Avi Stein

Prostate Specific Antigen Levels After Radical Prostatectomy in Patients with Organ Confined and Locally Extensive Prostate Cancer

A total of 230 patients with localized prostate cancer underwent radical retropubic prostatectomy at UCLA (pathological stage T1-3 N0, M0). Classification into groups included 115 patients with organ confined disease (group 1), 82 with invasion into or through the capsule (group 2) and 33 with seminal vesicle involvement (group 3). Median followup was 48 months. The 10-year, cause-specific survival was 96%, 90% and 63%, and 5-year, clinical, disease-free survival was 91%, 79% and 58% for the 3 groups, respectively. Recent prostate specific antigen (PSA) levels were measured in most patients, even those operated upon many years ago. Of the patients 41 had detectable (0.4 ng./ml. or greater) PSA levels without any other clinical evidence of progression and 15 with clinical evidence of progression had PSA levels in the detectable range at the time of clinical progression. When isolated detectable PSA was also considered an indicator of progression the 5-year and 10-year, disease-free rates were 61% and 41%, respectively. These data show that radical prostatectomy performed in patients with even microscopic invasion into the capsule, positive margins and seminal vesicle involvement is associated with a higher clinical progression rate than organ confined disease. If isolated detectable PSA is also considered an indicator of recurrence the disease-free survival after radical prostatectomy might be less than indicated by previous studies. The relationship among survival, local tumor extension and PSA must be carefully examined.

Prognosis of Patients with Stage D1 Prostate Carcinoma Following Radical Prostatectomy with and Without Early Endocrine Therapy

Early endocrine therapy after radical retropubic prostatectomy was compared to radical prostatectomy alone (nonearly endocrine therapy) for the treatment of carcinoma of the prostate with lymph node metastases. Our retrospective analysis demonstrated that the 2 cohorts were similar with respect to patient age, Gleason sum score, seminal vesicle invasion, lymph node involvement, tumor volume and pathological stage of the primary tumor. The cause-specific survival of the entire group was 84% at 60 months and 78% at 98 months. The cause-specific curves for the early and nonearly endocrine therapy group were not significantly different (p less than 0.194), although the estimated 9-year survival rates were 91 and 71%, respectively. Survival free of disease was significantly prolonged in the early endocrine therapy group (p less than 0.030), with a 9-year estimated rate free of disease of 67% versus 32% in the nonearly endocrine therapy group. Followup prostate specific antigen serum levels were analyzed and the value as a progression marker is discussed. These data suggest that a radical operation plus early endocrine therapy is effective palliation in selected patients with low volume lymph node metastases, producing clinical survival free of disease in most patients.

Neoadjuvant Hormonal Deprivation in Patients with Locally Advanced Prostate Cancer

A total of 22 patients with locally advanced prostate cancer (stage B2 to C) was entered into a protocol for 3 months of preoperative hormonal deprivation. Of the patients 8 were judged to have clinical stage B2 and 14 to have stage C disease. The protocol regimen consisted of daily administration of flutamide (250 mg. orally 3 times per day) and leuprolide injection (7.5 mg. intramuscularly) every month. Patients with objective evidence of downstaging by prostate specific antigen (PSA) levels and transrectal ultrasound were offered surgical therapy. Of the 22 patients 20 have completed the protocol and are evaluable, and 2 of them did not show significant downstaging and elected radiotherapy. Preoperative hormonal therapy produced an average 33% downsizing of the prostate gland as determined by transrectal ultrasound volumetrics. Decreases in serum PSA values were demonstrated from a pre-hormonal average of 30 micrograms./l. (range 0.7 to 97.7) to an average of 0.53 micrograms./l. (range 0.2 to 5.7) after hormonal therapy. Of the 18 patients who underwent an operation after demonstrating significant downsizing 7 had pathologically confirmed stage B disease, 7 had stage C cancer and 4 had positive pelvic lymph nodes. Of the 8 clinical stage B2 cancer patients 3 had pathological stage B2 disease following the protocol. Of the 12 clinical stage C cancer patients 3 had pathological stage B disease, 4 had positive pelvic lymph nodes and the remainder had pathological stage C cancer. Thus, only 3 of 20 patients (15%) demonstrated pathological downstaging from the clinical stage. Downsizing the prostate volume and PSA changes with hormonal therapy were not predictive of patient outcome either alone or in combination. Preoperative hormonal therapy did not appear to facilitate the surgical procedure. Patients completing neoadjuvant hormonal therapy had an average estimated blood loss of 1,238 ml. and an average operating time of 183 minutes. A group of 20 consecutive patients with stage B2 prostate cancer who underwent radical prostatectomy without preoperative hormone therapy had an average estimated blood loss of 1,296 ml. and an average operating time of 171 minutes.

Adjuvant radiotherapy in patients post radical prostatectomy with tumor extending through capsule or positive seminal vesicles

Between 1976 and 1989, 115 patients at UCLA had radical retropubic prostatectomy for clinically localized prostate cancer with positive surgical margins, penetration of tumor into or through the capsule, or positive seminal vesicles. Twenty-four of those received adjuvant radiotherapy after having recovered from surgery. Complications of adjuvant treatment were uncommon and included urethral strictures in 3 patients and transient leg edema in 1. No patient in this group has had proved clinical disease progression though 6 have isolated detectable serum prostate-specific antigen (PSA) values. Clinical disease-free survival at five and seven years was 92 percent. If detectable PSA is also considered as evidence of tumor recurrence, the corresponding disease-free survival rates were 75 percent at five years and 54 percent at seven years. The 91 patients who received no postoperative radiotherapy had a clinical disease-free survival of 67 percent at five years and 56 percent at seven years. Disease-free survival drops to 43 percent and 24 percent, respectively, if detectable follow-up PSA is considered an indicator of disease progression. The comparisons of the survivorship curves in this retrospective study for the two treatment groups are statistically significant both for disease-free survival (p = 0.041), and disease-free survival with undetectable PSA (p = 0.043). Adjuvant radiotherapy has a beneficial effect after radical prostatectomy in patients with local tumor extension.

Detection of local recurrence after radical prostatectomy by prostate specific antigen and transrectal ultrasound

Twenty patients with detectable levels of prostate specific antigen (PSA) after radical prostatectomy with no identifiable distant metastases were evaluated for local recurrence by digital rectal examination and transrectal ultrasound combined with biopsies. Of the patients 9 (45%) were found to have histological evidence of local recurrence at the initial assessment. All 4 patients with an abnormal digital rectal examination had recurrent disease. Transrectal ultrasound displayed abnormalities in 12 of the 20 patients, 7 of whom had positive biopsies. Random biopsies of the vesicourethral junction were performed in 8 patients who had negative ultrasound findings and an unremarkable digital rectal examination, of whom 2 had histological documentation of local recurrence. Complications occurred in 1 patient (5%) who presented with clot retention. We conclude that PSA is an excellent tool for identification of recurrent disease after radical prostatectomy, and transrectal ultrasound guided biopsy is a useful diagnostic approach in patients suspected of local failure, especially when the digital rectal examination is unremarkable.

Salvage radical prostatectomy after failure of curative radiotherapy for adenocarcinoma of prostate

Radical prostatectomy with curative intent was performed in 13 patients with prostate cancer after local failure of radiotherapy. Of these patients, 2 underwent cystoprostatectomy for bladder neck involvement by the prostatic tumor. Local recurrence had been diagnosed twenty-one to one hundred sixty-eight months (mean 65.4 months) after completion of radiotherapy (6,000-7,000 cGy; mean 6,136 cGy). Three patients had radioactive implants. Rising prostate-specific antigen (PSA) was part of the indication for surgery in 5 patients. Complications included minor rectal injury (1 patient) and total incontinence (2/13 patients). Two patients had positive surgical margins and 6/13 patients had involvement of seminal vesicles, 2 of whom also had positive lymph nodes. The authors conclude that salvage prostatectomy is feasible after radiation failure. Transrectal ultrasound and careful monitoring of PSA after irradiation treatment may improve patient selection and minimize the risk of complications and incomplete excision.

Hyperbaric oxygen therapy for radiation-induced haemorrhagic cystitis

To assess the efficacy of hyperbaric oxygen (HBO) for treating haemorrhagic cystitis.

Telomerase activity and cytokeratin 20 as markers for the detection and followup of transitional cell carcinoma: an unfulfilled promise.

PURPOSEnTelomerase activity compensates for the erosion of chromosomes and it has been detected in a wide variety of human tumors. Cytokeratin 20, an intermediate filament of epithelial cells, is expressed particularly in the urinary tract. These 2 molecules are candidates to become markers for the detection and followup of bladder carcinoma. We evaluate whether each molecule may serve as a potential marker and whether the 2 combined would improve the detection or followup of bladder carcinoma in a noninvasive manner.nnnMATERIALS AND METHODSnWe obtained 44 morning urine samples from patients with transitional cell carcinoma patients and 26 from age matched patients with a wide variety of clinical disorders but no malignancy of any kind. A telomerase polymerase chain reaction-enzyme-linked immunosorbent assay kit was used to determine telomerase activity and cytokeratin 20 expression was determined by nested reverse transcriptase-polymerase chain reaction.nnnRESULTSnAll samples tested positive for cytokeratin 8 expression, which verified epithelial cells in the urine samples. Of the 44 transitional cell carcinoma cases of all stages and grades 37 (84.1%) were positive for telomerase activity, 36 (81.8%) were positive for cytokeratin 20 expression and 65.9% were double positive. Of the 29 controls with various clinical conditions other that malignancy 22 (75.9%) were positive for telomerase activity, 13 (44.83%) were positive for cytokeratin 20 expression and 34.6% were double positive.nnnCONCLUSIONSnTelomerase activity and cytokeratin 20 expression are not specific for malignancy and may be detected in many nonmalignant pathological conditions. Therefore, their use as potential markers of bladder carcinoma should be carefully reevaluated.

Sonographic Detection of a Foreign Body in the Urethra and Urinary Bladder

Reported herein is a 41-year-old male who presented for ultrasound due to two episodes of lower urinary tract infections within a period of 5 months. The sonographic examination revealed an elongated foreign body in the urethra extending into the urinary bladder. Self-insertion of foreign bodies into the urethra is usually done for erotic stimulation. However, foreign bodies can be inserted by children due to curiosity and by mentally retarded people, patients with psychiatric disorders as well as by intoxicated patients and in confusional states. Due to embarrassment, the patients seek medical help only when they are symptomatic and hence some of the foreign bodies are removed only several months after insertion. Detection might be either by plain abdominal films when the foreign bodies are radiopaque or by the use of contrast media. In the case presented by us, this was done by sonography. Endoscopic removal of these foreign bodies is considered the treatment of choice. Recurrent or chronic unexplained urinary tract infections should raise a high index of suspicion to the possible existence of a foreign body in the urethra and/or urinary bladder.

Telomerase activity in patients with transitional cell carcinoma

Telomerase activity is not detectable in normal cells, and their telomers shorten until the chromosome is unable to replicate. Immortal cells have short but stable chromosomes and increased telomerase activity. Transitional cell carcinoma (TCC) has only a few useful markers of diagnostic or prognostic importance. The objective of this study was to determine whether there was a correlation between telomerase activity and the grade or stage of TCC, and whether the enzymes activity could serve as a biochemical marker of this tumor.