The role of salvage surgery after failure of non-surgical first-line treatment for early stage prostate cancer

Radical prostatectomy is an option for many men who have been treated with non-surgical methods for early stage (presumed to be localized) prostate cancer, including:

  • External beam radiation therapy
  • Brachytherapy
  • Cryotherapy and
  • High-intensity focused ultrasound (HIFU)

The critical question over the years has been how good such so-called “salvage” surgery is as a clinical option for any particular man.

Until relatively recently (i.e., up until the mid-1990s), salvage surgery was carried out primarily on men who had biochemical recurrence after failure of first-line external beam radiation therapy. And few surgeons were willing to carry out salvage surgery on such patients on a regular basis, however good the surgeons were considered to be. The operation was inevitably not nerve-sparing, came with high risks for a multitude of other side effects (a high morbidity), and could leave patients with a quality of life that was unacceptably poor.

In more recent years, however, the situation has started to change. Data from two large series (published by Ward et al. and  Bianco et al.) have reported:

  • A 5-year, post-surgical probability of progression-free survival rates of 55 percent (Bianco et al.)
  • A median progression-free survival of 8.7 years (Ward et al.)
  • A 10-year, post-surgical probability of cancer-specific survival of 77 percent (Ward et al.)
  • 10- and 15-year post-surgical probabilities of prostate-cancer specific death of 27 and 40 percent (Bianco et al.) 
  • Significant improvements in complication rates and quality of life outcomes compared to historic data
  • Better local and distant cancer control

What has changed?

Well in the first place, patients today are being selected for salvage surgery based on a rising PSA after their prior therapy, as compared to the historic situation, when men receiving salvage surgery could only be selected based on actual symptoms of disease recurrence.

In the second place, there is little doubt that (as with any surgical technique), surgeons who can carefully select appropriate patients for this procedure and who practice the procedure regularly will carry out the operation with greater skill than those who do it rarely and in patients who may be less appropriate. The modern availability of magnetic resonance imaging makes it a great deal easier for the surgeon to be able to evaluate the potential for a successful procedure before he or she commits to the operation.

In a presentation given by Sokoloff et al. at the annual meeting of the American Urological Association in Orlando in 2008, the authors reported the results of CALGB 9687 — a prospective study designed to evaluate the  efficacy and morbidity of salvage radical prostatectomy (SRP) in a contemporary multi-institutional series.

The study enrolled 41 eligible patients with biopsy-proven, recurrent prostate cancer after receivingradiotherapy at a total dose level of  > 60 cGy as primary treatment for cT1-2NxM0 prostate cancer. Men were required to have pre-RT PSA level of  < 30 ng/ml and a Gleason score < 7.  Additional eligibility requirements for second-line SRP included a positive biopsy, no metastases, PSA < 20 ng/ml, >18 months since RT, and > 3 months since hormonal therapy. Pathological findings, surgical morbidity, quality of life, and disease-free and overall survival were evaluated.

Results reported by the authors were as follows:

  • 24 patients had external beam radiation therapy; 11 had brachytherapy; and 6 had both.
  • Median time to post-RT PSA nadir was 30 months, and the median time between RT and SRP was 63.6 months.
  • The median age at time of SRP was 63.9 years and median PSA was 4.1 ng/ml.
  • Median operative time was 251 minutes.
  • Pathologic staging showed that 44 percent of patients were pT2, 53.7 percent were pT3, 2.5 percent were pT4, and 17 percent had a positive surgical margin.
  • All men underwent pelvic lymphadenopathy and 88% were pN0.
  • 10 men (24 percent) required blood transfusion.
  • 17 men (45 percent) had significant incontinence (> 3 pads/day) prior to SRP
  • 13 men (32 percent) had impotence prior to SRP
  • Three rectal injuried (7%) and 1 obturator nerve (2%) injury occurred during surgery.
  • There were a number of significant adverse events post-surgery
    • 4 men (10%) had anastomotic urinary leaks
    • 12 men  (29 percent had bladder neck contractures
  • Among all 41 patients, the “time to first incontinence-free rates” at 3, 6, and 12 months post-SRP were 90, 18, and 9 percent respectively.
  • Also among all 41 patients, the “time to first erectile dysfunction-free rates” at 3, 6, and 12 months post-SRP were 87, 25, and 14 percent, respectively.
  • The 5-year biochemical progression-free survival rate was 55 percent.
  • The 5-year overall survival rate was 85 percent.

The investigators concluded that SRP is an effective treatment modality for recurrent prostate cancer after RT. In their opinions, modern surgical techniques offer complication rates that include moderate increases in baseline incontinence and impotence at 1 year after SRP. They note the fact that > 50 percent of the patients had locally advanced disease and that 12 percent had regional lymph node metastases suggest that men who fail RT for prostate cancer should be very carefully selected carefully for SRP.

However, radical prostatectomy as second-line treatment of men in biochemical failure after first-line external beam radiation is still a high-risk procedure. The greatest risk is that it may have to be converted to a radical cystoprostatectomy (removal of the prostate and the bladder). This procedure is necessary in as many as 20 percent of patients who decide on salvage surgery, and, in addition to the additional trauma, it is associated with less good long-term outcomes. And then all the other side effects of radical prostatectomy are still possible, most notably long-term incontinence and impotence of some degree.

You should also not get the idea that there are large numbers of surgeons capable of and willing to attempt salvage surgery. There are few who do it often and very few who do it often enough to claim significant clinical experience. If you want or need to consider this option, you absolutely need to go to one of those very small number of surgeons with experience!

One final word of guidance. Even in the series of Ward et al. and Bianco et al., there was often a significant delay in time between biochemical failure after first-line therapy and treatment by salvage surgery. It seems likely that, if salvage surgery were carried out quickly after biochemical failure of the first-line therapy, there is still potential for significant improvements in the surgical outcome.

We are aware of far less information about the use of salvage surgery after the failure of brachytherapy, cryotherapy, and HIFU than after the failure of exteral beam radiation therapy, and we suspect that there are few significant series of patients as yet. However, the technique is certainly possible and has certainly been carried out. There are several good reasons, in fact, for believing that salvage surgery after these techniques may be less complicated than following external beam radiation, but this is still not as simple a procedure as a radical prostatectomy of an otherwise untreated prostate gland.

Most recently we saw the first publication of a series of patients who had been treated with laparoscopic salvage radical prostatectomy. This report came from a German team with extensive experience in the use of LRP, but we can reasonably expect teams in other countries to replicate this work in the near future (if they aren’t already). Liatsikos et al. reported salvage LRPs on 12 men, including patients whose first-line treatments had been brachytherapy, HIFU, and external beam radiation. All patients had been treated by a single surgeon. The authors reported that, “salvage [LRP] in experienced hands has minimal perioperative morbidity. Short term oncological and functional outcomes are encouraging but further studies and longer follow-up are required in order to assess the long-term outcomes.”

Murphy et al. reported the first case of the use of salvage robot-assisted laparoscopic prostatectomy (RALP) in a man who had biochemical failure after treatment with HIFU. Similarly, Jamal et al. have reported the use of salvage RALP in a man who had biochemical failure following external beam radiation. We can expect the number of men receiving salvage RALPs to increase rapidly.

Content on this page last reviewed and updated December 30, 2008.
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