Emma Hitt, PhD

Neoadjuvant docetaxel added to androgen suppression therapy and radiation therapy appears to be safe and active in patients with high-risk localized prostate cancer, according to findings of a new phase II study from Canada reported here at the American Society of Clinical Oncology annual meeting. 

The current study, a seven-center trial led by Michael R. McKenzie, MD, a radiation oncologist at the British Columbia Cancer Agency, Vancouver Cancer Centre, sought to assess the tolerability of neoadjuvant docetaxel with androgen suppression therapy and radiation therapy in men with high-risk localized prostate cancer. 

All of the men received 3 years of androgen suppression therapy consisting of an LHRH agonist plus an anti-androgen for 4 weeks followed by chemotherapy starting at week 5. Twenty-four men received weekly docetaxel, 35 mg/m

  for 6 weeks, given every 8 weeks for two cycles. Radiation therapy was started at week 25. 

After a revision of the protocol, 30 men received docetaxel, 75 mg/m

  every 3 weeks for 4 cycles, followed by radiation therapy starting at week 21.  

				The primary endpoint was unacceptable toxicity, defined as greater than grade 3 nonhematologic toxicity, grade 4 neutropenia lasting beyond 7 days, febrile neutropenia, or toxicity-related radiation therapy change (a delay greater than 2 weeks or a dose reduction of 25%).			

An analysis of the data after all men had completed radiation therapy indicated that neoadjuvant androgen suppression therapy and docetaxel in combination with radiation therapy was generally well tolerated. 

Of the 54 men, eight (14.8%) were classified as having unacceptable toxicity. Among these were five patients who were receiving once-weekly docetaxel: three developed grade 3 acute radiation therapy-related genitourinary toxicity, one had grade 3 docetaxel hypersensitivity, and one had grade 3 fatigue for more than 2 weeks. 

				In three patients receiving docetaxel every 3 weeks, unacceptable toxicities included grade 3 acute radiation therapy-related genitourinary toxicity (one patient), febrile neutropenia (one patient), and grade 4 neutropenia for more than 7 days (one patient).			

Approximately one-third of the men (35.2%) achieved PSA levels between 0.1 and 0.5 μg/L in response to neoadjuvant treatment; 23 patients (42.6%) achieved PSA levels between 0.5 μg/L and 2.0 μg/L; and three (5.6%) patients had PSA levels >2.0 μg/L.  

The combination of radiation therapy and hormone therapy is better than radiation therapy alone, but a significant proportion of patients still relapse on therapy, according to Dr. McKenzie. 

"Given the results of docetaxel in hormone-refractory and hormone-sensitive disease, it seemed logical to explore the potential benefits of docetaxel in this setting," he told 

				He added that the researchers were concerned about whether the combination would be tolerable in a relatively older population of men, and "we were able to show that it was."			

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Atlanta-Neoadjuvant docetaxel added to androgen suppression therapy and radiation therapy appears to be safe and active in patients with high-risk localized prostate cancer, according to findings of a new phase II study from Canada reported here at the American Society of Clinical Oncology annual meeting.

Neoadjuvant chemo is well tolerated in high-risk PCa

Positive surgical margin rates decrease as experience with robot-assisted laparoscopic prostatectomy (RALP) increases. In addition, formal laparoscopic training may not be necessary for optimizing some outcomes with the robotic procedure, according to the findings of two new studies presented here at the AUA annual meeting. 

Surgical specimens from 366 patients were evaluated. Specimens were immersed in ink and assessed by histologic evaluation of 5-mm incremental step sections. A positive margin was defined as the presence of any tumor cells that reached the inked margin or that were located at the site of a capsular incision, even if a negative margin was observed on subsequent excision. 

"Achieving expertise with RALP re-quires acquisition of a different skill set for surgeons primarily acquainted with open surgical approaches," Dr. Herrell and his colleagues wrote. 

They also suggested that early outcomes with RALP produced more positive margins than radical retropubic prostatectomy does, although this was not statistically significant. However, after the initial patient groups, positive margin rates for the robot-assisted procedure were lower than were those for the traditional retropubic procedure. 

 that measures of other outcomes, such as sexual function and continence, are still pending. 

"We have not seen an advantage with RALP outcomes in terms of length of stay or reduction in pain, although we have seen a slight advantage in terms of blood loss," he said. 

A second study, presented by David P. Wood, Jr, MD, professor of urology at the University of Michigan, Ann Arbor, sought to determine the importance of laparoscopy and oncology training in outcomes with RALP using the daVinci robot. 

Dr. Wood and colleagues evaluated the initial experience of three urologists with the robotic procedure. One was a fellowship-trained oncologist with limited laparoscopic experience; another was fellowship-trained in minimally invasive urology, but had limited experience with radical retropubic prostatectomy since residency; and the third urologist had combined fellowship training in oncology and minimally invasive surgery. 

Pathologic, intraoperative, and postoperative outcomes from each surgeon's first 10 RALP procedures were compared. Patient characteristics were similar among the three surgeons' cases. 

 The fellowship-trained laparoscopist had a higher median operative time and more blood loss than did both the surgeon with combined training and the oncology-trained urologist for the 10 cases. Operative times were 389 minutes, 266 minutes, and 248 minutes for the laparoscopist, oncologist, and combined-training surgeon, respectively (

<.001); blood loss was 375 mL, 132 mL, and 175 mL, respectively (

=.004). Average length of patient hospital stay was 2 days for the laparoscopist compared with 1 day for each of the other two surgeons. 

Conversion to open prostatectomy, positive surgical margins (focal)/extraprostatic extension, and urine leak/bladder neck contracture were comparable among the three surgeons. 

"These findings indicate that surgeons who are comfortable performing an open prostatectomy will learn robotic prostatectomy relatively quickly, even if they have rudimentary laparoscopic skills," Dr. Wood told 

Atlanta-Positive surgical margin rates decrease as experience with robot-assisted laparoscopic prostatectomy (RALP) increases. In addition, formal laparoscopic training may not be necessary for optimizing some outcomes with the robotic procedure, according to the findings of two new studies presented here at the AUA annual meeting.

RALP may offer improved margins, ease of transition

Men with smaller prostate glands appear to be more likely to develop prostate cancer and have higher Gleason sum disease than are men with larger prostates, according to the results of a new prospective analysis. 

"We have previously published findings regarding a relationship between prostate cancer diagnosis (ie, positive transrectal ultrasound) and low AUA symptom score 

. "In this analysis, we wanted to evaluate the relationship of Gleason sum to gland volume more closely." 

Median and mean PSA levels of the patients were 5.4 ng/mL and 10.4 ng/mL, respectively. Thirty-eight percent had an abnormal TRUS, and 52% had an abnormal DRE. The mean AUA symptom score was 10.4, with 47% of the men having a score of <7 (mild) and 14% having scores of 20 to 35 (severe). The positive biopsy rate was 38%. 

 Multivariate analysis of 790 patients who had not undergone prior biopsy indicated that low prostate volume, high PSA levels, positive DRE, and advanced age were independent predictors for prostate cancer (

<.0001). In addition, multivariate analysis found that Gleason sum ≥7 on biopsy was independently associated with both abnormal DRE and low prostate volume (

=.001 for both), and that for every cubic centimeter increase in gland volume, the risk of prostate cancer with Gleason sum ≥7 decreased by 2.2%. 

According to Dr. Porter, these results may be explained by the fact that men are more likely to see their urologist and to be screened for prostate cancer if they are experiencing voiding symptoms. 

"Therefore, men with smaller glands may be postulated to be less likely to see their urologist and to undergo screening," he said. "It is entirely possible that we are missing a large body of men in the population who may be more likely to have prostate cancer, primarily because they are less likely to be seen by their urologist." 

The biologic rationale for men with smaller prostates having increased likelihood of cancer and significant disease has been illustrated in findings from the Prostate Cancer Prevention Trial, in which it was demonstrated that men with smaller glands were more likely to have higher-grade prostate cancer (

Another hypothesis may involve the relationship between BPH and prostate cancer, Dr. Porter said. 

"It is possible that BPH exerts a protective effect on the prostate cells, and that benign cellular growth, either through substrate use or through the release of an unknown factor, may protect the cell from molecular changes that could spurn malignant change," he said. 

Atlanta-Men with smaller prostate glands appear to be more likely to develop prostate cancer and have higher Gleason sum disease than are men with larger prostates, according to the results of a new prospective analysis.

Smaller prostate gland associated with high-grade PCa

-Radical retropubic prostatectomy and external beam radiation therapy (XRT) show no significant difference in efficacy outcomes in men with clinically localized prostate cancer, according to findings from an interim phase III analysis from Italy. In terms of health-related quality of life, XRT offers a slight edge on some, but not all, measures, researchers reported at the American Society of Clinical Oncology annual meeting here. 

Patients were recruited between January 1997 and September 2001, and 137 patients were randomized to undergo either retropubic RP or XRT. They were followed for a median of 67 months. Data were analyzed on an intent-to-treat basis. 

No significant differences in clinical disease progression and survival rates were observed between surgery and radiation therapy, reported first author Savino Mauro Di Stasi, MD, PhD, associate professor of urology of Tor Vergata University in Rome. At median follow-up, 32.8% of the patients had evidence of biochemical disease progression: 32.8% in the XRT group and 31.4% in the prostatectomy group. The median time to biochemical failure was 55.5 months among patients undergoing surgery versus 56 months for those receiving XRT. 

Prostate cancer-related deaths were observed in 4.3% and 1.5% of the surgery and radiation therapy patients, respectively. 

 Before treatment and after 1, 3, 6, 12, and 24 months, 47 patients in the prostatectomy group and 49 in the XRT group completed a questionnaire assessing their general health-related quality of life (Functional Assessment of Cancer Therapy-General [FACT-G]) and specific changes in urinary, bowel, and sexual functions (UCLA Prostate Cancer Index [UCLA-PCI]).  

"A larger sample size accrual and long-term follow-up data are warranted to confirm these results," the researchers noted.  

"These represent interim findings, and it is difficult to make a definitive statement about the efficacy of treatment," Dr. Di Stasi told 

. "However, there were obvious differences in quality of life in the treatment groups, and these findings can help serve as a discussion point for patients deciding upon a treatment." 

Surgery has greater impact on urinary function;......radiation therapy, on bowel function

Emma Hitt, PhD

Articles

Neoadjuvant chemo is well tolerated in high-risk PCa

RALP may offer improved margins, ease of transition

Smaller prostate gland associated with high-grade PCa

RRP vs. XRT: Similar outcomes, some quality of life differences