RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,KARNATAKA,BANGALORE

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DESSSERTATION

1. Name of the candidate and address:DR MAYUR R SHETTY

103 D RANKA CORNER APTS,

14, CAMBRIDGE ROAD

ULSOOR , BANGALORE 560008

2. Name of the institution: KEMPEGOWDA INSTITUTE OF

MEDICAL SCIENCES AND RESEARCH CENTRE.

3. Course of study and subject: M.S. (GENERAL SURGERY)

4. Date of admission to course: June 1st 2010

5. Title of the topic: THE UTILITY OF PROSTATE SPECIFIC

ANTIGEN DENSITY IN DETECTING

CARCINOMA PROSTATE IN MEN WITH PSA

LEVELS OF 4- 10 ng/ml

6. BRIEF RESUME OF THE INTENDED WORK:

6.1 Need for the study:

a) Carcinoma prostate is one of the principle medical problems faced by the male population hence making early and accurate diagnosis crucial.

b) PSA though organ specific is not cancer specificand hence results in difficulties in discriminating malignant and benign prostatic condition in men with only slight raise of PSA levels

c) Diagnosis of prostaticdiseases hence requires a more specific and reliable investigation especially in men with PSA levels of 4-10 ng/ml

d) The results maybe helpful in establishing early prostate cancer detection in Indian men

6.2 Review of literature:

  • The discovery and utilization of tumor markers have positively affected early detection, diagnosis, and staging for many malignancies. By improving early detection, tumor markers contribute to improved curative success rates.
  • Optimal treatment and cure depend not only on accurate and early diagnosis but also on reliable follow-up for efficient detection of clinical recurrence. The identification of new markers and the development of sensitive tools to measure them will contribute to improved cure rates.
  • Among urologic malignancies, prostate cancer has greatly benefited from the discovery and application of tumor markers.
  • Since its discovery in 1979 to clinical application in the late 1980s through 1990s, prostate-specific antigen (PSA) has evolved into an invaluable tool for the detection, staging, and monitoring of men diagnosed with prostate cancer ( Sensabaugh et al, 1978 ; Wang et al, 1979, 1981 [243] [242]; Papsidero et al, 1980 ; Kuriyama et al, 1981 ).
  • The widespread use of PSA screening has generated greater awareness about prostate cancer. During the PSA era, identification of cancers while confined to the prostate has improved curability with either radical prostatectomy or radiation therapy. Whereas the majority of prostate cancers in the 1980s and early 1990s commonly arose with an abnormal digital rectal examination (DRE) or elevated PSA, or both, today most prostate cancer arises as clinically nonpalpable (stage T1c) disease with PSA between 2.5 and 10 ng/mL.
  • All men, regardless of the results of the DRE, should have an ultrasound-guided biopsy if their PSAD is greater than 0.15. Patients with a negative DRE result should undergo a biopsy if the PSAD is greater than 0.10, because 11 of 89 patients with mid-grade lesions would have been missed if a PSAD cutoff of 0.15 was used. Men with a PSA greater than 4 ng/ml should have a rectal ultrasound examination performed to obtain the PSAD.
  • For men with PSA levels between 4 and 10 ng/mL, and more recently 2.5 to 10 ng/mL, the specificity of cancer detection has been more challenging.
  • Cancers discovered within this range are often earlier in stage, and potentially more curable, yet might also represent “insignificant,” potentially non–life-threatening tumors. However, given the considerable overlap in serum PSA concentrations in men with and without prostate cancer, this range has been described as the diagnostic “gray zone.”
  • Benson and colleagues (1992a, 1992b) [10] [11] introduced a method to correlate more directly the degree to which cancer contributes to the serum PSA and to compensate for BPH and prostate size as determined from transrectal ultrasonography.1
  • A direct relationship between PSA density (PSAD) and the likelihood of cancer has been documented ( Seaman et al, 1993 ; Bazinet et al, 1994 ; Rommel et al, 1994 ). For men with a PSA between 4.0 and 10.0 ng/mL and a normal digital rectal examination, a PSAD greater than 0.15 has been suggested as discriminatory for the presence of cancer ( Seaman et al, 1993 ; Bazinet et al, 1994 ).
  • In Asia, a study carried out by Yamamoto et al. (2005) inJapan analyzed 300 patients with a prostate speciWc antigenlevel of 2.5–20 ng/mL and found that the cancer-detectionrate in patients with a PSA density (PSAD) of less than0.10 ng/mL per cc was only 5.6%. They suggested that ifthe indication for biopsy was decided based on the PSAD,then the cancer detection rate might be further improved,with fewer unnecessary biopsies.2
  • By analyzing 147 Japaneseprostate cancer and 253 BPH patients with PSA valuesof 4.1–10 ng/mL, Sakai et al. (2004) suggested that thespeciWcities of tPSA and PSAD were also superior to thatof the f/t PSA ratio, that measurement of the f/t PSA ratiodoes not provide any signiWcant additional information forthe diagnosis and staging of prostate cancer in Japanesemen when tPSA and PSAD values are available.3
  • Cao et al. (2006) analyzed 38prostate cancer and 104 BPH patients with PSA values of4.1–10 ng/mL. They showed that the sensitivity andspecificity of PSA density at a cutoV of 0.13 ng/mL2 was 92.1 and 47.1%, respectively. They suggested that prostatespecific antigen density was a good predictor of prostatecancer.4
  • PSA density hasbeen shown to correlate with prostate cancer presence,aggressiveness, pathologic tumor stage and progressionfreesurvival after treatment (Allan et al. 2003).5
  • A few studies have tried to improve uponthe performance of PSA density by using complexed or free PSA in the numerator or correcting the denominator fortransition zone volume (Sözen et al. 2005; Veneziano et al.2005; Aksoy et al. 2003).6
  • PSA TRANSITIONAL ZONE is more useful than PSAD in detecting prostatecancer in men with intermediate PSA levels of 4.1 to 10.0 ng/mL.At a cutoff value of 0.35 ng • mL–1 • mL–1,the sensitivity and specificity of PSATZ are better than thoseof PSAD. Prostate-specific antigen adjusted for transition zonevolume may also help minimize unnecessary biopsies in patientswith benign disease.7

6.3 Objectives of the study:

My objective is to study 30 cases and to determine

  • Utility of PSA Density as a screening test
  • Comparison between PSA, PSADensity and FREE/ TOTAL PSA ratio
  • Correlation of PSADensity values with HPE findings on TRUS biopsy
  1. Material and methods:

7.1 Source of Data: patients attending urology and surgery OPD with symptoms suggestive of LUTS or with USG/ TRUS findings suggestive of prostate enlargement

7.2 Method of collection of data:

  1. Patient data collection and evaluation:

Patient data will be collected from patients attending KIMS general surgery and urology OPD, casualty and inpatient department irrespective of age/background/socio economic status. Patient will be evaluated and followed up according to protocol.

  • Detailed history of patient will be entered in proforma.
  • Serum PSA levels will be evaluated first and patients with PSA levels of 4-10 ng/ml only will be taken into the study
  • Free : total PSA ratio will be evaluated.
  • Preliminary ultrasound of abdomen will be done.
  • Patient will be evaluated using TRUS and prostate volume will be calculated.
  • Patient will be informed about the surgical procedure i.e prostatic biopsy via TRUS and consent will be taken.

Volume of the prostate is calculated using the formula

H(height) x W(width)x L(length) x (π/6)

PSAD will be calculated by dividing the PSA levels by volume

Follow up of patients:

Patients will be followed up till treatment is done for the respective disease i.e

For benign disease –TURP

For Ca prostate – Radical prostatectomy/ radiotherapy/ hormonal

therapy

Inclusion criteria:

  • Age › 45yrs with lower urinary tract symptoms
  • PSA levels of 4 – 10 ng/ ml

Exclusion criteria:

Other causes of rasied PSA:

  • Drugs: androgens, finasteride
  • Prostatic manipulation: TURP

PROSTATIC MASSAGE

PROSTATIC BIOPSY

  • Prostatitis
  1. Sample criteria: 30 cases.
  2. Study design: Prospective study.
  3. Sample design: Purposive sampling.
  4. Duration of study: 24 months
  5. Study Place: KIMSHospital, Bangalore.

7.3 Does the study required any investigations or interventions to be conducted on patients? If so, please describe briefly.

Serum PSA levels

Serum free/ total PSA ratio

TRUS

TRUS biopsy

7.4 Has ethical clearance been obtained from your institution, in case of

7.3: YES

  1. List of references:
  1. Benson MC, Whang IS, Pantuck A, Ring K, Kaplan SA, Olsson CA,Cooner WH (1992) Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. J Urol 147:815–816
  2. Yamamoto S, Kin U, Nakamura K, Hamano M, Nishikawa Y,

Takenouchi T, Maruoka M (2005) Transperineal ultrasoundguided12-core systematic biopsy of the prostate for patients witha prostate speciWc antigen level of 2.5–20 ng/mL in Japan. Int JClin Oncol 10:117–121

  1. Sakai I, Harada K, Hara I, Eto H, Miyake H (2004) Limited usefulnessof the free-to-total prostate speciWc antigen ratio for the diagnosisand staging of prostate cancer in Japanese men. Int J Clin Oncol9:64–67
  2. Zhao YR, Xu Y, Zhang D, Chang JW, Zhang SM, Shi QD, Sun G, Han

RF, Yao QX, MaTX (2005) The predictive value of serum prostatespecific antigen, prostate speciWc antigen density and prostatespecific antigen transition zone density in prostate biopsy. Chin JUrol 26:622–625

  1. Allan RW, Sanderson H, Epstein JI (2003) Correlation of minute

(0.5 mm or less) focus of prostate adenocarcinoma on needle biopsywith radical prostatectomy specimen: role of prostate specificantigen density. J Urol 170:370–372

  1. Sözen S, Eskicorapci S, Küpeli B, Irkilata L, Altinel M, Ozer G, UygurC, Alkibay T, Ozen H (2005) Complexed prostate speciWc antigendensity is better than the other PSA derivatives for detection ofprostate cancer in men with total PSA between 2.5 and 20 ng/mL:results of a prospective multicenter study. Eur Urol 47:302–307
  2. Deuk Jae Sung, MD, Sung Bum Cho, MD, Yun Hwan Kim, MD, Comparison of Prostate-Specific Antigen Adjusted for Transition Zone Volume Versus Prostate-Specific Antigen Density in Predicting Prostate Cancer by Transrectal Ultrasonography
  3. Cao XL, Gao JP, Han G, Tang J, Hong BF (2006) Relationship betweenscreening by stratifying cases into groups on prostate specificantigen level and the positive rate of transrectal ultrasoundguided systematic sextant prostate biopsy. Zhonghua Wai Ke ZaZhi 44:372–375
  4. Kurita Y, Ushiyama T, Suzuki K, Fujita K, Kawabe K. PSA value adjusted for the transition zone volume in the diagnosis of prostate cancer. Int J Urol 1996; 3: 367–372
  5. Lin DW, Gold MH, Ransom S, Ellis WJ, Brawer MK. Transition zone prostate specific antigen density: reply by authors. J Urol 1988; 160:82.
  1. Signature of the candidate:
  1. Remarks of the guide:

With respect to the subject of the study i.e prostatic carcinoma, men

with PSA levels of 4-10 ng/ml fall into a “gray zone” where it is difficult to decide whether to go forward with a biopsy. Hence there is a need for a better marker which can clearly indicate the need for biopsy. This study is mainly done to show the utility of PSA density in this “gray zone”

  1. Name and designation of:

a)Guide: Dr Sudarshan Babu

Professor

Dept. of general surgery

KIMSHospitalBangalore

Signature:

b)Head of the department: Prof. Dr. Satish. V

Head of DepartmentSurgery

KIMS HospitalBangalore

Signature:

Remarks:

c)Chairman and principal:

Signature: