A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer.

BACKGROUND: Localized prostate cancer can be treated several different ways, but head-to-head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate-specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir + 2 ng/mL. Secondary endpoints included overall survival, disease-specific survival, and prostate biopsy at 36 months. RESULTS: The median follow-up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir + 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir + 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease-specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer-positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%). CONCLUSIONS: The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from -10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow-up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy.

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer: quality of life outcomes.

BACKGROUND: A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease-specific survival. We report on the quality of life (QOL) outcomes for this trial. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were randomly assigned to cryoablation or EBRT (median dose 68 Gy). All patients received neoadjuvant antiandrogen therapy. Patients completed the EORTC QLQ C30 and the Prostate Cancer Index (PCI) before treatment and at 1.5, 3, 6, 12, 18, 24, and 36 months post-treatment. RESULTS: Regardless of treatment arm, participants reported high levels of QOL with few exceptions. cryoablation was associated with more acute urinary dysfunction (mean PCI urinary function cryoablation=69.4; mean EBRT=90.7; P<.001), which resolved over time. No late arising QOL issues were observed. Both EBRT and cryoablation participants reported decreases in sexual function at 3 months with the cryoablation patients reporting poorer functioning (mean cryoablation=7.2: mean EBRT=32.9; P<.001). Mean sexual function score was 15 points lower at 3 years for the cryoablation group and 13% more of the cryoablation men said that sexuality was a moderate or big problem. CONCLUSIONS: In this randomized trial, no long-term QOL advantage for either treatment was apparent with the exception of poorer sexual function reported by those treated with cryoablation. Men who wish to increase their odds of retaining sexual function might be counseled to choose EBRT over cryoablation.

A near-fatal case of sepsis with an antibiotic-resistant organism complicating a routine transrectal prostate biopsy in a health care worker.

A 58-year-old physician with an elevated prostate specific antigen developed severe septic shock following a repeat transrectal prostate biopsy despite standard preoperative prophylactic protocol. This case highlights the significance of harbouring antibiotic-resistant bacteria and the risk of previous quinolone exposure. We believe this case may herald a rare but potentially serious consequence of increasingly common antibiotic resistance and that high-risk patients should be studied to determine their likelihood of carrying antibiotic-resistant flora in their genitourinary/gastrointestinal tract.

Quality of life 2 years after salvage cryosurgery for the treatment of local recurrence of prostate cancer after radiotherapy.

PURPOSE: Previous research has raised concerns that although salvage cryosurgery may be an effective treatment to prevent the progression of prostate cancer after radiotherapy failure, the quality of life cost many be so severe as to prevent its acceptance as a viable treatment. The present study's purpose was to further the understanding of the quality of life outcomes of salvage cryosurgery. MATERIALS AND METHODS: A total of 46 men with locally recurrent prostate cancer after radiotherapy were recruited to participate in a prospective Phase II clinical trial using salvage cryosurgery. There were 2 questionnaires (i.e., the European Organization of Research and Treatment of Cancer QLQ C30 and the Prostate Cancer Index) administered before cryosurgery, and at 1.5, 3, 6, 12, 18, and 24 months after treatment. RESULTS: Quality of life returned to preoperative levels by 24 months after cryosurgery in all domains, with the exception of urinary and sexual functioning. At 24 months, 29% of men reported urinary bother as a moderate-to-big problem, and 56% reported sexual bother as a moderate-to-big problem. CONCLUSIONS: To our knowledge, this is the first study to evaluate prospectively men's quality of life for 2 years after salvage cryosurgery for locally recurrent prostate cancer after radiotherapy. Long-term impairments in quality of life appear to be limited to the sexual and urinary function domains. Overall quality of life appears to be high. These results support salvage cryosurgery as a viable treatment option.

Prostate cancer: gadolinium-enhanced MR imaging at 3 weeks compared with needle biopsy at 6 months after cryoablation.

PURPOSE: To determine if nonenhancing tissue on gadolinium-enhanced magnetic resonance (MR) images obtained 3 weeks after cryoablation of the prostate helps reliably and accurately predict nonviable cryoablated tissue at 6-month biopsy. MATERIALS AND METHODS: Fifty-four consecutive patients with prostate cancer who underwent cryoablation were followed up prospectively. Fifty-one underwent gadolinium-enhanced MR imaging at 3 weeks (three had gadolinium allergy); 49, biopsy at 6 months (three refused and two had other primary malignancies); and all, prostate-specific antigen (PSA) tests at 6 weeks, 3 months, and every 3 months thereafter. MR images were evaluated and scored according to the degree of signal void and were correlated with the 6-month biopsy reports and, to a lesser degree, PSA levels. The biopsy reports were examined for the presence or absence of cancerous tissue, viable tissue, and nonviable tissue. A one-way analysis of variance was used for statistical and regression analyses. RESULTS: The correlation of MR imaging scores with PSA levels and MR imaging scores with biopsy findings resulted in P values of.337 and.780, respectively. A slight statistically significant trend existed for the relation of biopsy results with PSA levels, with a P value of.041, which was expected. CONCLUSION: Findings of postoperative gadolinium-enhanced MR imaging are not predictive of 6-month biopsy results or follow-up PSA levels.

Quality of life and sexuality of men with prostate cancer 3 years after cryosurgery.

The current study was designed to describe the long-term life quality and sexuality of men enrolled in a phase 2 clinical trial of cryosurgery for the treatment of localized prostate cancer. A total of 75 men were administered the Functional Assessment of Cancer Treatment-Prostate (FACT-P) before treatment and after treatment at 6 weeks, and at 3, 6, 12, 24, and 36 months. Additionally, these men completed a Sexuality Follow-Up Questionnaire (SFQ) 3 years after cryosurgery. By 12 months after cryosurgery, most FACT-P subscales had returned to pretreatment levels. Quality of life remained stable over the subsequent 2 years. The only exception to this general trend was persistent impairment in measures of social/family well-being. At 36 months, 13% (5 of 38) of patients had regained erectile functioning, and an additional 34% (13 of 38) of patients were sexually active with the help of aids. The 3-year quality-of-life outcomes support the renewed interest in cryosurgery. No late complications were observed. Whereas improvements in erectile function were observed between years 1 and 3 for some patients, most continue to experience erectile dysfunction. For these patients, aids are an important adjunct to the treatment of their erectile dysfunction.

The evolution and state of modern technology for prostate cryosurgery.

Cryosurgery is the in situ ablation of a target tissue by application of extreme cold temperature. The ability of cryosurgery to ablate tissue is unquestioned. It is the controlled application of a cryoinjury in a manner to minimize morbidity that is problematic. Prostate cryosurgery is complicated by the proximity of the prostate to adjacent structures that are sensitive to a freeze injury, namely the urethra, rectal wall, and neurovascular bundles. Several recent technological advances have led to the development of an effective treatment protocol with acceptable morbidity. These include the advent of real-time transrectal ultrasound, cryomachines with almost instant freeze-thaw control through the use of the Joule-Thompson effect, and warming catheters to effectively preserve the integrity of the urethra and external sphincter. Further, temperature monitoring at the posterior margin of the prostate sometimes combined with an injection of saline solution into Denonvilliers fascia has reduced the occurrence of urethrorectal fistula formation to 0% to 0.5% in modern series. We review the key innovations of prostate cryosurgery that differentiate this state-of-the-art procedure from that used by early investigators to even that of the early 1990s. Potential future innovations, specifically related to image guidance of the procedure, are also addressed.

Salvage cryosurgery-how I do it.

Prostate cryosurgery has advanced over the last decade, and is now recognized as a treatment option for patients who have failed radiotherapy. Appropriate patient selection is imperative for successful salvage. Because the treatment is a local therapy, the recurrent cancer must be confined to the prostate and its immediate area, and up to half of patients who undergo salvage cryotherapy may eventually fail treatment because of occult synchronous metastases. Yet some patients with poor prognosticators may still benefit from salvage treatment.

Pilot study to determine safety and short-term outcome of percutaneous cryoablation in the treatment of localized prostate cancer (stages T1C-T3C NO MO).

OBJECTIVE: To assess the effectiveness of cryoablation in localized prostate cancer in our hands. Early end points are biopsy at 5 months and PSA at 12 months follow-up. METHODS: Percutaneous transperineal cryoablation was performed on 30 patients. A urethral warming catheter was used. All cases were newly diagnosed with no prior radiotherapy, or neoadjuvant hormones. A single freeze cycle was used in the first 10 cases and two cycles in the next 20 cases. RESULTS: Twenty-nine of 30 cases are eligible for follow-up. Six of the first 10 patients had negative biopsies, the 4 positive patients have had repeat cryoablation and only 1 patient remains biopsy positive. In cases 11-30, there were two patients with positive biopsies ­ both retreated. At this time, 27/29 patients (93%) have a negative biopsy after one (23 patients) or two (6 patients) treatments. At 6 months, 20/29 patients (69%) have undetectable PSA; 25/29 have PSA less than 1 ng/ml. At 12 months, 17/23 cases have an undetectable PSA (74%). Complications were minimal; 3 cases (10%) suffered urethral sloughing requiring TURP. CONCLUSION: Early results are very encouraging, showing 93% negative biopsy rate after one (23 patients) or two (6 patients) treatments; PSA is undetectable in 74% (17/23 patients) at 1 year. Early results of cryoablation for prostate cancer are encouraging.