Overview of approach to prostate cancer survivors

INTRODUCTION — The number of cancer survivors living in the United States continues to increase each year. Prostate cancer is a common cancer, and because it is frequently an indolent disease and modern treatments have improved survival, the population of survivors is growing and aging. It is estimated that there were more than 3.5 million males with a history of prostate cancer living in the United States as of January 1, 2022 [1].

Prostate cancer survivors may be cared for by oncologists, urologists, and/or primary care providers (PCPs). Prostate cancer survivorship care guidelines were published by the American Cancer Society in 2014 [2] and subsequently, relevant primary care issues were reviewed in 2016 [3]. This topic will incorporate and update these guidelines with the goal of informing a rational approach to the care of the prostate cancer survivor and their partner. The information provided is targeted at both specialists and PCPs, who are increasingly confronted with managing survivorship issues in patients with a history of cancer. A general overview of cancer survivorship care for primary care and oncology providers is presented elsewhere. (See "Overview of cancer survivorship care for primary care and oncology providers".)

EPIDEMIOLOGY — Prostate cancer is the most common non-skin cancer in American men; one in eight males will be diagnosed during their lifetime [4]. The average age at diagnosis is 66, and 60 percent of all cases are diagnosed after age 65. Although generally considered a disease of older men, the incidence of prostate cancer has been increasing globally in both adolescents and younger males [5]. (See "Risk factors for prostate cancer", section on 'Age'.)

APPROACH TO CANCER SURVIVORSHIP

Definition — The term "cancer survivor" has been used variably in the literature; most commonly, a cancer survivor refers to any person who has been diagnosed with cancer. Therefore, survivorship begins at the time of diagnosis and includes the periods of initial treatment with intent to cure, cancer-free survival, chronic or intermittent disease, and end-of-life care [6].This definition is consistent with those provided by The National Coalition for Cancer Survivorship [7] and the National Cancer Institute, which define a person as a cancer survivor from the moment of a cancer diagnosis through the balance of their life.

General components of survivorship care — The transition from active treatment to post-treatment care is critical to long-term health. A committee established by the Institute of Medicine to examine the range of medical and psychosocial issues faced by cancer survivors recommended the following components of survivorship care [6]:

●Surveillance for cancer recurrence or second cancers

●Prevention of recurrent and new cancers and of other late effects

●Assessment of medical and psychosocial late effects and consequences of cancer and its treatment. As examples:

•Medical problems such as bowel problems and sexual and urinary dysfunction;

•Symptoms, including persistent pain and fatigue;

•Psychologic distress experienced by cancer survivors and their caregivers;

•Concerns related to employment, insurance, and disability

●Coordination between specialists and primary care providers (PCPs) to ensure that all of the survivor's health needs are met (see 'Coordination of follow-up care' below)

Issues that pertain to routine cancer screening and preventive care, and management of comorbid conditions in cancer survivors in general are discussed elsewhere. (See "Overview of cancer survivorship care for primary care and oncology providers".)

Issues specific to prostate cancer survivors

Coordination of follow-up care — Following treatment, patients should undergo ongoing assessments for treatment-related side effects [2,3], as well as preventive and general health care [8-10]. Therefore, it is important for cancer specialists (urologists and medical and/or radiation oncologists) and PCPs to clearly communicate who will take responsibility for the different aspects of cancer surveillance to avoid duplicate prostate-specific antigen (PSA) testing, and the thresholds for referral back to specialty care. This may be done in the form of a treatment summary (from the treating providers to the PCP) or may be contained in the surveillance portion of a survivorship care plan. (See "Follow-up surveillance after definitive local treatment for prostate cancer" and "Assuring quality of care for cancer survivors: The survivorship care plan".)

General principles guiding follow-up

●Clinicians should ensure that appropriate testing is being done to monitor for disease progression/recurrence both during and after treatment. Post-treatment cancer surveillance generally includes periodic PSA testing. If the PSA begins to rise, another PSA should be drawn a month later with explicit instructions to avoid ejaculation or trauma to the perineum (bicycle or motorcycle riding) with 48 hours of the repeat blood test. Confirmation of a rising PSA should prompt referral back to the specialist for further workup and staging. (See 'Monitoring for recurrence and/or disease progression' below.)

●In addition to routine interval history and physical examination, other aspects of follow-up should include an attention to cardiovascular health, with screening and management strategies that are similar to guidelines for the general population. Males diagnosed with prostate cancer have a greater incidence of cardiovascular disease than age matched males without prostate cancer [11,12]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

●Quality of life surveillance should ideally be performed periodically. This can be done using a validated one page instrument that addresses urinary, sexual, bowel, and vitality domains (eg, Expanded Prostate Cancer Index Composite for Clinical Practice [EPIC-CP]) [13].

●Periodic evaluation and management of the patient for sexual dysfunction should also include partner evaluation, if the patient has a partner, and referral to a sexual health clinician if warranted. Screening and assessment of male sexual dysfunction should utilize one of several validated instruments, such as the International Index of Erectile Dysfunction (IIEF, (table 1), or the Sexual Health Inventory for Men, also called IIEF-5 (table 2). The subject of screening for sexual dysfunction in male cancer survivors is discussed in detail separately, and a discussion of sexual dysfunction following prostate cancer treatment specifically is presented below. (See "Overview of sexual dysfunction in male cancer survivors", section on 'Sexual health questionnaires' and 'Sexual dysfunction' below.)

●In addition to these issues, general guidelines for the follow-up of cancer survivors, including encouragement of a healthy lifestyle, should also be discussed with patients. These include:

•Dietary modification towards micronutrient-rich and phytochemical-rich vegetables and fruits, low amounts of saturated fat, at least 600 international units of vitamin D daily, and adequate amounts of dietary sources of calcium (ie, not to exceed 1200 mg/day), per American Cancer Society (ACS) Nutrition and Physical Activity guidelines for cancer survivors [14]. (See "The roles of diet, physical activity, and body weight in cancer survivors".)

•Physical activity/exercise is a vital component to improve or maintain general health as well as to mitigate the side effects of androgen deprivation therapy (ADT). (See 'Overview of specific major side effects' below.)

Randomized trials in males receiving ADT have shown that exercise benefits muscle mass and strength, body composition, fatigue/energy level, quality of life, physical functioning, social functioning, psychologic distress, bone health, comorbid disease risk factors, sexual well-being, bone pain, urinary problems, and cognitive decline [15].

Consistent with ACS Nutrition and Physical Activity guidelines for cancer survivors [14], survivors without physical limitations or contraindications should aim for at least 150 minutes per week of moderate-intensity exercise or 75 minutes per week of vigorous-intensity aerobic physical activity or an equivalent combination of moderate- and vigorous-intensity aerobic physical activity, which should also include routine resistance exercises. Those with physical limitations, including metastatic disease, should be supervised by an exercise physiologist with expertise in treating cancer patients for a personalized exercise prescription [16].

These recommendations are also supported by year 2019 evidence-based recommendations from the American College of Sports Medicine in conjunction with the ACS and National Cancer institute that encourage the systematic use of an "exercise prescription" by health care workers and fitness professionals for people living with and beyond cancer [17-19].

•Although excess consumption of alcohol should be avoided, at least some data from the Health Professionals Follow-Up Study support the view that moderate consumption of alcohol (15 to 30 g/day of total alcohol) is safe in males with a diagnosis of prostate cancer [20]. Fourteen to 15 g of alcohol (0.5 to 0.6 fluid ounces) is equivalent to 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80 proof liquor.

•Smoking cessation strategies should be encouraged for general health benefits in all men. However, prostate cancer survivors should be advised that smoking is associated with an increased risk of recurrence and mortality after radical prostatectomy [21].

These topics are all discussed in more detail separately. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Components of posttreatment follow-up' and "Overview of cancer survivorship care for primary care and oncology providers", section on 'Limitation in alcohol consumption' and "The roles of diet, physical activity, and body weight in cancer survivors".)

OVERVIEW OF PROSTATE CANCER TREATMENT OPTIONS — The initial management of males with newly diagnosed prostate cancer depends on disease extent and an estimation of the risk of disease progression to disseminated, potentially fatal disease. Clinical staging is based on a digital rectal examination by an experienced clinician to assess the extent of disease, the pretreatment serum prostate-specific antigen (PSA), the Gleason grade group in the initial biopsy (table 3), and the extent of cancer involvement in the biopsy cores. This information allows the stratification of males into specific risk categories for disease progression. Most clinicians in North America use the risk categories as defined by the National Comprehensive Cancer Network (table 4), which have been used in multiple professional society guidelines [22-26], but other risk stratification systems are in use [27]. (See "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'Risk stratification'.)

Imaging studies (radionuclide bone scan, computed tomography of the abdomen and pelvis, multiparametric magnetic resonance imaging) are used selectively to assess for extraprostatic extension, regional adenopathy, or distant metastases, depending on the initial clinical staging and estimate of risk; pretreatment imaging for distant metastases is not routinely recommended for very low- and low-risk disease according to the clinical staging system described above, while it is recommended for more advanced disease. On the basis of imaging, patients can be further classified as having regional (pelvic nodes) or metastatic (distant sites or lymph nodes above the bifurcation) disease. (See "Initial staging and evaluation of males with newly diagnosed prostate cancer".)

Localized disease — Treatment decisions for localized prostate cancer are complicated and preference sensitive because of the differences in the specific risks and benefits of the various treatment choices (table 5). Patient-clinician shared decision making can facilitate selecting a treatment that best aligns with the patient's personal values, and it is recommended in professional society guidelines. A particularly useful tool can be found on the website Patient Priorities Care, which was developed to help patients and their clinicians focus on what matters most, and their own health priorities. (See "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'Importance of shared decision making'.)

Active surveillance versus watchful waiting — In the older literature, the terms "active surveillance" and "watchful waiting" were often used interchangeably; however, distinctions in current terminology need highlighting. Active surveillance (AS) is an option for males whose prostate cancer is very low-risk or low-risk prostate cancer; the best candidates have disease that is confined to the prostate gland, Gleason grade group 1 or 2 (table 3), low volume tumors, and a PSA <10 ng/mL. AS avoids or postpones immediate therapy but requires careful surveillance. Definitive treatment is then offered if there is evidence that the patient has developed an increased risk for disease progression. AS for low-risk disease can potentially spare males from the toxicities and sequelae associated with immediate definitive treatment. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Rationale for active surveillance'.)

AS differs from another form of expectant management, "watchful waiting." Whereas AS assumes action will be taken if there is increased risk for disease progression, watchful waiting is based on the premise that males will not benefit from definitive treatment of clinically localized prostate cancer because of limited life expectancy, comorbidity, and the prolonged natural history of prostate cancer [28]. For males managed with watchful waiting, the decision is made at the outset to forego definitive treatment and to provide local or systemic treatment to palliate symptoms if disease becomes symptomatic. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Active surveillance versus watchful waiting'.)

Although males can be potentially spared from the toxicities associated with immediate definitive treatment, AS may still impact quality of life:

●Males who are managed with AS have the psychosocial burden of living with an indolent cancer without active treatment. In some studies, general anxiety and distress appears to lessen over time [29], while in others it increases [30], and may result in transitioning from AS to active therapy in up to 5 to 20 percent of cases, even in the absence of disease progression [29,31]. The impact of AS on the man's partner, however, has not been well studied, although anecdotally it appears that the partner may experience even higher anxiety than the patient. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Quality of life issues and psychologic comfort with surveillance'.)

●Another issue is that repeat prostate biopsies with AS protocols have also been associated with slight increases in erectile dysfunction over time [32,33]. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Role of repeat biopsy and MRI during longitudinal follow-up'.)

Active treatment options — Males who are candidates for definitive therapy (including those with regional nodes) and selected males with oligometastatic disease should have the opportunity to discuss each active treatment modality (surgery, brachytherapy, external beam radiation therapy) with the urologist and radiation oncologist. Males may also seek advice from their primary care provider or a medical oncologist who specializes in prostate cancer.

●Radical prostatectomy – Radical prostatectomy (RP) is an option for males with a life expectancy of at least 10 years. In general, the experience of the surgeon should be the critical factor in choosing an operative approach (open or robotic). In addition, a pelvic node dissection is often performed for selected males with unfavorable intermediate- or high-risk disease. (See "Radical prostatectomy for localized prostate cancer" and "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement", section on 'Radical prostatectomy'.)

Some males with high-risk resected disease may be offered a course of adjuvant RT with or without androgen deprivation therapy (ADT); however, current practice is shifting more toward early salvage RT (at the time of a rising PSA) rather than adjuvant RT. (See "Prostate cancer: Postoperative management of pathologic stage T3 disease, positive surgical margins, and lymph node involvement following radical prostatectomy", section on 'RT: adjuvant versus early salvage'.)

●Radiation therapy – For males with localized prostate cancer, radiation therapy (RT) is a reasonable alternative to RP. RT can be delivered as photons, protons, or radioisotopes (brachytherapy). In the United States, intensity-modulated RT is the most common form of external beam radiation. Stereotactic body RT (SBRT) is a very precise delivery of intense dose radiation given over a short period of time. The energy from standard photon or SBRT is from photons, whereas the energy source for proton RT is from protons. Brachytherapy delivers energy directly to the prostate by radioisotope sources, usually iodine-125 or palladium-103, that are injected into the prostate on either a temporary or permanent basis. (See "External beam radiation therapy for localized prostate cancer" and "Brachytherapy for low-risk or favorable intermediate-risk, clinically localized prostate cancer".)

Most males who undergo definitive RT for intermediate- or high-risk prostate cancer are also treated with ADT, which is typically initiated from two to eight months prior the initiation of RT, continued through RT, and continued thereafter. At many institutions, males with high-risk disease are treated with a longer duration of ADT than are those with intermediate-risk disease. This subject is addressed elsewhere. (See "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement", section on 'Sequencing and duration'.)

Disseminated metastases — The initial approach to the management of the individual who presents with de novo disseminated metastases (M1) focuses on ADT, with either a so-called "medical orchiectomy" (using gonadotropin-releasing hormone agonists or antagonists) or bilateral orchiectomy. In the man who is "hormone naïve" this presentation is called metastatic "hormone sensitive" (or castration sensitive) disease. Based on several contemporary phase III trials showing survival benefit with the addition of docetaxel, abiraterone, enzalutamide, or apalutamide to ADT, many males are treated with one of those combinations rather than ADT alone [34]. (See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer".)

The vast majority of males treated with ADT for hormone/castration sensitive advanced prostate cancer will eventually develop disease progression, although the natural history may be prolonged. If the serum testosterone level at that time is at castrate levels (<50 ng/dL) the disease is referred to as "castration resistant" prostate cancer. (See "Overview of the treatment of castration-resistant prostate cancer (CRPC)".)

Prognosis — Overall survival for males with local or locally advanced prostate cancer is typically prolonged, with the 5-, 10-, and 15-year relative survival rates of 98 percent, 98 percent, and 96 percent, respectively, for those diagnosed with localized disease.

Even males who are conservatively treated for localized disease may have prolonged survival, and the figure (figure 1) shows the impact of age at diagnosis, Gleason score, and primary tumor (T) stage on 15-year prostate cancer specific mortality compared with mortality due to competing causes in older males who were not originally treated at the time of diagnosis [35].

For males with metastatic disease, most will die of prostate cancer, but approximately 30 and 10 percent will still be at alive at 5 and 10 years, respectively [36]. Males with metastatic hormone sensitive disease have varied median overall survival times which ranged from 13 to 75 months in one study of 1345 males who were all treated with ADT [37].

TREATMENT-RELATED SEQUELAE

RT and prostatectomy

Sexual dysfunction — Males should be informed prior to therapy that sexual function is likely to be permanently altered after any form of treatment for prostate cancer.

●Erectile dysfunction – Erectile dysfunction (ED) is the most common treatment-related side effect for males with prostate cancer and becomes evident immediately after surgery in most men. Some recovery is often observed during the first year or two after surgery. By contrast, after radiation therapy (RT), ED may not be evident for two to three years or later [38,39]. (See "Radical prostatectomy for localized prostate cancer", section on 'Erectile dysfunction' and "External beam radiation therapy for localized prostate cancer", section on 'Sexual dysfunction'.)

•Risk – Because measures of sexual outcomes after surgery or RT are not standardized, rates of ED reported in the literature are highly variable [40]. However, ED is common after prostatectomy, with estimates ranging from 27 to 77 percent. (See "Overview of sexual dysfunction in male cancer survivors", section on 'Prostate cancer'.)

For males undergoing prostatectomy, an alternative outcome measure is rate of return of erections to baseline prior to surgery. When measured by modified International Index of Erectile Function score (table 1) in 210 patients who had radical prostatectomy (RP), 7 percent of the overall population reported return of erectile function to baseline, and in those who underwent bilateral nerve sparing, this number rose to 16 percent [41]. (See "Radical prostatectomy for localized prostate cancer", section on 'Nerve-sparing approach' and "Radical prostatectomy for localized prostate cancer", section on 'Incidence and time course'.)

For males treated with external beam RT, the frequency of new-onset ED following therapy is also variable for the same reasons noted above. In contemporary series, approximately 30 to 45 percent of males who have erections prior to RT develop ED after therapy, with the frequency increasing over time so that by five years the rates of ED are approximately the same as those after RP [42]. (See "External beam radiation therapy for localized prostate cancer", section on 'Sexual dysfunction'.)

•Management – Despite the high percentage of males who have sexual dysfunction symptoms after treatment of localized prostate cancer, a significant proportion may not seek a consultation. In a study of males with ED after therapy, 48 percent of males had been treated with brachytherapy, 61 percent of those treated with external beam RT, and 23 percent of males who underwent a RP had never tried commonly available medications or devices to improve their erections [43]. Barriers to consultation and treatment require further evaluation, but these data highlight the need for proactive screening to identify sexual health complaints. Screening could be as simple as asking the question about erectile function and whether it is adequate for satisfactory sexual relations or administration of a short questionnaire such as the EPIC-CP [13].

For male cancer survivors who want to pursue therapy for ED, referral to a sexual rehabilitation program is appropriate. These programs are typically run in specialized men's sexual health programs and utilize phosphodiesterase-5 (PDE-5) inhibitors, vacuum erection devices, intraurethral and intracorporal prostaglandins, and/or surgical placement of penile prostheses. (See "Overview of sexual dysfunction in male cancer survivors", section on 'Management' and "Treatment of male sexual dysfunction" and "Surgical treatment of erectile dysfunction".)

Agents such as the PDE-5 inhibitors can be prescribed by a primary care provider (PCP), but if PDE-5 inhibition is not successful, patients should be referred to specialized program that addresses the physical and psychosocial aspects of ED, offering not only more options for ED but also alternatives to penetrative intercourse to maintain intimacy.

●Dry ejaculation – Prostate cancer survivors should be warned that they may experience lack of ejaculation (anejaculation, or "dry" ejaculation) at the point of orgasm. While this is an immediate side effect after surgery, it may occur later over several years after RT [44,45]. Clinicians and patients should be aware that treatments for ED will have no impact on dry ejaculation. (See "Treatment of male sexual dysfunction", section on 'Ejaculatory disorders'.)

●Change in orgasmic quality and climacturia – Changes in orgasmic quality include anorgasmia, decreased intensity of orgasm, painful orgasm (dysorgasmia), rarely a more intense orgasm [46], and climacturia (urinary leakage associated with arousal and orgasm). Climacturia can occur after RP, usually in the first year following treatment [47-50], and it is also reported in males undergoing definitive RT for prostate cancer [48,51].

Dysorgasmia may improve after 24 months and can be treated with tamsulosin with some benefit [52]. Although limited evidence exists to address climacturia, conservative treatment is usually attempted initially. Pelvic floor strengthening to treat urinary incontinence may be beneficial and self-management strategies such as bladder emptying prior to sexual activity, use of a constriction loop to compress the urethra, or a condom to catch the urine may be useful in selected cases [53,54]. Surgical success with a male sling or artificial urinary sphincter mirrors that for stress urinary incontinence surgery in general. (See "Urinary incontinence after prostate treatment", section on 'Sexual arousal incontinence and climacturia'.)

●Penile shortening and curvature – End-organ, microvascular, and hypoxic damage following prostate cancer treatment may lead to corporal fibrosis, collagen deposition, and penile shortening or curvature [55]. These changes tend to occur early after surgery and may persist among long-term survivors [56-58].

Limited data on penile changes after RT are available, but penile curvature or Peyronie's disease can occur after either RP or RT [51,59]. Affected patients who wish to pursue treatment for Peyronie's disease should be referred to a urologist who specializes in treating this condition. (See "Peyronie's disease: Diagnosis and medical management" and "Surgical management of Peyronie's disease".)

Urinary dysfunction

●Incontinence – Urinary incontinence after surgery is usually at its worst immediately after the urinary catheter is removed and tends to improve over time during the first year or two postoperatively (table 5). If urinary incontinence occurs after RT, it is usually a late occurrence. (See "Urinary incontinence after prostate treatment", section on 'Rates of incontinence' and "Urinary incontinence after prostate treatment", section on 'Risk factors for incontinence'.)

Referral to a physical therapist with expertise in male pelvic floor strengthening may improve both continence and quality of life after RP [60]; though short-term improvements have been variable. Residual stress incontinence is not uncommon and may necessitate use of a protective pad. Patients who have moderate to severe urinary incontinence should be referred to a urologist for evaluation and possible treatment that might include placement of an artificial urinary sphincter or urinary sling [2]. Guidelines for evaluation and management of urinary incontinence after prostate treatment are available from the American Urological Association [61]. This subject is discussed in detail elsewhere. (See "Urinary incontinence after prostate treatment".)

●Hematuria and other urinary symptoms – Irritative bladder symptoms including urgency, frequency, and dysuria occur in up to 50 percent of males during RT for prostate cancer, and while they usually clear within four weeks, they can persist in a small number of men. Alpha blockers such as tamsulosin or terazosin may ameliorate irritative bladder symptoms [62]. Anticholinergic agents that target muscarinic receptors in the bladder such as oxybutynin or trospium reduce the contractility of the detrusor muscle but can also cause dry mouth. (See "External beam radiation therapy for localized prostate cancer", section on 'Urinary symptoms'.)

Hematuria, like rectal bleeding after RT, may be due to small vessel damage, but hemorrhagic cystitis is also a possibility and cystoscopic evaluation is warranted to rule out a urothelial or other malignancy. (See "External beam radiation therapy for localized prostate cancer", section on 'Urinary symptoms' and "Chemotherapy and radiation-related hemorrhagic cystitis in cancer patients", section on 'Radiation therapy'.)

Urethral stricture may occur as a long-term consequence of surgery and/or RT, causing urinary symptoms such as decreased urinary stream and urinary retention. These patients should be referred for urologic evaluation with flow studies and possible urethral dilatation or other interventions. (See "Strictures of the adult male urethra".)

Bowel dysfunction and gastrointestinal bleeding — Among males treated for localized prostate cancer, bowel problems are much more common after RT than after RP [63]. Pelvic RT for prostate cancer may be associated with both early and late gastrointestinal toxicity (see "Overview of gastrointestinal toxicity of radiation therapy" and "Radiation proctitis: Clinical manifestations, diagnosis, and management" and "Diagnosis and management of chronic radiation enteritis"):

●Acute side effects include proctitis or enteritis. The reported incidence of acute radiation proctitis ranges from 5 to 30 percent depending on the definition used, the dose of radiation, and the treatment volume. Symptoms usually resolve within three to eight weeks of completing therapy. Addition of fiber to the diet and the use of antidiarrheals are effective. In addition, patients should be counseled on the importance of hydration. Use of hydrocortisone suppositories or foam may also be useful [63]. (See "Radiation proctitis: Clinical manifestations, diagnosis, and management", section on 'Management'.)

●Late or long-term gastrointestinal side effects occur in up to one-quarter of patients after RT [64], but the incidence of severe (grade 3 or worse) toxicity in males treated with high doses of RT is low, only approximately 1 to 5 percent. Symptoms may include frequent, loose stools, rectal mucous discharge, rectal urgency (tenesmus), rectal bleeding, ulcer, and fistula. These symptoms can continue to affect activities of daily living even five years after the completion of therapy [65,66]. (See "External beam radiation therapy for localized prostate cancer", section on 'Gastrointestinal'.)

Management of chronic radiation enteritis may include dietary modification, antidiarrheal agents, and bile acid sequestrants. In general, surgery for radiation enteritis is avoided, if possible, because of several inherent difficulties in operating on patients with chronic radiation injury. (See "Diagnosis and management of chronic radiation enteritis", section on 'Approach to management'.)

Patients who experience long-term rectal bleeding should be referred to a gastroenterologist for further workup. While rectal bleeding may be secondary to postradiation telangiectasias, other causes of bleeding (including colorectal cancer) should be ruled out [66]. (See "Diagnosis and management of chronic radiation enteritis", section on 'Differential diagnosis' and "Radiation proctitis: Clinical manifestations, diagnosis, and management", section on 'Differential diagnosis'.)

Side effects of traditional ADT

Definition and general issues — The term "traditional" androgen deprivation therapy (ADT) refers to medical or surgical treatments that lower testosterone to "castrate" levels (<50 ng/dL). These include gonadotropin releasing hormone (GnRH) antagonists and agonists, and surgical castration. (See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer", section on 'Introduction'.)

As noted above, many males who are treated for prostate cancer will be receiving ADT, either short-term (eg, concurrent with definitive RT, or in the adjuvant or early salvage setting), or long-term for advanced disease. (See 'Overview of prostate cancer treatment options' above.)

Males who are receiving ADT are generally followed by their genitourinary oncology specialist (urologist, radiation, and/or medical oncologist). However, given the breadth of possible side effects of ADT, it is important for PCPs to be aware of the potential impact of ADT on underlying comorbidities they are treating.

Many of the acute and chronic side effects of ADT are due to castrate levels of testosterone. Those prescribing ADT often mention the side effects of hot flashes, lack of libido, and ED in conversation with the patient. However, there are numerous other possible side effects about which patients should be informed before ADT is started.

In general, the side effects associated with short-term ADT resolve over time once treatment is discontinued, although recovery may be slow. However, for many men, especially those with advanced disease, continuous ADT is advised, and side effects will continue for as long as treatment continues because testosterone levels continue to be suppressed. In some cases, periods of time when males are off therapy (so-called intermittent as compared with continuous androgen deprivation) may be associated with decreases in these side effects, especially those associated with physical and sexual function, thereby improving quality of life. Given that phase III trials have demonstrated survival benefit for continuous ADT plus either chemotherapy or an androgen receptor inhibitor, intermittent ADT is not generally used in males with overt metastatic prostate cancer. However, it may be a reasonable alternative for males with biochemical recurrence as the only evidence of recurrence after definitive local therapy. This subject is discussed in more detail elsewhere. (See "Initial systemic therapy for advanced, recurrent, and metastatic noncastrate (castration-sensitive) prostate cancer", section on 'Intermittent versus continuous ADT'.)

For most males embarking on a course of either short-term or long-term ADT, it is good practice to make a referral to a dietician to review healthy eating habits to prevent or minimize weight gain, and to recommend optimal calcium and vitamin D intake. Similarly, referral to an exercise physiologist and/or physical therapist for instruction in an exercise routine that will help maintain muscle mass and bone mineral density as well as minimize weight gain and other undesired side effects of ADT is advised. (See 'Issues specific to prostate cancer survivors' above.)

There are numerous educational materials or websites available to help patients learn about the side effects of ADT and how to mitigate them, including Prostate Cancer UK [67], Prostate Cancer Supportive Care Program [68], or a workbook by Wassersug et al [69].

Overview of specific major side effects

●Effects on glucose metabolism – Patients treated with ADT for prostate cancer may have complications related to dysregulated glucose metabolism. These include the onset of decreased insulin sensitivity, a higher risk for diabetes mellitus, and/or worsening of diabetic control in patients with pre-existing disease. (See "Side effects of androgen deprivation therapy", section on 'Body composition and metabolism'.)

●Cardiovascular effects – The most common noncancer-related cause of death among prostate cancer survivors is cardiovascular disease (CVD) [70]. There are conflicting results regarding the impact of long-term ADT on CVD risk, but none of the trials (until recently) were designed to specifically answer that question. However, taken together, the majority of studies, mainly observational, suggest that ADT increases cardiovascular morbidity and/or mortality, especially in those with pre-existing CVD. Cardiac events often occur early, within the first six months after initiation of ADT. This may be due to the adverse effects of ADT on traditional cardiovascular risk factors, including lipoproteins, insulin sensitivity, and obesity.

Whether or not ADT increases the cardiovascular toxicity for all patients receiving ADT is unknown; however, the risks are sufficient to support counseling and appropriate risk reduction measures for all males initiating ADT [71]. The potential benefits of ADT when used for appropriate indications in prostate cancer must always be weighed against the potential risks of toxicity, especially of cardiovascular events. This subject is discussed in detail elsewhere (see "Side effects of androgen deprivation therapy", section on 'Potential cardiovascular harm'). A particular area of uncertainty is the relative cardiovascular toxicity of GnRH antagonists versus agonists. GnRH agonists (eg, leuprolide) are by far the most commonly used form of medical castration while GnRH antagonists (degarelix, and the oral agent relugolix) are used infrequently despite the fact that some data suggest that there may be less cardiovascular toxicity with GnRH antagonists as compared with agonists. However, the choice of a GnRH agonist or antagonist may not be as important if aggressive risk-reduction cardiology care is provided to males with known CVD who are about to start ADT:

•In the phase III HERO trial comparing leuprolide with relugolix, there were fewer cardiovascular adverse events with relugolix, but these events were not adjudicated study endpoints [72].

•On the other hand, the PRONOUNCE trial, a phase III trial of males with pre-existing CVD comparing adjudicated major adverse cardiac events after degarelix or leuprolide failed to show a lower cardiovascular risk profile with degarelix compared with leuprolide, all patients on the study were required to have their cardiac care optimized by a cardiologist prior to and during the trial, and this may have resulted in the lower rates of observed versus anticipated cardiovascular events in the leuprolide arm [73].

This subject is discussed in detail elsewhere. (See "Initial systemic therapy for advanced, recurrent, and metastatic noncastrate (castration-sensitive) prostate cancer", section on 'GnRH antagonists'.)

A simple screening tool called STAMP identifies males at highest risk of CVD by asking if the patient has had a diagnosis of Stroke; Transient ischemic attack; Abdominal aortic aneurysm or other aortic disease; Myocardial infarction, angina, or previous revascularization; or Peripheral vascular disease. [74]. If an individual has any of these conditions, he should be considered at risk for an adverse cardiovascular event during ADT.

Males starting on ADT, especially those at high risk, should be followed and managed by a multidisciplinary team and treated according to best practices including:

•If lipids are abnormal, use statin therapy to lower low-density lipoprotein cholesterol. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)

•If blood pressure exceeds goal based on cardiovascular risk, add antihypertensive therapy. (See "Goal blood pressure in adults with hypertension".)

•If fasting glucose is elevated and hemoglobin A1c is abnormal, approaches to lowering glucose are appropriate. (See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults", section on 'Diagnostic tests'.)

•Patients with known CVD should take aspirin (generally 81 mg/day) unless contraindicated. (See "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)

•Males who continue to smoke should be referred to smoking cessation programs. (See "Overview of smoking cessation management in adults".)

●Venous and arterial thromboembolic effects – It is well known that there is an increased risk for deep vein thrombosis, pulmonary embolism, and arterial emboli in males with metastatic prostate cancer who are treated with ADT. However, there is also evidence that even males with localized cancer treated with ADT may have an increased risk of thromboembolic events. (See "Side effects of androgen deprivation therapy", section on 'Thromboembolic events'.)

As such, clinicians should include a history of hormonal therapy for prostate cancer in any assessment for thromboembolism. (See "Overview of the causes of venous thrombosis", section on 'Acquired risk factors' and "Risk and prevention of venous thromboembolism in adults with cancer" and "Epidemiology and pathogenesis of acute pulmonary embolism in adults", section on 'Risk factors'.)

●Anemia – After starting ADT, it is common to see a drop in hemoglobin/hematocrit due to the impact of castrate levels of testosterone on endogenous erythropoietin. This is usually only mild to moderate with normochromic, normocytic indices. However, if anemia develops after starting ADT and the patient has not had routine colon cancer screening, a colonoscopy may be warranted. (See "Side effects of androgen deprivation therapy", section on 'Anemia'.)

●Bone health

•ADT-related bone loss – Androgen deprivation therapy (ADT) increases bone turnover, decreases bone mineral density (BMD), and increases the risk of bone fractures in males with prostate cancer. Loss of BMD can be detected after six to nine months of ADT, and longer therapy confers a higher risk. Osteoporotic skeletal fractures occur in up to 20 percent of males within five years of starting ADT. Bone health may be affected by ADT even after discontinuation, including an increased risk of osteoporosis and a higher risk of vertebral and hip fractures. (See "Side effects of androgen deprivation therapy", section on 'Osteoporosis and bone fractures'.)

Other factors contributing to osteoporosis include reduced intake of calcium, low vitamin D levels, alcohol abuse, smoking, and chronic use of corticosteroids. In addition, pelvic RT has been associated with a higher risk of pelvic fractures [75-77].

Males receiving ADT should be counseled to add dietary calcium intake (food and supplements) 1000 to 1200 mg daily and supplemental vitamin D 800 to 1000 international units daily. Beneficial lifestyle modifications include smoking cessation, moderating alcohol and caffeine consumption, vitamin D and calcium supplementation, and regular weight bearing or resistance exercises. (See "Side effects of androgen deprivation therapy", section on 'Preventive strategies'.)

For all males starting ADT who do not have bone metastases, a pretreatment dual-energy x-ray absorptiometry (DXA) scan should be done to establish baseline BMD. For males receiving continuous ADT, a follow-up DXA scan is typically done 12 to 24 months after starting ADT, depending on the baseline value, to re-evaluate BMD and the presence of osteopenia or osteoporosis. (See "Side effects of androgen deprivation therapy", section on 'Assessment of bone density'.)

Males who are found to have osteopenia or osteoporosis on a DXA scan and who are going to continue on ADT should be treated with an osteoclast inhibitor. (See "Side effects of androgen deprivation therapy", section on 'Preventive strategies'.)

Patients with poor dental hygiene are at increased risk for medication-related osteonecrosis of the jaw. Prior to starting an osteoclast inhibitor, all patients should have clearance from their dentist attesting to good dental hygiene, and any needed invasive dental work should be completed prior to starting treatment. (See "Medication-related osteonecrosis of the jaw in patients with cancer", section on 'Prevention'.)

•Males with bone metastases – For males with bone metastases, zoledronic acid and denosumab are also used but at different doses and schedules for the purpose of preventing skeletal complications, irrespective of the presence of osteopenia or osteoporosis. This subject is discussed in detail elsewhere. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors".)

●Body composition and body image

•Weight gain – Self-image is central to self-confidence and sexual performance. Obesity (body mass index [BMI] >30 kg/m²) is prevalent at the time of diagnosis of prostate cancer (26 percent in one study [78]) and it is associated with higher cardiovascular and all-cause mortality. While obesity may be a pre-existing condition, many males gain an average of 10 pounds within one year of starting ADT [79]. The weight gain is typically due to an increase in body fat in the waist, hips, and thighs. In order to minimize weight gain or achieve weight loss, referral to a dietician is suggested in males receiving continuous ADT to review healthy eating habits and snacking strategies. The importance of adequate exercise in addition to dietary changes is discussed in detail above and elsewhere. (See 'Issues specific to prostate cancer survivors' above and "Side effects of androgen deprivation therapy", section on 'Role of structured exercise'.)

•Decreased muscle mass – ADT can lead to a decrease in muscle mass and strength, especially in the large muscles in the thighs and upper arms. The loss in muscle mass accentuates the increase in body fat mentioned above. Resistance exercises can play a significant role in minimizing muscle loss and should be encouraged [80]. (See 'Issues specific to prostate cancer survivors' above and "Side effects of androgen deprivation therapy", section on 'Role of structured exercise'.)

•Gynecomastia – Enlargement and tenderness of breast tissue can occur in a significant proportion of males on ADT and does not regress if ADT is stopped. Prophylactic electron beam RT may lessen breast enlargement but may not prevent it completely and is not a treatment for breast enlargement once it occurs. Gynecomastia can be treated with subcutaneous mastectomy if desired. (See "Management of gynecomastia", section on 'Men with prostate cancer'.)

•Thinning or loss of body hair – ADT commonly causes thinning or loss of all male body and facial hair. This can be especially distressing if the patient does not expect this as a side effect. It is usually reversible if ADT can be stopped. Interestingly, scalp hair may actually increase in response to ADT. (See "Side effects of androgen deprivation therapy", section on 'Thinning of body hair'.)

•Penile shortening and shrinking of testicles – Penile shortening may already exist after primary treatment. (See 'Sexual dysfunction' above.)

However, further retraction of the penis and testicular atrophy may occur with ADT and the patient should be forewarned of these possibilities. These effects may or may not be reversible, depending on patient-specific factors such as age, prior therapies, etc. (See "Side effects of androgen deprivation therapy", section on 'Decreased penile and testicular size'.)

●Neurocognitive and psychologic effects

•Loss of libido – While the majority of males report diminution or total lack of sex drive on ADT, it is not universal; sexual activity is not solely driven by libido and in some men, libido can be maintained while on ADT [81]. If it happens, loss of libido in males receiving ADT usually develops within the first several months, and ED follows [82]. Sexual dysfunction should be anticipated and couples counseled before ADT is started. A sex therapist may be helpful in addressing these issues with a couple before they become problems. (See 'Sexual dysfunction' above.)

•Vasomotor symptoms – Vasomotor symptoms commonly occur in males on ADT, but the frequency and intensity is quite variable and they may be triggered by emotional stimuli or physical heat. (See "Side effects of androgen deprivation therapy", section on 'Vasomotor symptoms'.)

The success of various agents for treatment of vasomotor symptoms in males ranges widely, and benefits must often be balanced against treatment-related side effects. The available evidence suggests that the pharmacologic approach to the management of hot flashes in males being treated with ADT is similar to that in women. (See "Menopausal hot flashes".)

Potentially effective agents include serotonin reuptake inhibitors, progestational agents, cyproterone, selective serotonin uptake inhibitors, and gabapentin. Although megestrol acetate can successfully treat vasomotor symptoms, it should be used with caution as its use has been reported to cause rapid progression of prostate cancer [83,84]. (See "Side effects of androgen deprivation therapy", section on 'Medications'.)

•Fatigue and lack of energy – Fatigue is a very common symptom in males with prostate cancer. Fatigue or lack of energy is a highly prevalent and often annoying side effect of ADT but it also occurs in patients treated with primary local therapy without ADT [85], and may be chronic in these cases [86-89]. Among males receiving ADT, the relationship between anemia and fatigue symptoms is unclear. The treatment approach for fatigue mirrors that for other cancer survivors who complain of fatigue and includes exercise. (See "Cancer-related fatigue: Treatment" and "Side effects of androgen deprivation therapy", section on 'Fatigue'.)

•Depression and anxiety – Depression and anxiety are prevalent in males with prostate cancer, and suicidal ideation is not uncommon [90,91]. The use of ADT can exacerbate depression and anxiety, especially in males with a history of a depressive disorder in the past. Contributing factors include dealing with sexual and urinary side effects, changes in body image, fear of recurrence or disease progression (which may persist even many years after diagnosis and treatment [92]) loss of autonomy, and poor-quality sleep. Males who have a history of depression in the past may benefit from closer follow-up by a PCP or a therapist for signs of early depression. (See "Side effects of androgen deprivation therapy", section on 'Emotional and cognitive changes'.)

•Emotional lability – While emotional lability or irritability may be a component of depression, it can also occur independently of depression [93]. For example, males often describe crying in response to emotional stimuli that would not have caused tearfulness prior to starting ADT. Partners often describe having a "short fuse," which can be disconcerting and interfere with the couple's relationship if this possibility is not raised before starting ADT. (See "Side effects of androgen deprivation therapy", section on 'Emotional and cognitive changes'.)

•Difficulty sleeping – The reasons for difficulty sleeping have not been identified, but nocturnal vasomotor symptoms may contribute. Exercise and use of medications to treat vasomotor symptoms may improve sleep. (See "Side effects of androgen deprivation therapy", section on 'Vasomotor symptoms'.)

•Cognitive effects – There is some evidence to suggest a link between ADT and cognitive dysfunction, including Alzheimer's disease and other forms of dementia; however, it is inconsistent and nonspecific. At least some data support the view that advanced age, comorbidity, and advanced disease stage may account for much of the cognitive disorders seen in these men, and that cognitive dysfunction may have preceded the diagnosis of prostate cancer. However, others note an elevated risk for cognitive dysfunction even after adjusting for factors such as age and comorbidity. Few prospective studies have been done in which baseline cognitive function is measured and compared with that on ADT at various time points [94]. A consistent finding in these studies is an effect of ADT on spatial memory. Functional brain imaging pre- and post-ADT demonstrates changes in regional brain metabolism associated with mood, verbal memory, and spatial performance [95].

Despite these controversies, updated year 2019 guidelines for management of prostate cancer in older patients from the International Society of Geriatric Oncology suggest that clinicians discuss the risk of cognitive dysfunction with older males with prostate cancer who are considering use of ADT [96]. For individuals with pre-existing cognitive deficits, the benefits of ADT should be weighed against the possible harms. This subject is discussed in detail separately. (See "Side effects of androgen deprivation therapy", section on 'Emotional and cognitive changes'.)

Preliminary data suggest that a workshop format skills training intervention can improve cognition and reduce cognitive dysfunction symptoms in cancer survivors, including males receiving ADT for prostate cancer [97]. Exercise may also improve cognitive function in this setting. (See "Side effects of androgen deprivation therapy", section on 'Role of structured exercise'.)

Side effects of novel hormonal therapies — There are two classes of "novel hormonal therapy" agents that target the androgen pathway in a manner that is different from conventional ADT, and are increasingly used, either with or without ADT for treatment of all stages of prostate cancer. The second-generation antiandrogens that block the androgen receptor (androgen receptor antagonists) include enzalutamide, apalutamide, and darolutamide. Androgen synthesis inhibitors are CYP17 inhibitors that block the production of androgens in the adrenal gland and prostate cancer cells and includes abiraterone acetate and fine particle abiraterone. When given in combination with ADT, these novel hormonal therapies increase the risk of cardiovascular toxicity, hypertension, fractures, and falls compared with ADT alone [98-102]. Thus, males taking these drugs require additional scrutiny. (See "Castration-resistant prostate cancer: Treatments targeting the androgen pathway".)

HYPOGONADISM AND TESTOSTERONE REPLACEMENT — For males who have symptomatic hypogonadism and a history of prostate cancer, the use of testosterone replacement therapy (TRT) is controversial. While there are at least theoretical concerns that testosterone may stimulate cancer growth, high-quality clinical data to support this fear are generally lacking. In our view, shared decision making that considers individual disease characteristics and the values and preferences of the patient is appropriate for males previously treated for localized disease who have symptomatic hypogonadism. As an example, a man who was treated for localized prostate cancer in the past and has an undetectable prostate-specific antigen (PSA) may decide that the potential benefits of TRT outweigh the risks. On the other hand, a man who is pursuing active surveillance (AS) and who is anxious about the potential for disease progression over time may decide that the theoretical risks of TRT outweigh the benefits. In general, for males with advanced/metastatic disease who are receiving androgen deprivation therapy (ADT), we suggest not pursuing TRT; the goal of ADT in these patients is to achieve castrate levels of serum testosterone.

This approach is consistent with 2018 AUA guidelines [103,104] which state that until there is definitive evidence demonstrating testosterone is not safe for use in prostate cancer patients the decision to commence testosterone therapy for a hypogonadal man with a history of prostate cancer should be a negotiated decision based on the perceived potential benefit of treatment. Males who have had definitive treatment for localized disease who are considering TRT should have an undetectable PSA level beforehand.

Testosterone deficiency, which is defined as a serum testosterone level <300 nm/dL, can be associated with symptoms of male hypogonadism, including low energy, fatigue, decreased strength, loss of muscle mass, central obesity, irritability, depression, erectile dysfunction, and low sex drive. (See "Clinical features and diagnosis of male hypogonadism".)

TRT is an effective treatment for male hypogonadism, but its use in males with a history of prostate cancer is controversial due to the androgen sensitivity of prostate cancer cells, and at least theoretical concerns for stimulating disease progression [105]. While there are no prospective placebo-controlled randomized trials addressing this issue, several uncontrolled studies [106-108] and a meta-analysis of 22 individual reports totaling 1084 patients with a history of TRT after definitive local therapy of localized prostate cancer have all concluded that TRT appears safe and was not associated with an increased risk of biochemical recurrence [107]. Although there are fewer data in males undergoing AS, and follow-up is generally short, there are no reports documenting biopsy grade progression or rising PSA in males who receive TRT while undergoing AS [109-111].

For hypogonadal males with a history of prostate cancer who decide to initiate TRT, current guidelines recommend following PSA levels at least on the same schedule as males with prostate cancer without testosterone deficiency, initially at three months, then at six month intervals [103,104,112]. However, there is evidence that PSA testing rates in clinical practice are inexplicably low in this setting [113].

A general discussion of diagnosing and treating male hypogonadism is provided separately. (See "Testosterone treatment of male hypogonadism".)

CAREGIVER DISTRESS — Partners often assist with treatment decisions, help maintain quality of life, and provide emotional support, but this can be at significant cost to the caregiver. In addition, the side effects of treatment (eg, urinary incontinence, sexual dysfunction) and changes in disease state may cause stress in the relationship [114-116]. Thus, the partners of males treated for prostate cancer may report greater emotional distress than the males themselves [115]. Therefore, biopsychosocial support for patients and partners may be warranted, even among long-term couples [117,118]. Evaluation for caregiver distress can be assessed with the Brief Zarit Caregiver Burden Interview [119,120]. (See "Palliative care delivery in the home", section on 'Burden of caregiving'.)

MONITORING FOR RECURRENCE AND/OR DISEASE PROGRESSION

Localized disease — Serial evaluation of serum prostate-specific antigen (PSA) is the mainstay of surveillance testing in males who have undergone definitive therapy for localized prostate cancer. Serum PSA is typically monitored every 6 to 12 months for the first five years and annually thereafter. Imaging studies, such as bone scan, transrectal ultrasound, multiparametric prostate magnetic resonance imaging, computed tomography (CT), and positron emission tomography (PET) scanning have no role as screening tests for recurrence of localized prostate cancer in the absence of a rising serum PSA or specific symptoms. (See "Follow-up surveillance after definitive local treatment for prostate cancer".)

Approximately 30 to 50 percent of patients who have been treated with definitive therapy will eventually relapse [121]:

●The most common form of relapse is a "biochemical” recurrence, defined as a rising PSA without evidence for metastatic disease on conventional imaging studies (ie, radionuclide bone scan, contrast-enhanced CT), although most patients do have micrometastatic disease. (See "Rising serum PSA following local therapy for prostate cancer: Definition, natural history, and risk stratification".)

In the United States, more sensitive prostate-specific PET tracers (such as F-18 fluciclovine and novel radiotracers that target the prostate-specific membrane antigen [PSMA; such as gallium-68 and F-18 PSMA]) have been approved to detect suspected recurrent prostate cancer that is not imaged by conventional imaging. However, there is no consensus as to the appropriate timing for these next generation imaging techniques or sequence of diagnostic imaging in the setting of a rising PSA after definitive local therapy. This subject is discussed in detail elsewhere. (See "Rising serum PSA following local therapy for prostate cancer: Diagnostic evaluation".)

●A small proportion of males with recurrence in the prostate bed or regional nodes after prostatectomy may be cured with salvage RT. In this setting, to optimize the opportunity for cure, radiation should be given at the lowest possible PSA value, so patients should be referred expeditiously to a radiation oncologist for evaluation. (See "Rising or persistently elevated serum PSA following radical prostatectomy for prostate cancer: Management".)

●Relapsing with metastatic disease is less common but can occur in a man who was not followed with serial post-treatment PSA testing. Late recurrences (>5 years) are not common but have been reported as late as 10 to 15 years after therapy [122]. For most males with metastatic castration sensitive prostate cancer, the treatment is continuous androgen deprivation therapy with or without another systemic agent (eg, docetaxel, abiraterone, enzalutamide or apalutamide), although some males may benefit from local treatments to the prostate bed or metastasis-directed local therapy. (See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer".)

Advanced disease — For males with castration-sensitive prostate cancer who are undergoing systemic therapy, periodic assessment should be geared toward identifying signs and symptoms of disease progression, as well as the side effects of treatment. (See 'Side effects of traditional ADT' above.)

As with earlier stage disease, serial evaluation of serum PSA is the mainstay of testing. Consensus-based guidelines from the National Comprehensive Cancer Network recommend testing PSA every three to six months during treatment for advanced prostate cancer [123]. Most clinicians make decisions about the need for radiographic evaluation based on changes in PSA values and/or the development of new symptoms. Therapeutic changes are usually not made based on a rising PSA alone. (See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer", section on 'Assessment during treatment'.)

If PSA levels do not fall in response to therapy or subsequently rise, the adequacy of testosterone suppression should be checked. Many clinicians routinely check serum testosterone levels every three months to ensure that they remain in the castrate range (<50 ng/dL).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of prostate cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Prostate cancer (The Basics)" and "Patient education: Choosing treatment for low-risk localized prostate cancer (The Basics)")

●Beyond the Basics topics (see "Patient education: Treatment for advanced prostate cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●General approach – Following treatment, prostate cancer survivors require assessment for treatment-related sequelae and disease progression, in addition to routine preventive and general health care. Cancer specialists (urologists and medical and/or radiation oncologists) and primary care providers (PCPs) should clearly communicate who will take responsibility for the different aspects of post-treatment surveillance to avoid duplication of effort. (See 'Coordination of follow-up care' above.)

The general principles guiding follow-up of prostate cancer survivors include:

•Appropriate testing to monitor for disease progression and/or recurrence.

•Periodic quality of life surveillance, which should be done using a validated one page instrument that addresses urinary, sexual, bowel, and vitality domains (eg, Expanded Prostate Cancer Index Composite for Clinical Practice [EPIC-CP]).

•Assessment for potential treatment-related sequelae. This should include regular, ongoing evaluation for sexual dysfunction, including partner evaluation, if the patient has a partner, and referral to a sexual health clinician if warranted. Recommendations for screening and assessment for sexual dysfunction in male cancer survivors are provided separately. (See "Overview of sexual dysfunction in male cancer survivors", section on 'Sexual health questionnaires'.)

•Encouraging a healthy lifestyle (diet, exercise, alcohol consumption, smoking cessation).

●Treatment-related sequelae

•Prominent concern of prostate cancer survivors is sexual function and its relationship to body image, self-esteem, and masculinity. In most cases, sexual function is likely to be permanently altered after any form of treatment for prostate cancer. (See 'Sexual dysfunction' above.)

•Among males treated for localized prostate cancer, post-prostatectomy urinary incontinence is usually worst immediately after surgery and tends to improve over time during the first year or two (table 5). If urinary incontinence occurs after radiation therapy (RT), it is usually a late occurrence. (See 'Urinary dysfunction' above.)

Bowel problems (proctitis, enteritis, bleeding, rectal urgency) are much more common after RT than after prostatectomy. Pelvic RT may be associated with both early and late gastrointestinal toxicity. (See 'Bowel dysfunction and gastrointestinal bleeding' above.)

•Many males who are treated for prostate cancer will be receiving androgen deprivation therapy (ADT), either short term during treatment for localized disease, or long-term for advanced disease. (See 'Overview of prostate cancer treatment options' above.)

Males who are receiving ADT are generally followed by their oncology specialist (urologist, radiation, and/or medical oncologist), but PCPs should understand the range of possible side effects and the potential impact of ADT on underlying comorbidities. The many side effects of ADT can often be successfully mitigated with a variety of approaches; engaging in regular exercise ameliorates more ADT side effects than any other treatment. (See 'Overview of specific major side effects' above.)

Cardiovascular disease (CVD) is more common in males with prostate cancer and the most common noncancer cause of death in survivors. In males with pre-existing CVD, physicians must ensure adequate cardiology care before initiation of ADT. A simple screening tool called STAMP identifies males at highest risk of CVD by asking if the patient has had a diagnosis of Stroke; Transient ischemic attack; Abdominal aortic aneurysm or other aortic disease; Myocardial infarction, angina, or previous revascularization; or Peripheral vascular disease.

●Testosterone replacement therapy – For males who have symptomatic hypogonadism and a history of prostate cancer, the use of testosterone replacement therapy (TRT) is controversial. While there are at least theoretical concerns that testosterone may stimulate cancer growth, high-quality clinical data to support this fear are lacking. In our view, shared decision making that considers individual disease characteristics and the values and preferences of the patient is appropriate. A man who was treated for localized prostate cancer in the past and has an undetectable prostate-specific antigen (PSA) may decide that the potential benefits of TRT outweigh the risks. On the other hand, a man who is pursuing active surveillance and is anxious about the potential for disease progression over time may decide that the theoretical risks of TRT outweigh the benefits. In general, for males with advanced/metastatic disease who are receiving ADT, we suggest not pursuing TRT (Grade 2C); the goal of ADT in these patents is to achieve castrate levels of serum testosterone. (See 'Hypogonadism and testosterone replacement' above.)

●Post-treatment cancer surveillance – Serial evaluation of serum PSA is the mainstay of surveillance testing in males who have undergone definitive therapy for localized prostate cancer and for those with more advanced disease. For males treated for localized disease, imaging studies, such as bone scan, transrectal ultrasound, prostate magnetic resonance imaging, computed tomography, and positron emission tomography scanning have no role as screening tests for recurrence in the absence of a rising serum PSA or specific symptoms. Specific recommendations are provided separately. (See "Follow-up surveillance after definitive local treatment for prostate cancer".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Ted A Skolarus, MD, MPH, FACS, who contributed to an earlier version of this topic review.

We are saddened by the death of Nicholas Vogelzang, MD, who passed away in September 2022. UpToDate gratefully acknowledges Dr. Vogelzang's role as Section Editor on this topic, and his dedicated and longstanding involvement with the UpToDate program.