Edith Canby-Hagino

Adjuvant Radiotherapy for Pathological T3N0M0 Prostate Cancer Significantly Reduces Risk of Metastases and Improves Survival: Long-Term Followup of a Randomized Clinical Trial

PURPOSE Extraprostatic disease will be manifest in a third of men after radical prostatectomy. We present the long-term followup of a randomized clinical trial of radiotherapy to reduce the risk of subsequent metastatic disease and death. MATERIALS AND METHODS A total of 431 men with pT3N0M0 prostate cancer were randomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primary study end point was metastasis-free survival. RESULTS Of 425 eligible men 211 were randomized to observation and 214 to adjuvant radiation. Of those men under observation 70 ultimately received radiotherapy. Metastasis-free survival was significantly greater with radiotherapy (93 of 214 events on the radiotherapy arm vs 114 of 211 events on observation; HR 0.71; 95% CI 0.54, 0.94; p = 0.016). Survival improved significantly with adjuvant radiation (88 deaths of 214 on the radiotherapy arm vs 110 deaths of 211 on observation; HR 0.72; 95% CI 0.55, 0.96; p = 0.023). CONCLUSIONS Adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival.

Predominant Treatment Failure in Postprostatectomy Patients Is Local: Analysis of Patterns of Treatment Failure in SWOG 8794

PURPOSE Southwest Oncology Group (SWOG) trial 8794 demonstrated that adjuvant radiation reduces the risk of biochemical (prostate-specific antigen [PSA]) treatment failure by 50% over radical prostatectomy alone. In this analysis, we stratified patients as to their preradiation PSA levels and correlated it with outcomes such as PSA treatment failure, local recurrence, and distant failure, to serve as guidelines for future research. PATIENTS AND METHODS Four hundred thirty-one subjects with pathologically advanced prostate cancer (extraprostatic extension, positive surgical margins, or seminal vesicle invasion) were randomly assigned to adjuvant radiotherapy or observation. RESULTS Three hundred seventy-four eligible patients had immediate postprostatectomy and follow-up PSA data. Median follow-up was 10.2 years. For patients with a postsurgical PSA of 0.2 ng/mL, radiation was associated with reductions in the 10-year risk of biochemical treatment failure (72% to 42%), local failures (20% to 7%), and distant failures (12% to 4%). For patients with a postsurgical PSA between higher than 0.2 and <or = 1.0 ng/mL, reductions in the 10-year risk of biochemical failure (80% to 73%), local failures (25% to 9%), and distant failures (16% to 12%) were realized. In patients with postsurgical PSA higher than 1.0, the respective findings were 94% versus 100%, 28% versus 9%, and 44% versus 18%. CONCLUSION The pattern of treatment failure in high-risk patients is predominantly local with a surprisingly low incidence of metastatic failure. Adjuvant radiation to the prostate bed reduces the risk of metastatic disease and biochemical failure at all postsurgical PSA levels. Further improvement in reducing local treatment failure is likely to have the greatest impact on outcome in high-risk patients after prostatectomy.

Single dose levofloxacin prophylaxis for prostate biopsy in patients at low risk

PURPOSE We determine if a single 500 mg. oral tablet of levofloxacin represents adequate prophylaxis for patients at low risk who undergo transrectal prostate biopsy. MATERIALS AND METHODS From April 2000 to May 2001 we prospectively evaluated 400 consecutive men who underwent transrectal needle biopsy of the prostate after a single 500 mg. oral dose of levofloxacin. Under an institutional review board approved protocol the drug was issued under a standing order by a clinic nurse 30 to 60 minutes before the procedure. Patients were issued 2 additional daily doses of levofloxacin if they were deemed at increased risk for infectious complications, that is if they had a large prostate more than 75 cc, diabetes mellitus, recent steroid use, severe voiding dysfunction or immune compromise. No patient received a cleansing enema before the procedure. Complications, the number of biopsy cores, prostate size and cancer detection rates were assessed. RESULTS Only 1 of the 377 patients at low risk in whom biopsy was completed experienced a symptomatic urinary tract infection (0.27%). None of the 23 men at high risk who received additional doses of levofloxacin experienced a complication. Thus, the overall infection rate was 1 of 400 cases (0.25%) in this series. A mean of 7 biopsy cores (range 2 to 16) was obtained per patient and mean prostate volume was 49.75 cc (range 12 to 150). Prostate cancer was present in 93 patients (23%). CONCLUSIONS A single 500 mg. dose of levofloxacin before transrectal needle biopsy of the prostate is effective and safe in patients at low risk. The administration of prophylaxis by a clinic nurse under a standing order optimizes patient compliance and physician efficiency. In patients at higher risk for infection additional antibiotic administration appears to provide adequate prophylaxis.

FIBRIN SEALANT TREATMENT OF SPLENIC INJURY DURING OPEN AND LAPAROSCOPIC LEFT RADICAL NEPHRECTOMY

PURPOSE We describe the use of fibrin sealant for rapid and definitive hemostasis of splenic injuries incurred during open and laparoscopic left nephrectomy. MATERIALS AND METHODS In 2 patients undergoing left nephrectomy for a suspicious renal mass splenic laceration occurred during mobilization of the colonic splenic flexure at open nephrectomy and laparoscopic upper pole dissection, respectively. Fibrin sealant was applied topically in each case. RESULTS In each patient fibrin sealant achieved immediate hemostasis and each recovered without further splenic bleeding. CONCLUSIONS The topical application of fibrin sealant safely, rapidly and reliably achieves definitive hemostasis of splenic injuries. It is simple to use in the open and laparoscopic approaches.

The Prognostic Impact of Seminal Vesicle Involvement Found at Prostatectomy and the Effects of Adjuvant Radiation: Data From Southwest Oncology Group 8794

PURPOSE From the randomized study Southwest Oncology Group 8794 we evaluated the effect of seminal vesicle involvement on outcomes and whether those patients benefited from post-prostatectomy adjuvant radiation therapy. MATERIALS AND METHODS Southwest Oncology Group study 8794 randomized high risk patients (with seminal vesicle positive disease and/or capsular penetration and/or positive margins) to radiation vs observation after prostatectomy. A total of 431 subjects with pathologically advanced prostate cancer were randomized. RESULTS Median followup was 12.2 years. Of the patients 139 had seminal vesicle involvement with or without capsular penetration and/or positive margins. Compared to the 286 patients with seminal vesicle negative disease there was poorer 10-year biochemical failure-free survival (33% for seminal vesicle negative and 22% for seminal vesicle positive, p = 0.04), metastasis-free survival (70% and 56%, respectively, p = 0.005) and overall survival (10-year overall survival 74% and 61%, respectively, p = 0.02) for those with seminal vesicle positive disease. Patients with seminal vesicle positive disease who received adjuvant radiation compared to observation realized an improvement in 10-year biochemical failure-free survival from 12% to 36% (p = 0.001), in 10-year overall survival from 51% to 71% (p = 0.08) and in metastasis-free survival from 47% to 66% (p = 0.09), respectively. CONCLUSIONS Although seminal vesicle involvement is a negative prognostic factor, long-term control is possible especially if patients are given adjuvant radiation therapy. This therapy appears to be effective in patients with seminal vesicle involvement.

Ten-year follow-up of neoadjuvant therapy with goserelin acetate and flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: Update on southwest oncology group study 9109

OBJECTIVE To update the results with 10-year data of a phase II prospective trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy for locally advanced prostate cancer (SWOG 9109). The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer is uncertain. MATERIALS AND METHODS Sixty-two patients with clinical stage T3 and T4 N0,M0 prostate cancer were enrolled. Cases were classified by stage T3 vs T4 and by volume of disease (bulky >4 cm and nonbulky ≤ 4 cm). RESULTS Fifty-five of 61 eligible patients completed the trial with radical prostatectomy after neoadjuvant androgen deprivation therapy (ADT). The median preoperative prostate-specific antigen value was 19.8 ng/mL, and 67% of patients had a Gleason score of ≥ 7. Among 41 patients last known to be alive, median follow-up is 10.6 years (range 5.1-12.6). In all, 38 patients have had disease progression (30/55, 55%) or died without progression (8/55, 15%) for a 10-year progression-free survival (PFS) estimate of 40% (95% CI 27-53). Median PFS was 7.5 years, and median survival has not been reached. The 10-year overall survival (OS) estimate is 68% (95% CI 56-80). CONCLUSIONS In this small, prospective phase II study, neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy achieves long-term PFS and OS comparable with alternative treatments. This approach is feasible and may be an alternative to a strategy of combined radiation and ADT.

INTRALUMINAL PNEUMATIC LITHOTRIPSY FOR THE REMOVAL OF ENCRUSTED URINARY CATHETERS

PURPOSE Urologists frequently treat patients requiring long-term urinary drainage with a percutaneous nephrostomy tube or ureteral stent. When such tubes are neglected and become encrusted, removal challenges even experienced urologists. We describe a new, minimally invasive technique for safely and rapidly removing encrusted, occluded tubes using the Swiss Lithoclast pneumatic lithotriptor. MATERIALS AND METHODS Patients presenting with an encrusted urinary catheter were evaluated by excretory urography for renal function and obstruction. Gentle manual extraction of the tube was attempted, followed by traditional extracorporeal shock wave lithotripsy and/or ureteroscopy. When the tube was not extracted, patients were then treated with intraluminal insertion of a pneumatic lithotripsy probe. RESULTS One patient presented with an encrusted, occluded nephrostomy tube and 2 had an encrusted, occluded, indwelling ureteral stent. None was removed by manual traction. Intraluminal encrustations prevented the pigtail portions of these tubes from uncoiling and removal. In each case a pneumatic lithotripsy probe was inserted into the lumen of the catheter and advanced in a jackhammer-like fashion. This technique resulted in disruption of the intraluminal encrustations and straightening of the tubes so that they were removed in an atraumatic manner. CONCLUSIONS Intraluminal pneumatic lithotripsy is a safe, easy and rapid technique for removing encrusted urinary catheters. It is unique in that the pneumatic lithotripsy probe functions in an aqueous and nonaqueous environment, and dislodges intraluminal calcifications. We recommend its use as first line treatment for removing encrusted urinary catheters.

Local and systemic therapy for patients with metastatic prostate cancer: Should the primary tumor be treated?

Data from well-designed, prospective clinical trials are lacking to support treatment of primary tumor in men diagnosed with metastatic prostate cancer. However, a growing body of evidence suggests that treatment of the primary tumor may enhance cancer control and survival in some men. This evidence is examined and recommendations are made for identifying patients with metastatic prostate cancer who may benefit from definitive treatment of the prostate tumor.

Chemoprevention of prostate cancer with finasteride

Prostate cancer is a significant cause of disease and death, making it an attractive target for chemoprevention. The association between lifetime exposure to dihydrotestosterone and risk of developing prostate cancer suggests that chemoprevention is possible with 5α-reductase inhibition. The recently completed Prostate Cancer Prevention Trial indicates that chemoprevention is possible with the 5α-reductase inhibitor finasteride. Development of a cost-effective chemoprevention strategy for prostate cancer is evolving, and is expected to have significant positive economic and public health benefits.

Prostate cancer detection strategies

Prostate cancer is the most common malignancy in men and, as a result, there has been a nationwide emphasis on screening and detection. With the widespread use of the prostate-specific antigen (PSA), prostate cancer screening effectively detects localized prostate cancer. However, recent reports have identified a significant proportion of prostate cancer in men with low PSA levels. Many of these cancers are higher-grade malignancies. Consequently, PSA may function more effectively as a screening tool when applied over a continuum that is associated with degree of risk, rather than a binary measure. Other markers are currently being investigated. Ideally, a marker will identify the malignancy that is a clinical threat, thereby avoiding intervention for indolent disease. Prevention strategies may be employed for higher-risk patients, and these strategies eventually may be tailored to genetic or other risks.