuccessful in restoring erectile function, doctors have other options including intracavernosal injections of medication such as alprostadil either by itself or in combination with other medications to produce an erection. Men self inject medication into the side of the penis prior to sexual activity. An alternative feasible option is inserting intraurethral suppositories (medication into the urethra) for an erection either as single drug or in combination with oral medication you may also be taking prior to sexual activity. A vacuum erective device uses negative pressure to draw blood to the penis with a constriction ring to support the erection. If a man has failed all other management approaches there are commercially available devices surgically placed in the penis to allow men to "mechanically" achieve an erection providing a permanent solutions for men who have failed all other options to coitus.

Many men discover their journey of restoring sexual intimacy from the effects of prostate cancer treatment requires re-defining sexuality more broadly than penetrative sexual intercourse. Talking with a sexual medicine specialists or therapist trained in restorative intimacy can be good partners to help couples navigate through these changes or adjustments in intimacy to ensure a sustained physical connection and emotional connection with each other.

In men receiving long-term hormone treatment attention to bone health is also important. Testosterone deficiency contributes to accelerated bone loss with potential for increased fractures.Obtaining baseline bone density measuring and follow up studies may be a good option to monitor for changes.Taking calcium and vitamin D, engaging in weight-bearing activities, and fall prevention programs can help individuals maintain bone health. When a bone density test indicates osteoporosis, medications like bisphosphonates or denosumab are effective treatments for maintaining and possibly increasing bone density and decreasing the risk of osteoporotic fractures. These same treatment agents can help decrease skeletal-related events in men who have a diagnosis of prostate cancer and bone metastases.

Cardiovascular health should be monitored during hormone therapy due to the link between testosterone suppression and increased cardiovascular risk. It is even more important to manage the traditional cardiovascular risk factors, such as diet, physical activity, weight, hypertension, cholesterol, and diabetes; some men may want to consult with a cardiologist prior to starting hormone therapy if they have pre-existing cardiac disease.

Fatigue is a common, and often troubling, side effect seen during many types of treatment. While rest is an important aspect, long periods of inactivity can also contribute to fatigue exacerbation. Structured exercise programs incorporating both aerobic and resistance can help with cancer related fatigue resolve and provide improvements in quality of life, strength and overall physical function. Programs promoting oncology rehabilitation can provide individual assessments for design a safe and effective exercise programs based on ability and limitations.

Nutritional factors

Nutritional factors have always been part of the cancer journey, from before treatment, through active treatment, and then through recovery. During the active treatment phase, maintaining an adequate caloric and protein intake can help to preserve strength and support the healing process. Men who may have treatment related nausea, taste changes, or appetite may benefit from working with oncology dietitians, who can help better manage nutrition. After acute treatment, questions may arise if changes in diet can slow the tumor growth or reduce the incidence of recurrence.Although a specific diet cannot cure prostate cancer, results are indicative that a healthy dietary pattern, which includes plenty of vegetables; fruits; whole grains; and healthy fats; while limiting red and processed meats; may improve overall health and potentially improve overall prostate cancer-related outcomes. Obesity has been associated with more aggressive prostate cancer, offering some additional motivation for men with prostate cancer to eat well and exercise to maintain healthy weight.

Many men with prostate cancer find complementary therapies - including acupuncture; massage; yoga; meditation; and mindfulness practices - are useful in coping with stress, symptom management, and improving overall wellbeing. In general, the best application of complementary therapies is in conjunction with mainstream medical treatment, rather than throwing out conventional therapy. Men with prostate cancer should always inform their medical teams of any complementary wearable health technology they use, associated supplements, or therapies they are used because some supplements might affect the effectiveness of conventional treatments or could cause significant adverse effect. Although I can understand the appeal for "natural" treatments, the decision to treat cancer should only be founded on the body of evidence to support the treatment as potentially effective and examine by the particular expert clinician for safety.

Although probably not available to everyone, clinical trials offer men/people with prostate cancer the potential to access several promising new treatments before they are available to wider cancer populations. All clinical trials will have phases where phase one studies look at the safety and dose and allow healthy men to participate, phase two studies to see efficacy to the disease may only have a small number of men participate, and phase three studies of any treatment will be with large populations where one or more new treatment is compared to the current standard of care of two or more therapies. Participating in a clinical trial not only advances the protocols of treatment for the next patient, but it also offers men access to treatment or technology that offers the chance of better outcomes than those established. Many men worry or concern about being assigned some placebo to their treatments and this is usually not justified in cancer clinical trials where the selection for the control used, will alter in different phases of studies when there is a potential new treatment. Each trial will have key eligibility needs to allow a large selection to participate in; however, it will take time, support, and diligence to consider in risking decisions on the risks and benefits of participation. The National Cancer Institute’s homepage has an extensive database of cancer clinical trials and many cancer centers have offices dedicated to clinical trials to assist patients in identifying clinical trials for their diagnosis.

Biomarker testing has become increasingly important in treatment decisions for cancer care. PSA, the most familiar prostate cancer biomarker, remains less than perfect, as an elevated value can result from benign conditions, and some cancers create little to no PSA. The newer tests provide additional information. Genomic tests, which analyze tumor tissue, such as Oncotype DX Prostate, Prolaris, and Decipher are tests that assess patterns of gene expression that predict aggressiveness and outcomes of the cancer. These tests help us utilize the assessment of risks and treatment decisions, particularly who requires treatment versus surveillance and whether to use hormone therapy with radiation. Liquid biopsies, which target circulating tumor cells or tumor DNA fragments present in blood, are a new technology for tumor monitoring measures to evaluate treatment response and detect recurrence. 

Genetic testing of normal tissue to identify inherited mutations associated with risk to develop cancer has also become increasingly relevant. About ten percent of prostate cancer is related to inherited genetics. BRCA1, BRCA2, ATM, and CHEK2 mutations and others can increase the risk of developing prostate cancer. The mutations may also be a marker for more aggressive disease that require more intensive treatment. Additionally, there can be implications for family member risk of cancer, and in some situations, the genetics can be associated with the treatment decision (i.e., PARP inhibitor therapy). Current recommendations are for genetic counseling and testing if a man has metastatic prostate cancer, high-risk localized disease with family history, and anybody with family history compatible with hereditary cancer.

Having a disease recurrence after successful treatment will be a very difficult situation and will require a thorough evaluation.Biochemical recurrence occurs when PSA or prostate-specific antigen rises following treatment, and it means the presence of cancer before being able to detect it using clinical methods due to the elevated PSA. After a prostatectomy, when PSA is detectable, it implies either persistence of cancer or that there has been a recurrence since the prostate should no longer be present. After radiation, a low PSA level is expected, and the definition of recurrence is rising two points about the lowest PSA following treatment. While PSA kinetics, including rapid doubling time, and the time from treatment to recurrence can suggest aggressive disease, cut-off values have not yet been established. However, it is clear that low PSA doubling times and short time periods from treatment to recurrence indicate the likely presence of more aggressive disease.

Imaging studies

Imaging studies are useful in determining the localization of recurrent disease. Traditional imaging studies such as CT and bone scans are often unsedated, detecting cancer with low PSA levels, while, newer imaging techniques offer enhanced sensitivity. Multiparametric MRI can provide the detection of local recurrence. Systems using positron emission tomography (PET) with certain levels of tracers have been demonstrated to be remarkably able to detect recurrent prostate cancer. PET scanning with fluciclovine F18 detects cancer through amino acids in tissue uptake. PSMA PET imaging with tracers showing binding to prostate-specific membrane antigen expressed on cancer cells has shown marvellous sensitivity for detecting the disease and will in fact detect disease at extremely low levels of PSA. Several PSMA PET tracers have come to market and gained FDA approval. As an imaging methodology, PSMA PET is changing the management of recurrent disease not only sort of identifying the location of disease, but also guiding treatment options.

The treatments offered for recurrent disease is dependent on the initial treatment and the location of the recurrence. Men with surgery to remove the prostate who develop recurrence generally may benefit from radiation to the prostate bed, and sometimes in concert with hormone therapy. Men who relapse after radiation treatment may have a more difficult time finding options, especially with a local recurrence as the earlier treatment has radiated the area.Salvage prostatectomy, which involves surgically removing locally recurrent cancer after radiation, can be complex and has higher risk of complications, but in selected patients these procedures may cure. Salvage cryotherapy of HIFU represent alternative treatment options. When cancer recurrence is limited to the pelvic lymph nodes, combining surgery or radiation targeting the affected nodes maybe an effective way to control the disease. More diffuse patterns of metastases are more likely related to systemic disease that would need systemic therapy with hormone therapy, with other agents to follow as patients progress through systemic therapy. 

An area of care we see as transitioning into the future of care for men receiving treatment for prostate cancer is the oligometastatic state. Here, the patient's cancer has progressed but has limited systemic disease. There is growing evidence that these limited metastases may be treated with radiation and/or surgery, a treatment approach called metastasis directed therapy, which may prolong time before systemic therapy is indicated, and a systemic therapy only approach is warranted. This pushes against traditional thinking that once cancer becomes systemic, the only option must be systemic therapy. 

Palliative care is often confused with hospice or end of life care; however, palliative care is specialized medical care, which provides relief from the symptoms and stress of a serious illness; and this care is appropriate at any illness stage and is appropriate to offer alongside curative treatment. A standard palliative care team often includes specialist physicians, nurses, social workers, and other specialists who strive to improve the quality of life for patients and their families through treatment of physical symptoms, emotional, spiritual needs, and practical issues. Studies have shown early integration of palliative care will improve quality of life, possibly longevity of life, and assures care is aligned with patients values/and goals. 

Hospice care

Hospice care is specific to the patient when the goal is comfort and improvement in quality of life at the end of life, when cure is no longer possible, and when the patient has a life expectancy of six months or less.Hospice serves as a holistic support system in the home, or wherever appropriate, to manage symptoms, provide emotional and spiritual support, and help families through the dying process and grief process. To enter hospice care signifies a transfer of treatment from life-prolonging efforts to a focus on comfort and quality of life. While a difficult decision for many men and families, determining to enter hospice care can eventually help provide comfort and dignity at the end of life.

Survivorship care addresses the needs of the growing number of men living with and beyond prostate cancer. In fact, over 3 million men living in the US today have been diagnosed with prostate cancer and are alive. Survivorship care includes managing the side effects of treatment, monitoring for recurrence of cancer, preventing the occurrence of secondary cancers and other health issues, in addition to addressing psychological, social, vocational, and financial aspects resulting from cancer. A care plan for survivorship provides a summary of the treatment received, suggestions for follow-up care, and ways to coordinate the care of the oncologist and primary care provider. Support groups, in-person or virtually, assist connecting men with other men experiencing a similar situation to provide practical advice and emotional support.

The psychological ramifications of prostate cancer deserve recognition and consideration. For men during treatment and beyond, anxiety and depression are common issues that can occur. Anxiety and depression can arise from uncertainty about the future, feelings of loss of function and independence, changes in self-image and relationships, and existential issues about what is meaningful and life and dying. Professional counseling and support groups, as well as peer support programs and when needed medications for anxiety and depression, are helpful in navigating anxiety or depression. Partners and family members also experience significant stress and may benefit from support services.

The disparities of prostate cancer outcome persist and are troubling.African American men experience the highest prostate cancer incidence and mortality rates in the United States, with death rates at least twice those of white men. There are numerous factors that contribute to these disparities, such as differential access to care, screening rates, inherited genetic factors, socioeconomic factors that influence health behaviors and treatment compliance, and potentially biases in the provision of health care. Addressing these disparities requires systemic changes to ensure all men, regardless of race, ethnicity, or socioeconomic status, have equitable access to prevention, screening, treatment, and supportive care.

Financial toxicity reflects the financial burden and distress associated with cancer treatment. Financial toxicity burdens countless patients and families. Even with insurance coverage, patients often have significant out-of-pocket costs, such as deductibles and copays for medications, as well as indirect costs like lost wages and transportation. Financial distress often leads to treatment nonadherence, depleted savings, debt, and decreased quality of life. The oncology social worker and patient navigator can assist patients by locating financial assistance programs, negotiate reduced medical bills, and provide information about community resources. Open communication related to financial worries with the patient and medical team also allows the medical team to develop the least expensive treatment options when appropriate medically.

As we look to the future, prostate cancer research continues to advance on several fronts. Continued advancements in the biological understanding of cancer at the molecular level inform additional therapeutic intent or targets. The continued advent and growth of precision medicine will aim to match treatment approaches to individual tumor biology or characteristics, with the ultimate goal of improving outcomes and sparing ineffective therapies from patients.Both AI and machine learning are being utilized to enhance cancer diagnosis, predict outcomes, and personalize therapy. New imaging technologies provide more extensive information on the extent and biology of the cancer. Programmed combinations of therapies that simultaneously attack the cancer through multiple mechanisms are being used and are expected to improve cure rates and advance disease control. Therapies utilizing vaccines and other immunologic approaches are under development with the hope of using the immune system against prostate cancer more effectively.

Prevention remains an important area of investigation. Risk factors such as age, race, and a family history of prostate cancer are nonmodifiable; however, some may lead to intervention. Research continues into dietary risk factors, activity level, medications such as finasteride and dutasteride that lower the incidence of prostate cancer, and environmental exposures. A better understanding of genetic risk factors may allow for early screening and prevention approaches for high-risk men.

The change in the care of prostate cancer over the last few decades has been amazing; the treatment of what was once a disease with little to offer patients has transitioned to multiple effective treatments at all stages of the disease. Mortality rates have been greatly reduced. More men are diagnosed with early-stage disease through screening, but the utility of screening continues to be debated. Although treatment-related adverse effects are still a very important issue, they have reduced due to technical advances and better patient selection. The number of treatment options available for metastatic disease has enabled men to live for years longer with metastatic cancer.

However, challenges remain.Despite broader use of active surveillance, overtreatment of indolent cancers persists. Even with improved treatment for aggressive cancers this still occurs, and understanding why some cancers behave aggressively while others do not is still not fully understood. The side effects of treatment, particularly sexual and urinary dysfunction, continue to impact quality of life. Disparities in outcomes remain. Healthcare costs continue to rise and patients without much income left may be driven away from treatment for cancer by costs. 

For men diagnosed with prostate cancer, the first step is education and honest discussion with providers. There is no "one-size-fits-all" approach to treatment. The best approach will depend on the cancer characteristics, the patient, values and preferences, and resources available. Seeking a second opinion from a urologic oncologist with a breadth of knowledge can provide perspective, education, and confidence in treatment approaches. Building a healthcare team including urologists, radiation oncologists, medical oncologists, primary care providers, and supportive care providers helps pakcaged patients with a coordinated approach from patients and his liason to family support.

Final

While the patient journey is still a path within which the patient remains hopeful yet realistic the challenges placed definitively in front of them.Many men diagnosed with prostate cancer are medically cured and they go on to either live a normal life or years with a manageable disease like a chronic disease.It is also possible to have an advanced disease diagnosis and still have meaningful time intervening with family and friends, continue achieve important life goals, and maintain a quality of life. A medical team highly invested in not just treating a cancer diagnosis but treating a person with the cultural background, living patterns, emotional patterns, and knowledge of a journey of cancer can be very difficult as it is its own journey in the cancer experience. Making that journey less difficult is their goal. 

The promise regarding care for prostate cancer is the evolution of care stemming largely from the collaborative work of researchers, clinicians and staff and clinical trialists and advocate organizations. Continued evolution of care is evident as time continues from sharing knowledge gained and the discovery of care options and treatment options evolve.It is warranted to mention again that no one wishes to be diagnosed with a cancer of any type. Yet, men today facing diagnosis of prostate cancer have more reason to be hopeful than ever before. The combination of knowledge, support from experts, familary and other patient support, and overall intentional attention to quality of life through treatment options empowers men to navigate the challenges of their diagnosis while feeling hopeful about the next leg of their journey.