The Current Status of Prostate Cancer**ACADEMY ORATION delivered by Dr. Mukund S. Joshi, President, NAMS (India) during the NAMSCON 2018 held at the Mahatma Gandhi Medical College & Research Institute, Puducherry.
Authors: Joshi Mukund S. 
Published: May 2020

Prostate cancer (PC) is the commonest malignancy in men that causes significant morbidity and mortality. The incidence has quadrupled in the last three decades. This is predominantly due to its increased detection by excellent newer techniques like Prostate-specific antigen (PSA) evaluation, Transrectal ultrasonography (TRUS), Transrectal ultrasound-guided biopsy, Contrast enhanced ultra sound studies, Multiparametric (Mp) MRI (MpMRI) and Nuclear medicine. Its incidence shows a rise in India. With the availability of PSA and trans-rectal biopsy, nowadays the majority of prostate cancers (PC) are diagnosed at an asymptomatic early stage (T1). Most PC are adenocarcinomas while a small percentage are ductal carcinomas, mucinous carcinomas, signet ring cell carcinomas and small cell carcinomas. These variants have poor prognosis.

The anatomy of prostate will help us to further understand the basis of TRUS studies. The whole prostate can be divided into Transition Zone (TZ),Central Zone (CZ) and Peripheral Zone (PZ). This zonal anatomy of prostate is vital to understand the PC, since PC is predominantly seen as follows: TZ –20%; CZ – 10%; and PZ – 70%.

PSA is an extremely valuable tool in the evaluation of PC. It is exclusively produced by the prostate and to a lesser extent by the seminal vesicles. It is present in all post-pubertal men and absent in women and men following radical prostatectomy. Though the PSA is a vital parameter to detect PC, it can also be elevated in: i) Benign prostrate hypertrophy; ii) Prostate inflammation; iii) Prostatic infarct; iv) Post-digital rectal examination; and v) Sexual activity. The normal value of PSA is 0-4 ng/mL. The two techniques that are available to assess PSA levels are polyclonal assay or monoclonal assay. The monoclonal assay is the most commonly used method the world over. The accepted PSA values are: <4ng/mL (normal); 4.0-10.00ng/mL (borderline) and >10 ng/mL (abnormal). Other than normal PSA values, there are other PSA parameters which are often useful in confirming the diagnosis of PC. These are: i) PSA density; ii) PSA velocity; iii) PSA doubling time; iv) Other markers like PCA3; and v) PC is associated with more protein bound PSA (less free PSA) than in BPH.

Free PSA (FPSA) can enhance the specificity of the total PSA value for detection of the PC while reducing the number of unnecessary biopsies.

Another new finding is that of levels of insulin like growth factor binding protein-2 (IGFBP-2) appear to be directly associated with the presence of PC.

Prostate Biopsy: Ultrasound guided biopsy of the prostate still remains the most important technique for the diagnosis of PC. Different biopsies which are used for diagnosis of PC are: Saturation Biopsy, MRI Guided Biopsy and Fusion Biopsy.

Use of Gleason Score for grading the PC: Gleason score is the grading system used to determine the aggressiveness of PC. This grading system can be used to choose appropriate treatment options. The tumour grades provide important information regarding how fast the cancer is likely to be growing and the likelihood of the cancer spreading to other parts of the body such as lymph nodes or bones. The pathologist assigns the grade of the tumour when he or she looks at the malignant cells under the microscope. The higher the Gleason grade, the more aggressive is the tumour.

Histopathology: Variants of usual acinar adenocarcinoma defined in 2004 by the WHO, include atrophic, pseudohyperplastic, foamy, colloid, signet ring, etc. Recently, variants not included in the 2004 WHO classification are microcysticadeno carcinoma, prostatic intraepithelial neoplasia –adenocarcinoma, large cell neuro endocrine carcinoma and pleomorphic giant cell carcinoma.

Other diagnostic modalities for PC are Colour Flow Imaging, Elastography, Contrast Enhanced Ultrasound (CEUS), MR Imaging of Prostate Malignancies. The MR Imaging consisting of the following:

Prostate Imaging Reporting and Data System (PIRADS) refers to a structured reporting scheme for evaluating the prostate for PC.

T1-weighted images are not helpful in differentiating different zones or detecting the lesion. However, invasion of neurovascular bundle, haemorrhage within the gland and loco-regional lymphadenopathy is better visualized on this sequence.

DWI imaging plays an important role in determining PIRADS score, predominantly in peripheral zone neoplasm. It utilizes proton diffusion properties in water to produce image contrast. Thus prostate malignancy appears bright (hyperintense) on DWI with corresponding low values on ADC map (dark- hypo intense).Of all functional MR imaging techniques, DW imaging is the most practical and simple in its use.

Dynamic Contrast Scan is considered positive if a suspected lesion/ nodule on T2-W or DWI image reveals earlier than normal or more than normal enhancement (hyper enhancement), as routinely seen in lesions with malignant etiology.

MR Spectroscopy reflects resonance frequencies that are unique for protons in different metabolites present at the sampled location. A change in the ratios of concentrations of these metabolites suggests abnormality within the tissue. Normal PZ has high concentration of citrate and polyamines and low concentration of choline and creatinine. A reversal of these, i.e. decrease in citrate peak due to altered metabolism and increase in choline and creatinine peaks in a suspected nodule on T2-W image may suggest malignancy. Recent studies reveal that MR spectroscopy is more specific and less sensitive that anatomic T2-W scan.

Current Modalities of Prostate Cancer Treatments

There are a wide variety of treatments available for the management of prostate cancer. Radical prostatectomy, external beam radiation and radioactive prostate seed implant are potential cures for the prostate cancer. Hormone therapy may force the cancer into a prolonged remission but does not provide a cure unless it is combined with other treatments. The most commonly used treatments include the following:

Watchful Waiting (Active surveillance)

Radical Prostatectomy (Robot assisted radical prostatectomy; Laparoscopic prostatectomy)

Radiation Therapy (External beam radiation; Radioactive prostate seed implants)

Hormone Therapy

Combination of Therapies

High Intensity Focused Ultrasound (HIFU) or Magnetic Resonance-guided Focussed Ultrasound Surgery (MRgFUS)

Others (Cryotherapy; Photodynamic therapy)

Metastatic Disease

Hormonal therapy (orchidectomy)

Anti androgens

Luteinizing Hormone-releasing Hormone (LHRH) Agonists (Leuprolide; Goserelin; Triptorelin; Histrelin) – monthly to annual depot injection S.C. implants

Metastatic PC responds to androgen- ablation/deprivation therapy, which heralded the beginning of a new era PC therapy.