Multimodal therapy extends survival in node-positive prostate cancer

November 1, 2008

Lymph node-positive prostate cancer is not always indicative of systemic disease.

The not-so-small challenge now is to determine which patients will achieve the greatest benefit from which combinations of treatment, first author Alberto Briganti, MD, a urologist at University Vita-Salute, Hospital San Raffaele, Milan, Italy, told Urology Times. Data from this study were presented at the AUA annual meeting in Orlando, FL.

The study found that more than 50% of men treated with surgery, extended pelvic lymph node dissection, and adjuvant therapy (radiotherapy, hormonal therapy, or both) were disease free at 10 years follow-up.

Many collaborators in the study were involved in a second study that developed an internally validated nomogram for assessing long-term, disease-specific survival in patients with node-positive cancer treated with radical prostatectomy and pelvic lymph node dissection. This nomogram, the first for node-positive patients, predicts survival with close to 73% accuracy, according to study findings.

The collaborative team from Italy, Germany, and Canada identified 285 patients treated with radical prostatectomy and adjuvant therapy between 1988 and 2003. Of these, 144 patients (50.5%) were treated with radiotherapy and hormonal therapy while the remaining 141 (49.4%) received only adjuvant hormonal therapy.

The mean number of nodes removed was 16.7; of these, the mean number of positive nodes found was 2.7. Mean follow-up was 90 months, with biochemical recurrence-free (BCR) survival rates at 5, 8, and 10 years being 72%, 61%, and 53%, respectively.

In a Cox regression analysis, pre-operative PSA, number of positive nodes removed, and adjuvant radiotherapy held a significant association with BCR survival, while the number of nodes removed, pathologic stage, and pathologic Gleason score were not independent predictors of BCR survival.

"Dissection included removal of the obturator, external iliac, and hypogastric nodes. We had a mean of 17 nodes removed per patient. This is a key point. The number of nodes removed, despite what some may think, is never associated with outcomes; however, the number of positive nodes is important," Dr. Briganti told Urology Times.

The second study presented by Dr. Briganti looked at 696 patients with lymph node metastases treated with radical prostatectomy and pelvic lymph node dissection treated at two large academic institutions. All patients received some form of adjuvant therapy. Of these, 526 patients (75.6%) received only hormonal therapy while 170 (24.4%) received adjuvant hormonal therapy combined with radiotherapy.

Univariable and multivariable Cox regression analyses considered the association between preoperative PSA, pathologic stage, Gleason score, number of positive nodes, surgical margin status, and adjuvant radiotherapy.

This study found that the number of positive nodes, pathologic Gleason score, surgical margin status, and adjuvant radiotherapy were significant predictors of cancer-specific survival. The nomogram subsequently developed around these factors has an internally validated accuracy of 72.7% in predicting disease-specific survival in node-positive patients who were treated with a multimodal approach.

"It is clear that node-positive patients have a wide range of outcomes," Dr. Briganti said. "Some will die of the disease, and some will not.

"We have to be able to stratify patients according to the risk of recurrence or cancer-specific death: those patients who can just be observed and those in whom we need to be aggressive. Some of these patients may be spared adjuvant hormonal treatment, which has significant side effects."