CRYOSURGICAL ABLATION OF PROSTATE CANCER: PATTERNS OF CANCER RECURRENCE

Purpose

We determined the rate of biochemical and biopsy failure in relation to the prostate specific antigen (PSA) nadir, the effect of neoadjuvant androgen blockade and the pattern of residual tumor after cryosurgical ablation of prostate cancer.

Materials and Methods

From July 1993 to April 1996, 134 patients underwent 147 cryosurgical ablation procedures. Of those patients, 110 had adequate followup and did not receive post-treatment androgen deprivation. Followup included PSA determination at 3, 6 and 12 months, and every 6 months thereafter. Biopsies were performed at 6 months or with biochemical failure defined as PSA nadir 0.5 ng./ml. or greater or subsequent biochemical failure (PSA increase 0.2 ng./ml. or greater). Biochemical and biopsy failures were correlated with PSA nadir values following cryosurgery (less than 0.1 ng./ml., 0.1 to 0.4 and or greater 0.5). A total of 68 patients had careful ultrasound guided mapping biopsy preoperatively and postoperatively to define the sites of disease. The likelihood of residual disease was correlated with the initial site(s) of the cancer in an attempt to identify if areas of the prostate and/or seminal vesicles were more likely to be sites of treatment failure.

Results

At a mean followup of 17.6 months biochemical failure (subsequent rise in PSA 0.2 ng./ml. or greater) was lowest in those who achieved PSA nadirs less than 0.1 ng./ml. (21%) but it was noted in 48% of patients with nadirs between 0.1 and 0.4 ng./ml. Those patients with PSA nadirs 0.5 or greater had either immediate local failure (46%), subsequent local or biochemical failures (43%) or extremely high PSA nadirs (greater than 30 ng./ml.) necessitating hormonal therapy (11%). Biopsy failure was lowest in those with nadirs less than 0.1 ng./ml. (7%) and those with nadirs 0.1 to 0.4 ng./ml. (22%). In contrast, 60% of the patients with nadir values 0.5 ng./ml. or greater had biopsy failure. Biochemical and biopsy failure tended to occur within the first 18 months after treatment. Neoadjuvant androgen blockade appeared to reduce subsequent biochemical failure in patients with stages T1 and T2 cancers (11% versus 50% in those without androgen deprivation) but not in those with T3 and T4 cancers. Recurrence was more common in cancers at the apex (9.5%) and seminal vesicles (44%), in contrast to those located in the mid gland (4%) and base (0%).

Conclusions

A PSA nadir of 0.4 ng./ml. or less should be achieved following cryotherapy. Higher values are associated with a significant risk of continued PSA elevation and a high likelihood of residual disease detected on prostatic biopsy. Local failure tends to occur at the apex and seminal vesicles. Neoadjuvant androgen blockade reduces the risk of biochemical failure in patients with stages T1 and T2 cancers.     

PREDICTIVE VALUE OF PROSTATE SPECIFIC ANTIGEN NADIR AFTER SALVAGE CRYOTHERAPY

Purpose

We determined nadir prostate specific antigen (PSA) after salvage cyrotherapy to distinguish patients who are potentially cured from those at risk for subsequent biochemical and biopsy proved failure.

Materials and Methods

A total of 146 patients who underwent salvage cyrotherapy were followed a median of 21 months (range 3 to 47) with regular serum PSA analysis and digital rectal examination. Sextant biopsies were performed at 6 months or earlier when PSA increased greater than 2 ng./ml. from the nadir value (biochemical failure) or there was a palpable local recurrence. We compared the incidence of biochemical failure and biopsy specimens positive for cancer to pretreatment PSA and posttreatment nadir PSA.

Results

In 59 of the 146 patients (40%) PSA decreased to an undetectable level within a median of 3 months. In 85 of the 109 patients (78%) who underwent biopsy the specimens were negative for cancer. Low serum PSA nadir values were associated with low pretreatment PSA and a low incidence of biochemical failure. In 6 of 60 patients (10%) in whom PSA nadir was 0.5 ng./ml. or less and in 18 of 49 (37%) with a higher PSA nadir biopsy was positive for cancer.

Conclusions

A PSA nadir of 0.5 ng./ml. or less should be achieved after salvage cryotherapy. Higher nadirs are more likely to be associated with increasing posttreatment PSA and positive biopsies. PSA nadir is a better prognostic indicator of biochemical and biopsy proved failure after salvage cryotherapy than pretreatment PSA.     

Salvage cryotherapy using an argon based system for locally recurrent prostate cancer after radiation therapy: the Columbia experience

PURPOSE: Cryosurgical ablation of the prostate has been reported as potential treatment for radioresistant clinically localized prostate cancer. We report our experience with the safety and efficacy of salvage cryosurgery using the argon based CRYOCare system (Endocare, Inc, Irvine, California). MATERIALS AND METHODS: Between October 1997 and September 2000, 38 men with a mean age of 71.9 years underwent salvage cryosurgery for recurrent prostate cancer after radiation therapy failed. All patients had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. Subsequently prostate biopsy was positive for cancer. Pre-cryosurgery bone scan demonstrated no evidence of metastatic disease. In addition, these patients received 3 months of neoadjuvant androgen deprivation therapy before cryotherapy. RESULTS: The PSA nadir was 0.1 or less, 1 or less and greater than 1 ng./ml. in 31 (81.5%), 5 (13.2%) and 2 (5.3%) patients, respectively. Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years. Reported complications included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9% and scrotal edema in 10.5%. The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%. CONCLUSIONS: Our study supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails. Using the CRYOCare machine resulted in a marked decrease in complications.     

Time to achieve a prostate specific antigen nadir of 0.2 ng./ml. after simultaneous irradiation for prostate cancer

PURPOSE: A prostate specific antigen (PSA) cutoff point of 0.2 ng./ml. has been suggested as the standard definition of disease freedom for curative treatment of localized prostate cancer. The time to achieve this goal after irradiation was determined in this study. MATERIALS AND METHODS: From August 1992 to December 1996, 539 consecutive men with clinical stage T1T2NX prostate cancer who had a minimum 5-year PSA followup and achieved a PSA nadir of 0.2 ng./ml. without hormones were evaluated. All patients were treated with simultaneous irradiation with a transperineal prostate iodine implant, followed by external beam irradiation. Time to achieve a PSA of 0.2 ng./ml. was retrospectively calculated from the date of implantation in all men and according to various factors. Recurrence was defined as a subsequent increase above a PSA of 0.2 ng./ml. Minimum followup was 5 years (median 6.5, range 5 to 9). RESULTS: In all 539 men the median time to a PSA nadir of 0.2 ng./ml. was 27 months, while 534 (99%) achieved this level by 60 months of followup. Median time to achieve this PSA goal was 20 and 39 months in patients without and with a PSA bounce, respectively. Pretreatment PSA, disease status and ultimately PSA bounce, Gleason score and stage had little or no effect on time to a PSA of 0.2 ng./ml. CONCLUSIONS: With rare exceptions to be potentially cured of prostate cancer by simultaneous irradiation men must achieve a PSA nadir of 0.2 ng./ml. within 5 years of implantation. Failure to reach this goal by 60 months of followup almost always indicates persistent disease.     

Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer

PURPOSE: We determine whether the nadir prostate specific antigen (PSA) level after hormone therapy can be used to predict the progression to hormone refractory prostate cancer. MATERIALS AND METHODS: We reviewed the progressive status and survival of 177 patients with stage C or D prostate cancer who had received hormone therapy at our institution. The overall survival rate, incidence of progression to hormone refractory prostate cancer and interval until progression were analyzed with reference to the nadir PSA level. Multiple regression analysis was used to analyze the predictive factors for progression to hormone refractory prostate cancer, and the relative efficacy of the nadir PSA level in predicting progression was evaluated by receiver operating characteristics analysis. RESULTS: Median followup was 39 months (range 3 to 89) and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had progression to hormone refractory prostate cancer. Median time until nadir PSA levels were reached after hormone therapy was 8.1 months and median time until hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10 ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar clinicopathological characteristics. Nadir PSA levels correlated significantly with pretreatment PSA levels, Gleason scores and progression to hormone refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and inversely correlated with the interval to the establishment of hormone refractory prostate cancer (r = -0.465, p <0.05). By univariate analysis bone metastasis, nadir PSA, PSA at 6 months after treatment and pretreatment PSA were significantly associated with progression to hormone refractory prostate cancer. Only the nadir PSA was calculated to be an independent factor by multivariate analysis. Receiver operating characteristics analysis indicated that nadir PSA predicted progression to hormone refractory prostate cancer after 2 years with an accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1 ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an independent prognosticator for survival, as were initial levels of hemoglobin and alkaline phosphatase. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.     

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.     

The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng./ml.) in predicting prostate cancer: is biopsy always required?

PURPOSE: Urologists are often referred patients who initially present with an extremely high serum prostate specific antigen (PSA) level. Despite a presumptive diagnosis of prostate cancer, many of these men undergo biopsy to obtain a tissue diagnosis before treatment with androgen ablative therapy. We examined a data base of men undergoing prostate biopsy to determine the accuracy of high PSA levels (greater than or equal to 20 ng./ml.) in predicting prostate cancer. MATERIALS AND METHODS: We reviewed the records of 1,250 consecutive patients undergoing transrectal ultrasound guided prostate biopsy at 1 institution. From this data base we identified all patients with PSA greater than or equal to 20 ng./ml. at the time of prostate biopsy. The accuracy of PSA in predicting cancer was determined by calculating positive predictive values for PSA ranges and PSA cutoffs. RESULTS: We identified 187 men (15%) presenting with PSA greater than or equal to 20 ng./ml. Of these 187 men 157 (84.0%) were diagnosed with prostate cancer on initial biopsy. Due to a negative initial biopsy, yet a high suspicion of cancer, 12 (6.4%) patients underwent at least 1 repeat biopsy. Of these 12 men 6 (50%) were diagnosed with cancer on repeat biopsy. Overall, 163 of the 187 men (87.2%) were diagnosed with prostate cancer by biopsy. Stratified by PSA ranges, positive predictive values were 73.6% for 20 to 29.9, 90.3% for 30 to 39.9, 93.8% for 40 to 49.9, 100% for 50 to 99.9, 95% for 100 to 199.9 and 100% for greater than or equal to 200 ng./ml. Using PSA cutoffs positive predictive values were 95.7% for PSA greater than or equal to 30, 97.6% for PSA greater than or equal to 40 and 98.5% for PSA greater than or equal to 50 ng./ml. CONCLUSIONS: Serum PSA, when increased above 50 ng./ml., is 98.5% accurate in predicting the presence of prostate cancer on tissue biopsy. Nonetheless, since transrectal prostate biopsy has a low complication rate and is relatively well tolerated, we recommend continuing to biopsy most patients with high PSA levels. However, carefully selected elderly patients on chronic anticoagulation, with severe co-morbidities or presenting with spinal cord compression may not require biopsy before androgen ablative therapy since PSA is highly accurate in diagnosing prostate cancer at levels greater than 50 ng./ml.     

PSA elevation during prostate cryosurgery and subsequent decline

PURPOSE: To determine the immediate effect of prostate cryosurgery on PSA and the subsequent decline. METHODS AND MATERIALS: PSA level was measured in 14 patients who underwent cryosurgery for prostate cancer. Blood samples were taken immediately before and after cryosurgery and 1, 2, 4, 6 weeks and 3 months postoperatively. A confidence interval for the elevation from baseline to maximal PSA was calculated. PSA decline was assessed in patients with a nadir PSA < or =0.5 ng/mL. Patients with a postoperative nadir PSA >0.5 ng/mL were considered to harbor viable cancer and were excluded from the decline analysis. The observed PSA levels during the postoperative period were compared with the expected levels that were calculated according to the maximal PSA level and a serum half-life of 2.5 days. Student t-test was used to compare expected and observed PSA levels. RESULTS: PSA increased from an average of 9.23 ng/mL preoperatively to a maximum average of 155 ng/mL (maximal PSA ranges: 18.9-490.5 ng/mL). The 95% CI for the increase in PSA from baseline level was 63.4 to 224.14. PSA nadir < or =0.5 ng/mL was achieved in 10 patients. The observed PSA decline course was slower than expected according to its half-life. Average observed and expected PSA levels at 2,4 and 6 weeks after cryosurgery were 10.4 versus 3.57 ng/mL (P = 0.005), 0.65 versus 0.07 (P = 0.007) and 0.09 versus 0.001 (P = 0.03), respectively. CONCLUSION: PSA levels increase steeply following cryosurgery, and decline slower than expected according to the serum half-life.     

Treatment of chronic prostatitis lowers serum prostate specific antigen

PURPOSE: We evaluated men with documented chronic prostatitis and elevated serum prostate specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs lowers serum PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 95 men who presented with serum PSA greater than 4 ng./ml. and were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions. Patients meeting these criteria were treated with a 4-week course of antibiotics and a nonsteroidal anti-inflammatory agent. In all patients followup PSA was determined within 2 months of treatment. RESULTS: Mean PSA decreased 36.4% from 8.48 ng./ml. before to 5.39 after treatment (p <0.001). In 44 patients (46.3%) serum PSA decreased to below 4 ng./ml. (mean 2.48) and these patients no longer had an indication for biopsy. In the remaining 51 patients serum PSA remained elevated at greater than 4 ng./ml. and they underwent double sextant transrectal ultrasound guided biopsy. Pathological study showed prostate cancer in 13 cases (25.5%), chronic inflammation in 37 (72.5%) and only benign prostatic hypertrophy in 1 (1.05%). PSA in the 13 patients with prostate cancer decreased with treatment only 4.8% from 8.32 to 7.92 ng./ml. (p >0.05). Followup PSA at a mean of 11.4 months was determined in 19 of the 44 men who responded to treatment. Mean PSA increased only 4.5% from 2.35 to 2.46 ng./ml. (p >0.05) during this followup interval. CONCLUSIONS: In almost half of the patients diagnosed with elevated PSA and chronic prostatitis serum PSA normalized with treatment and there was no longer an indication for transrectal ultrasound guided biopsy. Our study suggests that chronic prostatitis is an important cause of elevated PSA and when it is identified, treatment can decrease the percent of negative biopsies.     

Prostate specific antigen nadir following external beam radiation therapy for clinically localized prostate Cancer: The relationship between nadir level and disease-free survival

Purpose

We determined whether the prostate specific antigen (PSA) nadir achieved following external beam radiation therapy alone predicts biochemical disease-free survival in a large cohort of men with clinically localized prostate cancer.

Materials and Methods

Between January 1986 and October 1993, 364 men with clinically localized, stages T1 to T3 adenocarcinoma of the prostate received definitive external beam radiation therapy with no prior, concomitant or adjuvant endocrine therapy. PSA was measured before treatment in 326 men (90 percent) and serial PSA was measured following treatment in all patients. All men were followed continuously for at least 24 months (median 44 months, range 24 to 90, mean 46). Biochemical failure after irradiation was defined as PSA of 1.5 ng./ml. or more and 2 consecutive serum PSA elevations.

Results

The 5-year overall biochemical disease-free survival rate for the entire group was 56 percent. PSA nadir was predictive of subsequent biochemical disease-free survival. The biochemical disease-free survival rate at 3 years was 93, 49 and 16 percent for PSA nadirs of 0 to 0.99, 1 to 1.99 and 2 or more ng./ml., respectively (p = 0.0001). In a multivariate analysis PSA nadir (0 to 0.99 versus 1.0 to 1.99 versus 2 or more ng./ml.) was an independent predictor of biochemical disease-free survival along with pretreatment PSA, central axis dose, Gleason grade and T stage.

Conclusions

PSA nadir after radiation therapy is an indicator of subsequent biochemical disease-free survival. Patients who achieve a nadir of less than 1 ng./ml. following external beam radiation therapy have a favorable biochemical disease-free survival rate, while those with a nadir of greater than 1 ng./ml. have a high subsequent failure rate. Strategies to improve results should focus on techniques to increase the likelihood of achieving a PSA nadir of less than 1 ng./ml.     

A standard definition of disease freedom is needed for prostate cancer: undetectable prostate specific antigen compared with the American Society of Therapeutic Radiology and Oncology consensus definition

PURPOSE: Freedom from prostate cancer is defined by undetectable prostate specific antigen (PSA) after surgery and the American Society of Therapeutic Radiology and Oncology (ASTRO) criteria are recommended for irradiation. Whether these definitions of disease freedom are comparable was evaluated in this study. MATERIALS AND METHODS: From August 1992 to August 1996 simultaneous irradiation with prostate 125iodine implantation followed by external beam irradiation was performed in 591 consecutive men with stage T1T2NX prostate cancer. All patients had a transperineal implant and none received neoadjuvant hormones. Disease freedom was defined by a PSA cutoff of 0.2 ng./ml. and the ASTRO consensus definition. Median followup was 6 years (range 5 to 8). RESULTS: Of the 591 men in this study 65 had recurrence by ASTRO criteria and 93 had recurrence by a PSA cutoff of 0.2 ng./ml., which was a significant difference (p = 0.001). On multivariate analysis of the factors related to disease-free status the definition of disease freedom, pretreatment PSA and Gleason score were highly significant. Of the 528 men with a minimum 5-year PSA followup the 8-year disease-free survival rate by ASTRO criteria was 99% in those who achieved a PSA nadir of 0.2 ng./ml. and 16% in those with a nadir of 0.3 to 1 ng./ml. Of the 469 disease-free patients by ASTRO criteria with a minimum 5-year followup 455 (97%) achieved a PSA nadir of 0.2 ng./ml. or less. CONCLUSIONS: The definition of freedom from prostate cancer significantly affects treatment results. A standard definition is needed and a PSA cutoff of 0.2 ng./ml. is suggested as the standard for all curative treatments for localized prostate cancer.     

Cryosurgery in the management of prostate cancer

This article reviews the current status of the prostatic cryosurgery in the management of patients with prostate cancer. Recent advances in cryoablative technology have allowed to treat these patients successfully with decreased morbidity. Using transrectal high-resolution ultrasound imaging, prostate cryotherapy is delivered with multiple ultrathin (17-gauge) cryo-needles, via percutaneous transperineal approach. The extent of freezing can be precisely controlled and monitored with thermic devices, tissue destruction is monitored with real-time visualization of the prostate and surrounding structures, and urethral warming is used to avoid urethral sloughing. However, the results with the second and third-generation cryosurgical equipment will have to be confirmed by means of prospective and randomized trials, because up to now we only have data based on retrospective analyses, which are very heterogeneous. The ability of prostate-specific antigen (PSA) to predict long-term outcome after cryotherapy for localized prostate cancer is not well known because experience with this treatment modality is still limited; however, it seems that a PSA value of 0.5 ng/ml or less after 6 months or longer after cryotherapy would be associated with a high probability (greater than 95%) of negative post-treatment biopsy. Cryosurgery could also be an option of treatment for men with recurrent local disease who have undergone radiotherapy or radical prostatectomy. We have to keep in mind possible complications (incontinence, impotency, urethrorectal fistula or bladder outlet obstruction. The favorable side effect profile and preliminary oncologic and funtional results could suggest that cryosurgery will have a role in the minimally invasive management of selected patients with prostate cancer.     

冷冻治疗单病灶前列腺癌12例临床分析

目的 评价冷冻疗法治疗局限性单病灶前列腺癌的近期疗效及安全性。 方法 局限性单病灶前列腺癌患者12例,均经穿刺活检证实。术前PSA 4.2～14.9 ng/ml,平均9.7 ng/ml。Gleason评分5分3例,6分5例,7分4例。临床分期T1c期8例、T2a期4例。均行超声引导下经会阴前列腺局灶冷冻治疗。术后1年内每3个月、以后每6个月复查PSA。PSA最低值≥1.0 ng/ml或PSA达最低值后上升＞2.0 ng/ml者再次行前列腺穿刺活检排除肿瘤复发。 结果 12例手术顺利,手术时间( 82±26) min,均未输血。术后住院(5±2)d。拔除尿管后,12例控尿均满意。术前有勃起功能者10例,术后仍保持勃起功能者8例。12例随访12 ～ 30个月,平均23个月。术后PSA最低值0.1～6.8 ng/ml,平均2.2 ng/ml,其中＜1.0 ng/ml者9例。术后PSA异常行前列腺穿刺活检4例,阴性3例,冷冻对侧腺体活检阳性1例。 结论 超声引导下经会阴前列腺局灶冷冻治疗安全有效、并发症少,可用于局限性单病灶前列腺癌患者,远期疗效尚需进一步观察。     

Cryoablation for clinically localized prostate cancer using an argon-based system: complication rates and biochemical recurrence

OBJECTIVE: To determine the complication rates and biochemical recurrence after cryoablation of the prostate, using an argon gas-based system, in patients with localized prostate cancer. PATIENTS AND METHODS: Between October 1997 and June 1999, 35 patients underwent cryoablation of the prostate (19 after radiation therapy failure and 16 as a primary treatment for localized prostate cancer). All patients had biopsy-confirmed prostate cancer with no seminal vesicle invasion, negative bone scans and a negative lymph node dissection. Patients received 3 months of combined hormonal therapy before cryosurgery. One surgeon performed all the procedures. Biochemical recurrence was defined by an increase in prostate specific antigen (PSA) of >/= 0.2 ng/mL above the PSA nadir. RESULTS: The complications were rectal pain (26%), urinary infection (3%), scrotal oedema (12%), haematuria (6%) and incontinence (6%). Complication rates were higher in those patients who failed after radiation therapy than in those who did not receive radiation (incontinence 11% vs 0%, rectal pain 37% vs 12%) but the difference was not statistically significant. Twenty-two patients (63%) had an undetectable serum PSA nadir (< 0.1 ng/mL) after cryotherapy and 30 (84%) patients had a PSA value of < 1.0 ng/mL. After a mean follow-up of 8.3 months (range 0.2-18), nine patients had biochemical recurrence. The biochemical recurrence-free survival (BRFS) was 70% at 9 months. Patients who had an undetectable PSA nadir had a statistically higher BRSF at 9 months than did patients who had a detectable PSA nadir (89% vs 55%, respectively, P = 0.03). Similarly, patients with a preoperative serum PSA level of < 10 ng/mL had a statistically higher BRFS than patients who had a PSA level of > 10 ng/mL (86% vs 42% at 9 months, P < 0.001). CONCLUSION: A PSA level before cryotherapy of < 10 ng/mL and an undetectable PSA nadir after cryotherapy were associated with the highest BRFS. Cryoablation of the prostate, with low morbidity, seems to be a viable option in managing patients by salvage therapy after radiation therapy and for the primary treatment of clinically localized prostate cancer.     

Prostate specific antigen levels after definitive irradiation for carcinoma of the prostate.

Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined.     

PRELIMINARY OUTCOMES FOLLOWING CRYOSURGICAL ABLATION OF THE PROSTATE IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CARCINOMA

Purpose

Cryosurgical ablation of the prostate is a novel therapeutic modality that induces cell lysis in the prostate by direct application of low temperatures. We have been conducting an ongoing prospective pilot study of the use of cryosurgical prostate ablation in treating patients with nonmetastatic prostate adenocarcinoma since January 1993. Results in 145 consecutive patients with mean 36 months and minimum 12 months of followup are presented.

Materials and Methods

Accrual was open to patients with clinical stages T1a to T3c prostate adenocarcinoma. Pelvic lymph node dissections were recommended but not required for patients with prostate specific antigen (PSA) greater than 15 ng./ml. before study entry. PSA changes, random prostate biopsy findings and morbidities after cryosurgical prostate ablation were recorded for each patient.

Results

Overall actuarial rates at 42 months for maintaining PSA less than 0.3 and less than 1.0 were 59% and 66%, respectively. The overall actuarial progression-free rate at 60 months was 56%. Among 160 biopsies performed 16% showed some evidence of residual carcinoma. Overall crude rates of maintaining either a negative biopsy or PSA less than 0.3 at 6 and 24 months after cryosurgical prostate ablation were 87% and 73%, respectively. Significantly higher morbidities were seen in previously radiated patients undergoing cryosurgical prostate ablation compared to those with no prior radiation. Among nonradiated patients 85% experienced no significant morbidity after cryosurgical prostate ablation.

Conclusions

Although preliminary, short-term outcomes after cryosurgical prostate ablation appear to be comparable to identical outcomes reported for external beam radiotherapy. Based on these results cryosurgical prostate ablation appears to be an effective therapeutic alternative for treating patients with localized prostate adenocarcinoma.     

Cancer Diagnosis with Prostate Specific Antigen Greater than 10 ng./ml. and Negative Peripheral Zone Prostate Biopsy

Purpose

We assessed the results of additional diagnostic procedures in men with prostate specific antigen (PSA) more than 10 ng./ml. and a peripheral zone prostate biopsy negative for cancer.

Materials and Methods

A total of 68 men with PSA more than 10 ng./ml. and a peripheral zone biopsy negative for cancer was investigated with 1 or more peripheral zone biopsies (17), prostatectomy (18), or 1 or more peripheral zone biopsies and needle biopsy of the transition zone or prostatectomy (33).

Results

Cancer was detected in 20 of 68 patients (29 percent) with 1 or more additional diagnostic procedures. Of 51 patients whose transition zone was biopsied or who underwent prostatectomy 16 had cancer, and in 8 the malignancy appeared to be isolated to the transition zone. Mean PSA density and proportion of patients with PSA density more 0.15 were significantly greater and mean prostate volume was significantly less in the 20 patients with compared to 31 without identifiable cancer.

Conclusions

At least 30 percent of men with PSA more than 10 ng./ml. and a negative peripheral zone biopsy have prostate cancer. In approximately 50 percent of cases the cancer appears to reside in the transition zone, and transition zone biopsy or prostatectomy is required for diagnosis.     

Biopsy after external beam radiation therapy for adenocarcinoma of the prostate: correlation with original histological grade and current prostate specific antigen levels.

We obtained post-irradiation biopsies in 37 men with initially stage T3 prostatic adenocarcinoma treated by external beam radiotherapy. Eligibility for post-irradiation biopsy included no clinical local failure, interval since treatment of 24 months or more and no endocrine therapy. Of the 37 patients 23 (62%) had negative biopsies while 14 (38%) had positive biopsies. Of 23 patients whose original cancer was well or moderately differentiated 18 (78%) had negative biopsies, compared to only 5 of 14 (36%) of those with poorly differentiated cancer (p less than 0.03). Among 19 patients whose current serum prostate specific antigen (PSA) value is less than 2.5 ng./ml. 15 (79%) had negative biopsies, compared to only 4 of 14 (29%) with a PSA level of greater than 2.5 ng./ml. (p less than 0.02). These results strongly suggest that there is a low probability of positive post-irradiation biopsy regardless of its significance in men with a normal prostate by palpation and a normal serum PSA value. However, short followup since biopsy precludes analysis of the predictive value of post-irradiation biopsy on long-term local and distant disease status.     

前列腺癌ADT治疗期间PSA最低值的评估及临床意义

目的:探讨PSA最低值在前列腺癌雄激素剥夺治疗(ADT)中的临床意义.方法:回顾性分析1999年6月～2007年6月间采用双侧睾丸切除术治疗71例前列腺癌患者的临床资料,按照治疗后PSA最低值可否达到0.2 ng/ml为界,将患者分为两组,并作多参数比较.结果:诊断时平均年龄76.0(56～90)岁.双侧睾丸切除术后随访时间(43.9±27.8)个月,45例(63.4%)患者的PSA最低值≤0.2 ng/ml,26例(36.6%)>0.2 ng/ml,两组平均PSA最低值差异有统计学意义(P<0.002).两组患者达到PSA最低值的时间差异无统计学意义(P>0.5),但≤0.2 ng/ml组维持PSA最低值的时间间隔(33.88个月)比>0.2 ng/ml组(16.53个月)长(P<0.05),≤0.2 ng/ml组5年累积PSA无进展存活率显著高于>0.2 ng/ml组(对数秩和检验,χ2=8.68,P<0.005),临床进展率(22%)低于>0.2 ng/ml组(50%)(χ2=5.80,P<0.025),患者总存活时间(48.4个月)高于>0.02 ng/ml组(33.1个月)(t=2.22,P<0.05).因前列腺癌死亡的患者中,≤0.2 ng/ml组平均存活时间(58.2个月)高于>0.2 ng/ml组(19.8个月)(t=6.29,P<0.001).结论:ADT后PSA最低值可能是前列腺癌患者对ADT治疗敏感程度的重要预示物,PSA最低值越低,前列腺癌的预后越好.ADT后PSA最低值未达0.2 ng/ml的患者可能处于生化和临床进展的高危状态.     

The Free-To-Total Prostate Specific Antigen Ratio Improves the Specificity of Prostate Specific Antigen in Screening for Prostate Cancer in the General Population

Purpose

The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population.

Materials and Methods

From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results.

Results

Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase in specificity compared to PSA. Retrospective application of age specific PSA reference ranges, the free-to-total PSA ratio and the PSA density decreased the number of biopsies significantly by up to 40% in our study, with a decrease in cancer detection rate of 12%. When used in combination with digital rectal examination, the pathological stage of undetected carcinomas appeared favorable.

Conclusions

The free-to-total PSA ratio may be used to decrease biopsies in patients with an intermediate PSA of 4.0 to 10.0 ng./ml.