Prostate Cancer

on
think of cancer as flower to kill flower with radiation you would want it to be wilted. 
hormone injections can be used wilt away hormones
however, if you do surgery before hormones you will have a cleaner cut


Hormone deprivation therapy can cause men hot flashes, cry less muscle mass more fat

Concept surgery more up front costs - impotence, trouble urinating, sexual dysfunction however, recovers better for younger
If you do radiation first then tissue will be harder to do surgery
Radiation - Friable tissue that will never recover. worse for younger people. Friable tissue - like after a fire there is dead trees. tissues become changed can't recover fibrosis bladder elasticity issues
Free PSA levels are lower in Prostate cancer than in normal prostate tissue or benign disease.

Free PSA:total PSA ratio

The percentage of free prostate specific antigen (PSA) compared to total PSA. Used to assess the risk of prostate cancer in patients with moderately elevated total PSA levels (i.e., 4.0–10.0 ng/mL). As free PSA levels are low in prostate cancer, a low free PSA:total PSA ratio (< 10–20%) suggests a higher probability of prostate cancer.


prostate 
age, black race, genetic (BRACA 1/2) family history, smoking

Low risk

In termediate / high risk

Diagnosis if PSA doubles





Metastatic / Recurrent
TRUS - transrectal ultrasound
MRI
Biomarkers evaluate for metastases






Finasteride for prostate cancer

PCPT trial 

Urology 

Prostate Cancer 

ERSPC (2009): PSA for prostate cancer screening 

PCPT (2003): Finasteride for prostate cancer prophylaxis 

 

ASCO / AUA 2008 adapted 

The 2003 Prostate Cancer Prevention Trial (PCPT) randomized 18,882 men age ≥55 years to finasteride or placebo for seven years 

 

Does daily finasteride therapy reduce prostate cancer development when compared to placebo? 

Finasteride reduces the incidence of prostate cancer but causes sexual side effects and increases the incidence of high-grade prostate cancer when compared to placebo for primary prevention. 

 

THE PCPT trial showed Finasteride reduces the incidence of prostate cancer but causes sexual side effects and increases the incidence of high-grade prostate cancer when compared to placebo for primary prevention. 

Dysuria, rectal bleeding, impotence, erectile dysfunction

 Prostate Radiation side effects

 Dr. Sam Kumarasena: And the second to last, let’s move on to prostate radiation. What are the acute side effects? We already kind of mentioned that people aren’t really going to see burns with it, so I guess that’s one win! 

Dr. Shreya Trivedi: Yep!

Dr. Daphna Spiegel: A lot of the side effects that you can experience have to do with what’s nearby. And so for a prostate patient I might say, you might find you’re going to the bathroom more frequently, urinating more frequently, sometimes even having more frequent bowel movements or looser stools things like that. 

Dr. Sam Kumarasena: We’re back on that location-dependence theme here! The acute side effects are gonna involve what’s nearby the prostate, the bladder, the rectum, basically anything in the pelvis. Now, how about the late side effects?

Dr. Matthew Abrams: Late side effects. Uh, so things like, um, uh, erectile dysfunction, uh, is a ongoing issue that, uh, can happen after any, um, uh, treatment to the prostate, whether that be surgery or radiation. Sometimes patients, uh, present with, uh, rectal bleeding. That can be associated with the late complication from, from radiation to the prostate. Suffice it to say that if, uh, a patient showed up with prior prostate radiation in your clinic with rectal bleeding, you would absolutely wanna work up that rectal bleeding for any other reason. I would not, um, write it off as related to radiation. That would be almost a diagnosis of exclusion. You would want to rule that up for work that up for, for, you know, as you normally would, um, whether that be, uh, you know, a rectal exam, colonoscopy, et cetera, uh, to make sure you’re not missing any other underlying malignancy, for example.

Dr. Sam Kumarasena: Aye aye, Captain! The diagnosis of exclusion is hammered home yet again. 

Dr. Shreya Trivedi: But, wait a minute, bones are also in the pelvis too, so how does prostate or pelvic radiation affect the bones?

Dr. Daphna Spiegel: Anytime we radiate the pelvis, there’s always the possibility long term that could cause issues with the fracture. Really, it’s true for any bone, but we think about it a lot because obviously you know have really important bones that live in your pelvis. And so we think about that and counsel patients that they may be more likely to develop a hip fracture down the road if they’ve gotten a lot of radiation in this area. 

Dr. Sam Kumarasena: And as a little aside here, I looked into it, to see if there is anything to prevent some of these pelvic fractures and unfortunately, our interventions, things like calcium and vitamin D supplements, or even bisphosphonates, nothings really been shown to be effective in preventing these fractures.

Dr. Shreya Trivedi: Yeah, bummer, it’s surprising given bisphosphonates aren’t, but it’s good to know! So let me try to summarize prostate radiation side effects, big picture ones. Because radiation is often deeper, we are going to see collateral damage to nearby organs, like prostatitis, cystitis and so on. As well as seeing pelvic insufficiency fractures.

Dr. Sam Kumarasena: One last things that came up about prostate radiation side effects, do we see these prostate radiation side effects with all the different types of radiation? This’ll actually be a throwback to part 1, in which we learned that patients with prostate cancer can either get, external beam radiation therapy, OR brachytherapy, with a radioactive source placed at or in the tumor.

Dr. Shreya Trivedi: Yeah so talking to our experts, it turns out BOTH external beam and brachytherapy can produce similar local side effects, think about the cystitis and proctitis that we just talked about. But, because with brachytherapy, the radiation stays closer to the tumor, brachytherapy is going to have a lower risk of affecting organs further away, like the bone. So that means patients getting brachytherapy are going to have a lower risk of pelvic fractures than those getting external beam radiation.


MKSAP

Genitourinary Cancer
Prostate Cancer
Epidemiology and Risk Factors
Adenocarcinoma of the prostate remains one of the most commonly diagnosed types of cancer among men in the United States. Age is a very important risk factor; prostate cancer is rarely diagnosed before age 40 years, but after that point, the incidence increases significantly. Genetics and family history also play an important role in risk. Men with a first-degree relative diagnosed with prostate cancer are twice as likely to be diagnosed. Prostate cancer is also linked with germline mutations in different genes, such as BRCA1 and 2, ATM, CHEK2, HOXB13, and the Lynch syndrome genes, among others.

Diagnosis and Staging
Related Question
Question 30
Prostate cancer is most commonly diagnosed after identification of an elevated serum prostate-specific antigen (PSA) level during screening and in the absence of symptoms. See MKSAP 19 General Internal Medicine 2 for a discussion of current issues relating to prostate cancer screening.

Although urinary symptoms might be present in patients with prostate cancer, they are usually related to benign prostatic hyperplasia. In some men with metastatic disease at the time of initial presentation, bone pain or back pain can be the presenting symptom. If the diagnosis is suspected on the basis of an elevated serum PSA level, the elevation should first be confirmed by a second measurement at least 1 month later. Persistent serum PSA elevation should prompt urology referral, as should an abnormal finding in the prostate on digital rectal examination (DRE).

Prostate biopsy is performed using transrectal ultrasonography for guidance, and several cores should be taken from different regions of the gland. Most commonly, at least five to seven cores are taken per side to provide a sufficient diagnostic yield. Atypical small acinar proliferation and multifocal high-grade prostatic intraepithelial neoplasia are both associated with a high risk of underlying cancer and should prompt rebiopsy.



Risk stratification using serum PSA, Grade Group (based on Gleason score), and TNM cancer staging based on biopsy results and DRE determines prognosis and treatment options (Table 11). Imaging studies need not be done in patients whose risk is very low or low but should be obtained in others to evaluate regional lymph node involvement and metastatic disease. Genetic testing for BRCA gene mutation should be done in all men with high-risk disease, including patients with positive lymph nodes or metastatic disease. The risk of an underlying mutation in patients with metastatic disease is 11.8%.

Key Point
Genetic testing for BRCA gene mutation is recommended for all men with high-risk prostate cancer, including patients with positive lymph nodes or metastatic disease.
Treatment
Related Questions
Question 23
Question 38
Question 68
Treatment options for men with newly diagnosed localized prostate cancer include active surveillance, irradiation, and radical prostatectomy. For men with limited life expectancy or significant medical comorbidities, observation is most appropriate.

Active surveillance is deferral of curative-intent therapy in lieu of regular monitoring for evidence of disease progression. It is an option for men with very-low-risk or low-risk prostate cancer who have a life expectancy of at least 10 years. Active surveillance should consist of DRE (not more than every 12 months), serial measurement of serum PSA (assessing level changes and calculating PSA doubling time), and repeat biopsy. Repeat biopsy is typically done at 1 year, and if no high-grade disease is identified, it can be done less often after that. A PSA doubling time of less than 3 years warrants an additional prostate biopsy. Fifteen-year metastasis-free survival is as high as 97% in appropriately selected patients.

Active treatment of low-risk localized prostate cancer is typically a choice between external beam irradiation and radical prostatectomy. Brachytherapy, in which radioactive implants are inserted into the prostate, is also an option for men with low-risk cancer or selected men with low-volume intermediate-risk cancer.

Irradiation is associated with short-term risks of enteritis (approximately 20% of men) and cystitis (approximately 50% of men). These conditions become long-term complications in a very small percentage of patients. Erectile dysfunction typically increases over time after irradiation, such that by 2 years, approximately 60% to 70% of men have at least moderate erectile dysfunction. However, a recent series found similar rates of decline in men treated with active surveillance.

With radical prostatectomy, the main risks are urinary incontinence and erectile dysfunction. Urinary incontinence is relatively common immediately after surgery. The rate of chronic moderate to severe incontinence is approximately 5% to 10%. Erectile dysfunction is relatively common after surgery and can persist for several years. Approximately 40% of men reported erectile dysfunction 2 years after surgery.

A large study showed no difference in survival after 10 years for patients with localized prostate cancer detected through serum PSA screening who were randomized to receive active surveillance, surgery, or radiation therapy. There was a trend toward improved survival for patients older than 65 years who received either of the active interventions. Patients receiving surgery or irradiation had decreased disease progression and decreased metastatic disease.

For men with intermediate-risk or higher-risk localized disease who are treated with radiation therapy, the addition of a gonadotropin-releasing hormone (GnRH) agonist will delay disease progression. It has also been shown to improve overall survival in men with high-risk and very-high-risk prostate cancer.

After definitive local treatment, men are monitored for evidence of recurrence with serial serum PSA measurements every 3 to 4 months and DRE yearly, although DRE can be omitted if PSA is undetectable. After radical prostatectomy, the PSA should rapidly become undetectable, but after radiation treatment, the PSA will fall gradually and reach a nadir but will not necessarily become undetectable. PSA recurrence after surgery is defined as a detectable PSA level that increases on at least two measurements; after irradiation, PSA recurrence is defined as an increase in the PSA level by at least 2 ng/mL (2 µg/L) above the nadir PSA.

For men with PSA-only recurrence, an evaluation to look for evidence of clinical local or metastatic disease with imaging studies is indicated. If men were treated with initial surgery, and metastatic disease has not been identified, salvage irradiation with or without androgen deprivation therapy (ADT) can be offered. Likewise, if men were treated initially with irradiation, local therapy (such as surgery or cryotherapy) can be offered, provided a transrectal ultrasound–guided biopsy specimen is positive and no metastatic disease is identified. If the result of the specimen is negative, then ADT can be considered. Men with metastatic disease can also be treated with ADT, although the benefit in that setting is uncertain.

ADT results in many short-term and long-term adverse effects. Short-term effects include loss of lean body mass, fatigue, gynecomastia, hair loss, decreased libido, erectile dysfunction, and vasomotor symptoms. Long-term risks include a possible increase in cardiovascular disease, increased risk of venous thromboembolism, and reduction in bone density. All men being treated with ADT should take supplemental calcium and vitamin D, and baseline fracture risk assessment is recommended using a dual-energy x-ray absorptiometry scan, although the impact on outcomes is uncertain.

For men with PSA recurrence, with or without clinical metastatic disease, observation is a reasonable consideration depending on patient and disease-specific factors, such as symptoms and PSA doubling time. This is especially true for men with PSA-only recurrence. For such men with a rapid doubling time (<10 months), treatment is generally recommended; however, men with a slow PSA doubling time (>10 months) do not require immediate treatment because it can take several years for clinical metastatic disease to develop in that setting.

Key Points
Treatment options for men with newly diagnosed localized prostate cancer include active surveillance, irradiation, and radical prostatectomy.
Gonadotropin-releasing hormone agonist therapy is typically administered with radiation therapy for localized intermediate- or high-risk prostate cancer.
Patients with prostate-specific antigen (PSA)–only recurrence of prostate cancer may be treated with androgen deprivation therapy in the presence of a rapid PSA doubling time (<10 months); observation is preferred for patients with slow PSA doubling times (>10 months).
Metastatic Prostate Cancer
Related Question
Question 39
Once distant metastatic disease is diagnosed, the mainstay of therapy is ADT. Options for providing ADT include orchiectomy, GnRH-agonist therapy (with or without antiandrogen), and GnRH-antagonist therapy (Table 12). Psychological aversion to orchiectomy has limited its use in the United States, although it is a rapidly acting and cost-effective way to achieve androgen depletion.

In patients who have clinical metastatic disease, short-term antiandrogen therapy should precede or be started at the same time as a GnRH agonist, and the combination should be continued for at least 7 days because of the risk of a transient worsening of disease-related symptoms, termed a flare reaction. Initial anti-androgen therapy is not necessary if a GnRH antagonist is used. Intermittent ADT is not typically recommended in men with clinical metastatic disease, although it can be offered to mitigate adverse effects. Response can be assessed most easily by serial serum PSA measurement, but imaging also plays a role. The serum testosterone level should be less than 50 ng/dL (1.7 nmol/L) in men treated with ADT.

Men with clinical metastatic disease who respond to ADT are considered to have castrate-sensitive prostate cancer. In this population, ADT can be combined with docetaxel alone or with darolutamide, abiraterone/prednisone alone or with docetaxel, enzalutamide, or apalutamide to improve survival. Irradiation to the primary tumor can also be considered for men with low-volume metastatic M1 disease.

After identifying progressive disease in men being treated with ADT (castrate-resistant prostate cancer), many treatment options exist (see Table 12). Osteoclast inhibitors (bisphosphonates or denosumab) will reduce bone pain and lower fracture risk in men with castrate-resistant, metastatic prostate cancer and should be routinely prescribed. Initial treatment options for castrate-resistant prostate cancer include docetaxel with prednisone, abiraterone with prednisone, enzalutamide and, for symptomatic bone metastases, radium-223. Patients with M0 (without evidence of distant metastasis) castrate-resistant disease do not clearly require treatment. The decision to treat is based on PSA doubling time among other factors. For men with a rapid doubling time, both enzalutamide and apalutamide are effective. For patients who develop progressive disease, a different agent can be used. Cabazitaxel, a chemotherapy agent, can be combined with prednisone for patients who have cancer progression after treatment with docetaxel. Pembrolizumab can be used for select patients characterized by high levels of microsatellite instability or deficient mismatch repair after progression on front-line therapy and absence of an alternative treatment.

Key Points
Continuous androgen deprivation therapy (ADT), including orchiectomy, gonadotropin-releasing hormone–agonist therapy, and gonadotropin-releasing hormone–antagonist therapy, is most appropriate for metastatic prostate cancer.
Men with metastatic prostate cancer who respond to ADT and then receive docetaxel abiraterone/prednisone, enzalutamide, or apalutamide will have improved survival.
All men who are treated with ADT should take supplemental calcium and vitamin D.
Osteoclast inhibitors will reduce bone pain and lower fracture risk in men with castrate-resistant, metastatic prostate cancer.






47 years old and just got mri results back. Not looking good

Just got these results. Being set up with a urologist to discuss next steps. Is this as bad as it looks?

History: Age 47, prostatitis (which report seems to confirm) since my early 20s with really high psa levels which usually dropped after antibiotics. I don't think I have ever had a "normal" PSA result. This is pretty scary to say the least as I am married and have 2 kids under 2 years old.

Is this lesion small? Does the report indicate it has protruded, is bulging or it i unclear? Any advice, insight or words of wisdom would be appreciated.

REPORT:

impression:

  1. multiparametric mri positive for significant or index lesion, intermediate or high grade neoplastic disease.

  2. peripheral zone demonstrates a focal concordant lesion within the lateral and posterolateral aspect of the left prostate base highly concerning for clinically significant disease with findings suggestive of extracapsular extension. seminal vesicles appear uninvolved.

  3. transition zone demonstrates no significant change of bph in a normal size gland.

  4. no osseous lesions or adenopathy appreciated.

  5. tissue sampling recommended.

pi-rads category 5.

1 = very low (clinically significant cancer highly unlikely)

2 = low (clinically significant cancer unlikely)

3 = intermediate (clinically significant cancer equivocal)

4 = high (clinically significant cancer likely)

5 = very high (clinically significant cancer highly likely)

history:

current psa 57.9 ng/ml

prior trus biopsy: none.

comparison study: none

technique: multiparametric mri imaging of the prostate performed on the siemens 3t verio open bore pre and postcontrast. multiplanar high-resolution t2 weighted imaging. t1 dynamic contrast enhancement (dce) during the administration of 10 cc of intravenous vueway. diffusion weighted imaging (dwi). adaptive diffusion coefficient (adc) mapping. three dimensional (3-d) contouring of the prostate with postprocessing on the siemens syngovia independent workstation.

findings:

prostate volume = 23 cc

psa density = 2.5 ng/ml/cc

peripheral zone:

linear and wedge shaped areas of t2 hypointensity throughout the peripheral zone consistent with inflammation/prostatitis.

lesion 1:

- size: 15 x 17 x 17 mm

- location: lateral posterolateral left base, from 3 to 5 o'clock.

concordant abnormality with restricted diffusion, adc values ranging from 320-600 and high signal intensity on 1400 imaging. asymmetrical focal rapid iv contrast enhancement on dce imaging. findings best seen on t2 axial image 18, coronal image 15, sagittal image 21.

extraprostatic tumor extension: there is extracapsular bulge and irregularity at the site of the lesion highly concerning for gross extracapsular extension

- pi-rads: 5, clinically significant cancer highly likely to be present.

transition zone:

no significant changes of bph

no focal concordant transition zone abnormality.

seminal vesicles: seminal vesicles appear uninvolved

urinary bladder: the bladder is predominately decompressed

pelvic lymph nodes: no enlarged or morphologically abnormal lymph nodes.

suspicious bone lesions: none.

other incidental findings: none.


Amboss


Summary

Prostate cancer is one of the most common cancers that affect men, especially those > 50 years of age. Typically, prostate cancer has an indolent course and is usually discovered while still localized in the prostate. This allows many patients to undergo monitoring for progression rather than active treatment, preventing unnecessary treatment-related adverse effects. Prostate cancer is typically diagnosed and monitored using prostate-specific antigen (PSA) testing, multiparametric MRI (mpMRI), and guided biopsy. Once the decision to treat has been made, therapeutic options include radical prostatectomy, radiation therapy, androgen deprivation therapy (ADT), and chemotherapy. Since all treatment options may adversely affect the patient's quality of life, shared decision-making with the patient is strongly encouraged in all current guidelines. Symptomatic management may be preferable in patients with significant comorbidities or limited life expectancy, as further treatment is unlikely to be life-prolonging.

Epidemiology

  • Incidence: following skin cancer (i.e., melanoma and nonmelanoma combined) most common cancer in men in the US  [1]
  • Mortality: in 2020, second leading cause of cancer deaths in men in the US (after lung cancer)
Incidence of cancers in the US (2020 estimates)Cancer mortality in the US (2020 estimates)
Epidemiological data refers to the US, unless otherwise specified.

Risk factors

  • Advanced age (> 50 years)  [1][2]
  • Family history 
  • African-American descent 
  • Genetic disposition (e.g., BRCA2, Lynch syndrome) 
  • Dietary factors: high intake of saturated fat, well-done meats, and calcium
Advanced age is the main risk factor for prostate cancer. Sexual activity and benign prostatic hyperplasia (BPH) are not associated with prostate cancer.
References: [3][4]

Clinical features

Symptoms

Digital rectal examination (DRE) [6][7][8]

A DRE should be performed in individuals with elevated serum PSA levels and as part of the comprehensive evaluation of male LUTS. DRE has a low positive predictive value for detecting prostate cancer and should not be performed as the sole screening modality. 
  • May be normal  in early disease or if the cancer is located in areas of the gland that are not palpable on DRE  [9]
  • Features suggestive of prostate cancer include:
    • Localized indurated nodules on an otherwise smooth surface
    • Prostatomegaly, lobar asymmetry, obliteration of the sulcus
    • Hard nontender nodules 
Most prostate cancers are located in the peripheral zone (posterior lobe) of the prostate. In contrast, BPH occurs in the transitional zone of the prostate.
Even patients with advanced prostate cancer may have a normal DRE; if clinical suspicion is high, continue diagnostic evaluation for prostate cancer!
Urinary bladder (male)

Diagnostics

Approach

The following content is related to diagnosing prostate cancer in symptomatic patients or those with a positive screening test. Screening for prostate cancer in asymptomatic individuals is detailed separately.

Prostate-specific antigen (PSA) levels

PSA is a serine protease produced only in the prostate gland and, therefore, is an organ-specific marker. It is not cancer-specific however, as levels may also be elevated in benign conditions. [10]
  • Indications
  • Interpretation [11][12]
    • Total PSA levels 
      • PSA < 2.5 ng/mL: Prostate cancer is unlikely.
      • PSA 2.5–4 ng/mL: Prostate cancer is possible in symptomatic patients.  [13]
      • PSA > 4 ng/mL: Prostate cancer is likely. [12]
        • PSA 4–10 ng/mL (moderately elevated PSA): ∼ 25% chance of prostate cancer
        • PSA > 10 ng/mL: > 50% chance of prostate cancer
    • Free PSA (unbound) : Free PSA levels are lower in prostate cancer than in normal prostate tissue or benign disease.
  • Other causes of elevated total PSA: BPH, UTI, prostatitis, prostatic trauma or manipulation (including DRE)  [14]
A PSA level ≤ 4 ng/mL does not exclude prostate cancer!
5-alpha reductase inhibitors (5-ARIs) can suppress PSA production, resulting in spuriously low PSA levels. This should be taken into consideration in patients on long-term 5-ARIs (e.g., for BPH). [15][16]
Inflammation, manipulation of the prostate, and other malignant and benign prostate diseases may lead to a false-positive PSA result!

Urinalysis [17][18]

Initial imaging

  • mpMRI of the prostate [19][20]
    • Becoming the preferred imaging modality for suspected prostate cancer  [19][21]
    • Additional indications include:
      • Guidance of prostate biopsy 
      • Clinical suspicion of prostate cancer despite negative transrectal ultrasound (TRUS) or TRUS-guided biopsy
      • Initial staging of confirmed prostate cancer
      • Active surveillance and follow-up
  • Transrectal ultrasound of the prostate: predominantly used to guide prostate biopsy if there is clinical suspicion of prostate cancer  [22][23]
Multiparametric MRI of prostate cancer

Prostate biopsy

  • Indication: clinical suspicion of prostate cancer after shared decision-making with a patient whose life expectancy is ≥ 10 years  [8][24]
  • Important considerations: Consider the following to minimize unnecessary biopsies.  [8]
    • Adjunctive PSA tests
      • Free PSA:total PSA ratio of < 10–20% suggests a high probability of prostate cancer.  [25]
      • PSA density [26]
        • Calculated by dividing total PSA by prostate volume (as determined on imaging)
        • A low PSA density (< 0.08 ng/mL/cc) suggests that clinically significant cancer is unlikely.
    • mpMRI of the prostate (if not already performed)
    • Presence of risk factors for prostate cancer
    • Prostate cancer antigen 3 gene (PCA3) levels in urine [27]
      • The PCA3 gene is expressed more frequently in cancerous tissue than in normal prostate tissue.
      • Increased PCA3 expression in a urine sample taken after DRE  suggests a high probability of prostate cancer.  [7]
  • Technique
  • Findings: adenocarcinoma  [30][31]
    • Gleason grade (Gleason pattern): depending on the degree of differentiation of tumor cells and stromal invasion, tumors are graded from 1 (well-differentiated) to 5 (poorly differentiated)  
    • Gleason score (ranges from 2 to 10): the sum of the two most prevalent Gleason grades  [32]
    • Grade groups: prognostic categories based on the Gleason score that are used to guide management [31]
Gleason grading systemAdenocarcinoma of the prostate (resection specimen)Prostate cancer
Gleason score and grade groups are used to grade the metastatic potential of prostate adenocarcinoma based on gland-forming differentiation.

Evaluation of tumor extent [21][22][33]

  • mpMRI  provides information on local tumor extent (e.g., tumor size and volume).
  • Additional imaging to assess for local tumor extent and metastasis to guide management: [21]
    • Recommended in patients with intermediate or high-risk prostate cancer (i.e., patients with PSA > 10 ng/mL  and an unfavorable grade group
    • Not routinely recommended for patients with low or very low-risk prostate cancer (i.e., patients with PSA < 10 ng/mL, a favorable grade group, and low tumor burden in biopsy cores)
  • Cross-sectional imaging (CT, MRI, or PET-CT scan) is recommended to identify:  [34][35]
  • Assessment of bone metastases
mpMRI is the preferred method for detecting local tumor extent (including recurrent prostate cancer) and PET-CT is preferred to evaluate for metastatic disease. [34][35]
 are the most common nonnodal sites of 

Staging

The TNM staging system is based on American Joint Committee on Cancer recommendations (see “Grading and staging” in “General oncology”). Broadly, prostate cancer is divided into the following clinical stages.  [21][37][38]
  • Localized prostate cancer
  • Locally advanced prostate cancer  [39]
  • Metastatic prostate cancer

Management

Approach [21][33]

Management options for prostate cancer depend on the cancer stage, presence of high-risk features, and the patient's life expectancy. The impact of potential adverse effects of treatment on quality of life should be discussed with the patient prior to treatment initiation.

Watchful waiting [21]

  • Indications: recommended approach if all of the following apply
    • Limited life expectancy (≤ 5 years)
    • Slow-growing tumor (i.e., low-risk or intermediate-risk localized tumors)
    • Asymptomatic or minimal symptoms
  • Method
    • Regular monitoring with scheduled DRE and serum PSA levels (less intensive follow-up than active surveillance). 
    • Initiate definitive management according to cancer stage only when symptoms occur.

Active surveillance [21][40]

Androgen deprivation  [33][41]

Androgen deprivation therapy (ADT)

Androgen synthesis inhibitors and androgen receptor antagonists [42]

Initiate prophylaxis against treatment-induced osteoporosis and fractures in all patients on androgen deprivation and/or glucocorticoids.
First-generation antiandrogens (flutamide and bicalutamide) are used only for the short-term management of a testosterone flare. [43]

Radiation therapy [21][44]

Radical prostatectomy [21]

Radical prostatectomy involves the removal of the vas deferens, resulting in infertility.

Chemotherapy [33]

Management of bone health [48][49][50]

Prostate cancer patients are at an increased risk of skeletal features due to osteoporosis (treatment-induced and age-related) and bone metastases. [33]

Prophylaxis against treatment-induced osteoporosis and fractures

Management of skeletal events [51]

Patients with known vertebral metastatic disease and new neurological symptoms must have an urgent MRI to rule out spinal cord compression.

Follow-up

  • Monitor serum total PSA levels. [52]
    • Every 6 months for the first 5 years, then annually for patients who have had definitive local therapy 
    • Every 3–6 months for patients on ADT
  • Consider assessing PSA velocity (PSA doubling time); a significant rise or short doubling time suggests a recurrence. [11]
  • Arrange further studies for patients with abnormal PSA values.
    • After radical prostatectomy: Any measurable PSA value should prompt evaluation for recurrence.
    • After radiation therapy: Any rise in PSA from nadir should prompt evaluation for recurrence.  [52]
  • Annual DRE: to monitor for prostate cancer recurrence and rectal cancer  [46]

Screening

General principles [53]

Given the indolent nature of prostate cancer and the significant potential for treatment-related decline in quality of life, patients should be educated on the risks and benefits of participating in screening and undergoing treatment if cancer is detected. For patients with a limited life expectancy, neither screening nor treatment may be appropriate.  [21][54]
  • PSA screening is controversial as it has:
    • A high false-positive rate  [53]
    • A high detection rate of clinically insignificant cancers (leading to overdiagnosis)  [53]
    • Minimal or no effect on prostate cancer-related mortality.  [55][56][57]
  • Patient harm may occur as a result of testing and/or treatment initiated by a positive PSA screening test. 
Because of the low benefit and potential risk associated with PSA screening, patients should be involved in the decision to screen for prostate cancer. [6]

Screening recommendations [54][58]

  • Recommendations for screening are based on age and life expectancy and differ between the USPSTF and AUA. [54][58]
    • USPSTF: Offer screening to all individuals between 55 and 69 years.
    • AUA
  • Screening is not recommended for patients with a life expectancy < 10 years. [58]

Screening modalities [6][58]

Prognosis

  • The most important prognostic indicator for prostate cancer is the histological grade (i.e., grade group or Gleason score).  [38]
  • Broadly, patients with cancer confined to the prostate and pretreatment PSA levels < 10 ng/mL have a favorable prognosis.  [21][61]
Grade groups for prostate cancer [31][62]
Grade group5-year survival after radical prostatectomy
1≤ 696%
23 + 4 = 788%
34 + 3 = 763%
44 + 4 = 848%
59 or 1026%

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

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