Prostate Cancer

Page updated Winter 2021.
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Basics and Diagnosis

Epidemiology

Prostate cancer is the most common visceral malignancy in men in US.

Prostate cancer is the third leading cause of cancer-related deaths in US.

Genetics

HOXB13 and BRCA are two genes that are associated with increased risk of prostate cancer.

BRCA-related tumors are more aggressive.

Diet

No specific preventive or dietary measures are recommended to reduce the risk of developing prostate cancer.

Prostate Cancer Screening

We recommend PSA screening to men who are 55-69 years old.

We will proceed based on the patient preferences.

We also discuss PSA screening with men 40-55 years who are at higher risk. This includes African American men and men with strong family history of prostate, breast, and ovarian cancer.

Some men above 70 years who are in excellent health might benefit from PSA screening.

We generally recommend PSA test every 2 years.

Biopsy

We, per NCCN guidelines, consider prostate biopsy if PSA> 3.

We might consider other biomarkers, discussed below,  for patient with PSA 2-10.

The following  biomarkers and values are in favor of prostate cancer and/or high grade disease:

Free PSA < 10% 

Prostate Health Index (PHI) >35. It is measured from values of 3 PSA subtypes in the blood. 

4 K Score: It provides a percentage risk (ranging from 1-95%) of having aggressive prostate cancer on the biopsy. It is measured from values of four prostate-specific kallikreins in the blood. Of note, PSA is a kallikrein.

EPI score>15.6- EPI test is a non-invasive urine test.

PCA3 > 35. It is specially helpful after a negative  biopsy. It is a urine test  which is done after digital rectal examination. 

Responds to Local Therapy

Patient with localized cancer with PSA<10 who do not have PSA Velocity of >2 / year most likely will respond to local therapy.

Biopsy

We recommend  transrectal ultrasound (TRUS)-guided biopsy protocols involving 12 cores. 

We recommend a  fluoroquinolone for less than 24 hours.

Grade Group categorizations 

Grade Group 1- Gleason score ≤6
Grade Group 2- Gleason score 3+4=7
Grade Group 3- Gleason score 4+3=7
Grade Group 4- Gleason score 4+4=8
Grade Group 5- Gleason scores 9 and 10

Multi-parametric MRI

We recommend multiparametric magnetic resonance imaging (mpMRI) before repeat biopsy when clinical suspicion of prostate cancer  persists in spite of negative biopsies.

Multiparametric magnetic resonance role in biochemical failure has been discussed under corresponding section.

PI-RADS=1 (Very Low risk of prostate cancer)

PI-RADS=2 (Low risk of prostate cancer)

PI-RADS=3 (Intermediate risk of prostate cancer)

PI-RADS=5 (High risk of prostate cancer)

PI-RADS=5 (Very High risk of prostate cancer)

Staging 

Bone Scan: We perform bone scan if patient is symptomatic or if PSA >20.

CT or MRI of Abdomen and Pelvis: We perform CT or MRI of abdomen and pelvis if PSA>20, or Gleason Score   8 or if patent has locally advanced disease.

Lymphadenectomy: We may avoid lymphadenectomy if PSA <10 and Gleason Score  6.



Localized Prostate Cancer

Risk Stratification

Very Low Risk 
PSA <10  & Grade Group 1 & clinical stage T1-T2a  & <34% of biopsy cores positive & no core with >50% involved & PSA density <0.15 
Low Risk
PSA <10  & Grade Group 1 & clinical stage T1-T2a
Intermediate Risk Favorable
Grade Group 1 (with PSA 10-<20) OR Grade Group 2 (with PSA<10)
Intermediate Risk Unfavorable:
Grade Group 2 (with either PSA 10-<20 or clinical stage T2b-c) OR Grade Group 3 (with PSA < 20)
High Risk
PSA >20 ng/ml OR Grade Group 4-5 OR clinical stage >T3

Localized Prostate Cancer Management

We recommend observation or watchful waiting for low and intermediate risk patients who have life expectancy of ≤ 5 years.

We may consider observation or watchful waiting for asymptomatic high risk patients who have life expectancy of ≤ 5 years. We may consider androgen deprivation therapy or radiation therapy for selected patients in this group.

We recommend active surveillance for very low risk patients and most of low risk patients. 

We recommend radical prostatectomy or radiation therapy plus androgen deprivation therapy for intermediate and high risk patients.

We recommend moderate hypofractionation for patients who choose radiation therapyIGRT is recommended. Regimens include 6000 cGy delivered in 20 fractions of 300 cGy and 7000 cGy delivered in 28 fractions of 250 cGy.

Ultrahypofractionation may be suggested to low and intermediate, but not to high risk patients. IGRT is recommended. This protocol consists of 3500 to 3625 cGy in 5 fractions of 700 to 725 cGy. Prostate should be smaller than 100 cm3.

We recommend 24-36 months of androgen deprivation therapy for high risk patients who choose radiation therapy.

Locally Advanced Prostate Cancer Management

Radical prostatectomy, if technically doable,  can result in disease-free survival in more than half of men at 8 to 10 years. 

We recommend adjuvant radiotherapy to the patients who have seminal vesicle invasion, positive surgical margins, and extraprostatic extension.

Radiation therapy plus androgen deprivation therapy is the other option in this setting.

Biochemical Recurrence after Radical Prostatectomy

PSA > 0.2 with a second confirmatory level > 0.2.

Salvage Radiotherapy

Multiparametric MRI can detect local recurrences in the prostatic bed, but its sensitivity in patients with PSA level < 0.5 ng/mL remains controversial.

We generally do not take biopsy. Decision is made based on biochemical recurrence. 

We recommend salvage radiotherapy to patients with PSA or local recurrence after radical prostatectomy, preferably when the PSA level is < 0.5.

If PSA  ≥ 1, we recommend a prostate-specific membrane antigen positron emission tomography computed tomography (PSMA PET/CT), if available, or a choline PET/CT imaging.

We recommend hormone therapy to patients treated with salvage radiotherapy 

Biochemical Failure after Radiation Therapy

PSA ≥ 2.0 above the nadir. This definition is used for  external beam radiotherapy and interstitial prostate brachytherapy, even if these treatments were accompanied by androgen deprivation therapy.

We recommend prostate biopsy before treating the patient.

Biopsy should be obtained 18-24 months after treatment. 

Transrectal US is not reliable in depicting local recurrences after radiation therapy.

Multiparametric MRI has been associated with excellent results and can be used for biopsy targeting and guiding local salvage treatment. 

We recommend PSMA PET/CT (if available) or choline PET/CT imaging to rule out positive lymph nodes or distant metastases before curative salvage treatment. 


Advanced Prostate Cancer
Positive Lymph Nodes at Prostatectomy
Androgen deprivation therapy can be considered.

PSA Recurrence with No Metastases after Exhaustion of Local Therapy
We recommend CT or MRI or PET CT scan and Bone Scan for patients who have PSA recurrence after exhaustion of local therapy if PSA doubling time is <12 months.

If imaging is negative in this group of patients, we usually just observe them. We do not start androgen deprivation therapy at this point.

Metastatic Hormone Sensitive Prostate Cancer:
We recommend androgen deprivation therapy with LHRH agonists or antagonists or surgical castration in this setting.

Androgen deprivation therapy options are LHRH agonists (
Leuprolide, Goserelin, Triptorelin) or antagonists (Degarelix, Abarelix, Cetrorelix) or surgical castration.

Except to block testosterone flare when we start LHRH agonists, we do not add bicalutamide, flutamide, nilutamide to LHRH agonists. They are used for 4 weeks in that setting
Androgen deprivation therapy alone is no longer considered sufficient in management of this group of patients.

We add abiraterone acetate plus prednisone, apalutamide, enzalutamide or docetaxel in this setting.

If the patient has low volume metastatic disease, we may also add primary radiotherapy to the prostate. 

Non-Metastatic Castration-Resistant Prostate Cancer

If PSA doubling time is <10 months, we continue  androgen deprivation therapy. We add apalutamide or enzalutamide in this setting.

Asymptomatic-minimally symptomatic  Metastatic Castration-Resistant Prostate Cancer

We continue androgen deprivation therapy.

We recommend abiraterone plus prednisone, enzalutamide, docetaxel, or sipuleucel-T these patients.

Symptomatic Metastatic Castration-Resistant Prostate Cancer

We continue androgen deprivation therapy.

We add abiraterone acetate plus prednisone,
enzalutamide or docetaxel.

Radium-223 will be suggested to patients with symptoms from bony metastases, if they don't have visceral metastases or  lymphadenopathy >3cm and if they have not received docetaxel.

In patients who received prior docetaxel, we will recommend cabazitaxel as second line chemotherapy agent, especially if the patient had already received abiraterone acetate plus prednisone or enzalutamide.

Pembrolizumab is an option for patients with mismatch repair deficient or microsatellite instability high. 

Bone Health

Patients need to stop smoking and perform weight bearing exercises.

We recommend denosumab or zoledronic acid to patients at high fracture risk and to Castration-Resistant Prostate Cancer patients with bone metastases.

Survival
Survival after Local Therapy Failure

Patients with a long PSA doubling time (>15 months) have a low likelihood of prostate cancer-specific mortality over a 10 year period and active surveillance may be considered for those with a life expectancy of <10 years. 

In contrast, patients with a PSA doubling time <3 months have a median overall survival of 6 years following PSA failure, and are likely have distant disease.

Survival after Initiation of Androgen Deprivation Therapy

Failure to achieve a PSA nadir of <4.0 ng/mL 7 months after initiation of therapy for metastatic prostate cancer is associated with a very poor prognosis (median survival of approximately 1 year).

Patients with a PSA nadir of <0.2 ng/mL have a relatively good prognosis (median survival of over 6 years).