Prostate Carcinoma: Urologist ’ s Perspective

inferred from a study on Ca P screening. 6 But 17 years of follow-up with the prostate, lung, colorectal, ovarian screening trial showed no difference in mortality. 7 Most of the PSA testing is done nowadays in men with lower urinary tract symptoms (LUTSs) who visit a general physician or a urologist. PSA is the ﬁ rst widely used marker evaluated to diagnose Ca P. It is a member of human kallikrein (hK2) gene family. It is a serine protease helpful in lysis of semen coagulum. Although PSA is elevated in most cases of Ca P, it is not cancer speci ﬁ c. It is fairly organ speci ﬁ c, but not cancer speci ﬁ c. 8

The serum concentration of PSA gradually increases with age.Age-specific PSA level is important in selecting patients for biopsy or further evaluation. 9The "normal" PSA value cannot be defined.Thompson et al performed prostate biopsies of all patients with PSA less than 4 ng/mL.Fifteen percent of them were found to have Ca P. Interestingly, only 16% of them had clinically significant Ca P with Gleason score of 7. 10 22 to 25% of those with PSA of 4 to 10 ng/mL and 50 to 67% of those with PSA greater than 10 ng/mL have prostate Ca P. 11 To improve specificity, analysis of molecular derivatives like free and complexed PSA are used.It is mainly used in PSA values between 2 and 10 ng/dL.The cutoff value for free PSA proportion varies between 15 and 25% in various studies, with more specificity if free PSA is low.Twenty-five percent cutoff led to 20% reduction in biopsies and 95% ca P detection. 12,13he other derivatives of PSA are PSA density and PSA velocity.In PSA values between 4 and 10 ng/mL, PSA density of more than 0.15 had high yield in biopsies.PSA density is calculated by dividing the PSA value by the prostate volume.It is a parameter in risk stratification of patients to manage with active surveillance.It is a marker of aggressiveness of the tumor.PSA velocity is the rate of PSA rise over a particular time period.PSA velocity of more than 0.75 ng/mL/y is significantly associated with Ca p. 14,15 Prostate Health Index (PHI) combines total PSA (tPSA), free PSA (fPSA), and p2PSA (prepro -PSA) levels with a specific formula to get the probability of Ca P and the need for biopsy. 16The 4-kallikrein (4K) panel test is another recent addition to predict the probability of positive clinically significant cancer.It combines the values of tPSA, fPSA, single-chain iPSA (intact), and hK2 to formulate the probability of Ca P and the need for biopsy. 17PCA3 and TMPRSS: ERG gene fusion mRNA are the urinary biomarkers in line needing further studies for use in the diagnosis of Ca P. 18

Radiological Investigations in Prostate Cancer
Ultrasonography (USG) and magnetic resonance imaging (MRI) are the cornerstones in the diagnosis and management of Ca P.

Ultrasonography in the Diagnosis of Ca P
Transabdominal USG has a limited role in the diagnosis of ca P. It is mainly useful in assessing the detrusor wall thickness.Transrectal ultrasound is useful in accurate measurement of prostate volume.It is also the standard for guided biopsy of the prostate.

Transrectal Ultrasound Guided Biopsy
Twelve-core biopsy is the standard for diagnosis of Ca P. Each biopsy core needs to be sent separately as a template.This detail will help in planning nerve sparing during radical prostatectomy.Higher number of cores may increase the yield, especially in large glands.transrectal ultrasound (TRUS) guided biopsy can be performed by both transrectal and transperineal approaches.The transrectal approach is the standard for prostate biopsies.But transperineal biopsies are preferred now, with the advantage of less infections and higher yield from anterior gland biopsies and apical biopsies. 19Targeted biopsies from hypoechoic and other suspicious areas can be done in addition to standard cores.

Magnetic Resonance Imaging in Prostate Cancer
MRI is the cornerstone in the diagnosis and management of Ca P in the present era.Multiparametric MRI (mpMRI) with PI-RADS 2.1 reporting is the standard now. 20MRI-guided fusion biopsies increase the yield of the biopsy cores.Standard 12core biopsies are mandatory along with targeted biopsies (PIRADS 3, 4, 5 lesions).Clinically significant cancers are picked up more with targeted biopsy cores of PIRADS 4 and 5 lesions (►Fig. 1). 21PIRADS grades of each lesion in the prostate are necessary.The Patient-Reported Outcomes Measurement Information System trial showed that 27% of patients might avoid biopsy by doing a preprocedure mpMRI. 22Thus, mpMRI may be beneficial to avoid unnecessary biopsies and its related complication and diagnose only clinically significant cancers.
The pictorial representation of the target lesions is helpful during radical prostatectomy.These are even more important in the minimally invasive treatment modalities like cryotherapy and high-intensity focused ultrasound to specifically target the lesions.The findings in MRI, which suggest extravesical spread, indicate the need for extra-fascial dissection during radical prostatectomy.
The signal characteristics of the seminal vesicle indicate the presence of inflammation and hemorrhage.It helps while dissecting seminal vesicles to anticipate adhesions around them and precise surgery.Obvious involvement of the seminal vesicles upstages the disease and might change the management options.Prior information regarding the exact prostate volume and the prominent intravesical protrusion of the prostate is necessary to anticipate intraoperative difficulties.The distance of the ureteric orifices from the bladder neck (especially in those with short trigones) will help in preventing injuries to ureteric orifices during bladder neck division.Bladder wall thickness and upper tract status should be known.The presence of significant lymphadenopathy (pelvic) necessitates further evaluation with prostatespecific membrane antigen (PSMA) positron emission tomography (PET) to rule out other sites of metastases.Definite evidence of axial skeleton involvement with sclerotic bone metastases made out on MRI upstages the disease to stage IV.

Positron Emission Tomography
PSMA PET has been used primarily to assess the metastatic status of Ca P. PET may be used to diagnose lymphatic involvement, if nomograms indicate higher probability of metastases.MRI might show enlargement of lymphnodes, but activity in PET is more suggestive of metastases.PSMA PET is also more sensitive for bone metastases compared to Tc-99m methylene diphosphonate bone scan.(68% vs 98%). 23xact load of metastatic disease is essential to decide the management and PSMA PET is helpful in that aspect.Recently PSMA PET has also been evaluated for diagnosis and selection of patients for biopsy, showing promising results. 24

Bone Scan and Computed Tomography
Computed tomography (CT) has limited role in Ca P. Bone scan (Tc MDP), though of lesser sensitivity, is the standard for metastatic workup according to major guidelines.Metastatic lesions light up in bone scan due to osteoblastic activity.SPECT CT with bone scan increases the sensitivity. 23

Pentafecta in Postsurgery Outcomes
Continence, potency, recurrence-free survival, negative surgical margins, and no postoperative complications designate the pentafecta outcome evaluation criteria. 24,25These primarily depend on meticulous preoperative planning and individualization of surgical approach.Target lesions identified in the MRI in the apex or base requires meticulous dissection in the concerned areas to prevent positive margins.

Conclusion
Imaging studies in Ca P are an essential part of treatment planning.Accurate information regarding the tumor location and extent along with that of nearby organs will have an impact on the successful management of Ca P.