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.

PSA Screening

Per NCCN 2023 Guidelines, we discuss PSA screening in average risk men above age of 45.

Per NCCN 2023 Guidelines, we discuss PSA screening in high risk men above age of 40.

Per NCCN 2023 Guidelines, in men 40-75 y/o with PSA> 3, we recommend further evaluation and possibly prostate biopsy based on these evaluations.

Per NCCN 2023 Guidelines, in healthy men >75 y/o with PSA> 4, we recommend further evaluation and possibly prostate biopsy based on these evaluations.

Further evaluation includes multiparametric MRI and biomarkers that improve the specificity of screening.

PSA Velocity

Per 2023 NCCN Guidelines, PSAV (PSAV ≥0.35 ng/mL/y) is only one criterion to consider when deciding whether to perform biopsy for individuals with low PSA levels.

IsoPSA

Might be considered in men > 50 with PSA> 4. Cut-off associated with risk threshold is >6.

Other Biomarkers

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

Free PSA: If< 10% 

Prostate Health Index (PHI) :

If >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: If>15.6- EPI test is a non-invasive urine test.

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

Multi-parametric MRI

We  recommend mpMRI for patient who have elevated PSA and also  before repeat biopsy when clinical suspicion of prostate cancer  persists in spite of negative biopsies.

Multiparametric MRI 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)

Prostate Biopsy Risks

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Prostate Biopsy Antibiotics

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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

Other Pathology Reports

Intraductal Carcinoma without Invasive Cancer: Per NCCN 2023 Guidelines, proceeding directly to definitive therapy should be considered when IDC is seen on biopsy in the absence of invasive carcinoma

Atypical Intraductal Proliferation without Invasive Cancer (AIP): Per NCCN 2023 Guidelines, when AIP is seen on biopsy in the absence of invasive carcinoma, repeat biopsy using MRI targeting and systematic biopsy to look for invasive carcinoma is recommended.

High-Grade Prostatic Intraepithelial Neoplasia (HGPIN): Per NCCN 2023 Guidelines, patients with HGPIN should be followed with PSA and DRE at 6- to 24month intervals and should consider biomarker testing and/or multiparametric MRI.  Repeat biopsy with refined biopsy techniques should be performed based on risk.

Atypia, Suspicious for Cancer: Proceed similar to HGPIN

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.

Molecular biomarkers

Oncotype Dx Prostate, Prolaris, Decipher, and ProMark

Oncotype DX Prostate

Gene expression profiles (GEPs) evaluate the expression of several genes using biopsy tissue. It helps with risk stratification in prostate cancer treatment decision making.

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

Watchful waiting

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.

Active surveillance

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

To review outcomes click here. 

Radical prostatectomy/ Radiation Therapy

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

Moderate hypofractionation 

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

Ultrahypofractionation

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.

Androgen deprivation therapy

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.

Xi Robotic Radical Prostatectomy Sutures

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Robotic Radical Prostatectomy Outcomes 

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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  ≥ 0.4 , 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.

Non-Metastatic Castration-Resistant Prostate Cancer

If PSA doubling time is <10 months, we continue  the androgen deprivation therapy. 

We add Apalutamide or Enzalutamide in this setting.

Metastatic Hormone Sensitive Prostate Cancer

We recommend androgen deprivation therapy 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 this setting.

Androgen deprivation therapy alone is no longer considered sufficient in the 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. 

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 the 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 the 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 deficiency or microsatellite instability high condition. 

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 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).

Tools

Staging Form

TNM staging: click here. 

AJCC staging: click here. 

Prostate Tumor Volume & Density

Click here. 

PSA Doubling Time (PSADT)

Click here.