Nonmetastatic Prostate cancer management

Localized prostate cancer is a heterogeneous disease with some cancers growing slowly, staying dormant for decades, while others grow slowly in progress over the years. 

A small number of Prostate cancer patients present as aggressive, rapidly progressive and fail to respond to local treatments.

Nearly 3/4 of patients present with localized disease (74%) confined to the primary site.

13% of patients present with regional disease, which is spread to regional lymph nodes at diagnosis. 

Approximately 7% of patients present with disease that has metastasized at diagnosis.

Risk stratification helps to determine the likelihood of the prostate cancer remain confined versus spreading and disease progression or metastases after treatment.

Tools for risk stratification: digital rectal examination, Gleason score (6–10) or a Grade Group (1-5), with a percentage of total positive cores and percentage of cancer per core, PSA level, PSA density, and life expectancy, mri imaging, ultrasound, gene expression biomarkers, and germline testing. 

Patient’s tumors can be divided into low risk, including very low risk, intermediate risk, including favorable and unfavorable, high risk and very high risk groups.

Multiparametric prostate MRI and  PSMA PET/CT scans improve risk stratification for newly diagnosed prostate cancer patients. 

Multiparametric prostate MRI is an established procedure to determine the need for biopsy and to improve the detection of clinically significant prostate cancer, providing an accurate measurement to determine prostate size and to calculate PSA density.

The prostate imaging reporting in data system (PI- RADS) rating from one to five with the latter helping to determine the location and extent of significant cancer.

PSMA PET/CT allows higher sensitivity and specificity beyond what a bone scan of pelvic CT scan can yield in terms of risk stratification.

Germline multi gene testing includes: BRCA1, BRCA2, ATM, PALB 2, CHEK2, MLH1, MSH2, MSH6 and PMS2.

Active surveillance involves monitoring patients diagnosed with low risk or favorable intermediate risk prostate cancer, with the expectation to intervene with curative intent upon disease progression.

Life expectancy is a key determinant for the treatment options of observation, active surveillance, and definitive treatment. 

Active surveillance is preferred for patients with very low risk prostate prostate cancer and a life expectancy of 10 years or greater whereas observation is preferred for those with the life expectancy of less than 10 years and a very low risk disease. 

Patients with favorable intermediate risk prostate cancer and a life expectancy of greater than 10 years may also consider active surveillance.

Observation involves monitoring a patient with physical examination annually, without further testing and intervening if the patient becomes symptomatic.

Active surveillance involves PSA testing no more than every six months, digital rectal exam no more than every 12 months, and repeat prostate biopsy no more than every 12 months.

Moderate hypofractionation radiation is the preferred modality involving giving moderate amounts of doses for 4 to 5 weeks.

Conventional fractionation involves 37 to 45 treatments with lower doses. 

Ultra hypofractionation delivers radiation in 5-7 treatment during a period of one to two weeks.

Brachytherapy or implant therapy, involves two types of implants, a permanent implant of low-dose radiation, using iodine, palladium, or cesium, and a temporary implant of high-dose radiation using Indium192. 

A combination of external radiation with either a permanent implant, or low-dose, radiation or temporary implant with temporary high dose radiation is another option.

Radical prostatectomy is appropriate for patients with a life expectancy of 10 years or greater with clinically localized prostate cancer that can be completely excised surgically.

A pelvic lymph node dissection should be performed at prostatectomy with those with the unfavorable, intermediate risk, high risk, or very high risk disease.

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