Prostate%20cancer Management

Observation/Watchful Waiting

• Based on the premise that it may be more beneficial to provide palliative therapy at the time when local or metastatic progression occurs, thereby maintaining quality of life
  • Also prompts a change in diagnostic tests when symptoms suggest disease progression
• Management option for:
  • Patients who prefer not to undergo treatments
  • Elderly men or immunocompromised patients with comorbidities and/or poor prognostic features
  • Patients who will not benefit but will only incur harm from definitive treatments

• Recommended for asymptomatic patients in very-low-, low-, and intermediate-risk groups with life expectancy of ≤5 years, and asymptomatic patients with very-low- and low-risk prostate cancer with life expectancy 5–10 years
• May be considered in asymptomatic patients with favorable and unfavorable intermediate-risk prostate cancer with life expectancy between 5–10 years, and asymptomatic patients with high risk, very-high risk, regional, and metastatic prostate cancer with life expectancy of ≤5 years
• Recommended for patients with non-metastatic castration-resistant prostate cancer (CRPC), with continued androgen deprivation therapy
• Includes monitoring of prostate-specific antigen (PSA) and digital rectal examination (DRE) every 6 months

Advantage

• Potential harm from different unnecessary therapies and early initiation and/or continuous androgen deprivation therapy may be avoided

Disadvantage

• Increases the risk for urinary retention and pathologic fracture without prior symptoms or increasing PSA

Active Surveillance

• Watchful waiting while actively monitoring the disease course to be able to intervene when the disease progresses, delaying the potential side effects of treatments
• Preferred for patients with very low-risk prostate cancer with life expectancy of 10-20 years  
• Preferred for patients with low-risk prostate cancer with life expectancy of >20 years
• Considered for patients with favorable intermediate-risk prostate cancer with life expectancy of >10 years
• Criteria for the use of active surveillance include: Clinical stage T1c or T2a, grade group 1-2, ≤3 positive cores with ≤50% cancer involvement in any core, PSA <10 ng/mL, PSA density <0.15 ng/mL/g
  • Decision to use active surveillance should not be based solely on above criteria 
• Treatment option for those with low-risk localized disease and candidates for radical prostatectomy or radiotherapy
  • May also be suggested to asymptomatic patients, elderly men, and those with comorbidities
• Presence of any of the following pathology should prompt exclusion for active surveillance: Predominant ductal carcinoma, sarcomatoid carcinoma, small cell carcinoma, extraprostatic extension (EPE) or lymphovascular invasion (LVI) in needle biopsy, perineal invasion

Inclusions

• Initial: Multiparametric MRI (mpMRI) and/or prostate biopsy if not performed previously
• 1st year: Monitoring of PSA every 6 months and DRE, prostate biopsy and mpMRI at 12 months
  • Repeat needle biopsy within 6-12 months from initial diagnosis is indicated for patients with <10 cores; once every 3 years for low-risk patients for 10 years
  • Repeat biopsy may not be performed if the life expectancy is <10 years

• 2nd-4th year: PSA monitoring every 3-6 months and DRE every 6-12 months
• 5th year and yearly thereafter: PSA every 6 months and DRE every 12 months
• PSA kinetics (doubling time and velocity) should be monitored all throughout active surveillance duration

Advantages

• Eligible patients may avoid or delay treatment 
• Potential harm from different treatment modalities may be avoided
• Patient may go back to their normal activities and may retain present quality of life
• Smaller/undiagnosed malignancies will remain therapy-naive, thereby preventing future treatment resistance
• Expenses may be reserved for more definitive treatments

Disadvantages

• Chance for early treatment and cure may be missed
• High propensity for disease progression and metastasis
• Tumor size may increase, making surgery and medical management more difficult
• Preservation of function may be more difficult for more aggressive and bigger tumors
• Increased anxiety due to untreated malignancy and uncertainty of disease progression
• Intermittent monitoring with diagnostics and clinic visits are required

Local Recurrence

• Initial PSA levels of ≥0.2 ng/mL and subsequent confirmatory levels of ≥0.2 ng/mL signifies biochemical recurrence
  • Biochemical recurrence can be categorized as either:
    • PSA level that fails to fall to undetectable levels post-radical prostatectomy
    • PSA level undetectable post-radical prostatectomy but with ≥2 subsequent laboratory results with detectable PSA level
    • Persistent or low PSA levels due to slow PSA metabolism or residual benign tissue
• Endorectal ultrasound may be considered to rule out recurrence after radical prostatectomy

Follow-up Examinations

Prostate-Specific Antigen (PSA) Monitoring

• PSA levels should be significantly lower after radical prostatectomy, radiation therapy, cryotherapy and other treatments
• Should be done every 3-6 months x 5 years, then every 6-12 months x 5 years, then annually
• Asymptomatic patients do not require further imaging if PSA is stable

Digital Rectal Exam (DRE)

• Timing of DRE after EBRT or radical prostatectomy: Annual

Bone Scan

• May be done if with symptoms or PSA levels rise after local therapy
• Should be performed every 6-12 months to monitor ADT and 8-12 week-interval for patients with castration-resistant prostate cancer (CRPC)
• Bone densitometry measurement by dual-energy X-ray absorptiometry (DEXA) scans should be obtained regularly especially in patients at high risk for skeletal side effects and for monitoring of treatment response to Denosumab or bisphosphonates

Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) Scan

• May be considered if the following occurs after radical prostatectomy:
  • PSA levels still detectable (PSA persistence)
  • Previously undetectable PSA is suddenly detected (PSA recurrence)
  • Recorded PSA increases in >2 PSA level examinations
  • Increasing PSA or positive DRE after radical prostatectomy

• Spinal MRI to detect cord compression is recommended in CRPC patients with vertebral metastases and neurological symptoms
• For patients without any evidence of metastases, the following imaging studies may be considered:
  • For further soft tissue and bone evaluation: C-11 choline PET/CT, PET/MRI, F-18 fluciclovine PET/CT or PET/MRI
  • For further bone evaluation: F-18 sodium fluoride PET/CT or PET/MRI

PET/CT Scan and PET/MRI

• Has comparable sensitivity and specificity with other FDA-approved imaging agents in detecting recurrences at lower PSA levels 
  • PSA level cut-off of Choline PET/CT is between 1-2 ng/mL and PSMA PET/CT is <1 ng/mL
• Has good sensitivity in prostate cancer restaging
• Useful in identifying CRPC and in predicting response to therapy

Salvage Treatments

• Local salvage therapy options include salvage radical prostatectomy, HIFU, cryoablation and brachytherapy
  • Considered in patients with low comorbidity, life expectancy of at least 10 years, a presalvage therapy PSA level <10 ng/mL, initial ISUP ≤3 initial clinical stage of T1/T2 and no lymph node involvement
• Salvage radiotherapy is a treatment option for patients with increasing PSA levels after radical prostatectomy and no presence of distant metastasis; should be given once biochemical recurrence has been confirmed
  • May consider hormone therapy if PSA is 0.20 ng/mL postoperatively
  • Recommended doses for adjuvant/salvage post-prostatectomy RT are 64-72 Gy
• Salvage brachytherapy (permanent low dose-rate or temporary high dose-rate) may be considered in patients with confirmed local recurrence after EBRT or brachytherapy
• Primary salvage or adjuvant radiotherapy may be considered in patients with PSA recurrence post-radical prostatectomy if without distant metastases 
  • Patients with pathological T3 prostate cancer, positive margin/s or seminal vesicle involvement may be given adjuvant radiotherapy, usually given within 1 year post-radical prostatectomy and after recovery from operative side effects
  • Patients with previously undetectable PSA that became detectable on 2 measurements or with persistently detectable PSA post-radical prostatectomy may be given salvage radiotherapy
• Early salvage IMRT/VMAT with IGRT may be used for patients with 2 consecutive biochemical relapse after radical prostatectomy
• Salvage radical prostatectomy, HIFU, or cryosurgical ablation may be used for patients with local recurrence after radiotherapy or cryotherapy
• Salvage ADT alone may be considered in patients with proven or high suspicion of metastasis, symptomatic local disease, or biochemical relapse with rapid PSA doubling time
• Salvage cryoablation of the prostate may be an alternative to salvage radical prostatectomy
• Salvage high-intensity focused ultrasound (HIFU) may be used as an alternative option for radiation-recurrent prostate cancer