After Local Treatments
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Introduction

Local treatments are intended to eliminate cancer in (and sometimes around) the prostate. Recurrence may be due to cancer remaining in the prostate bed and/or tumors that are remote from that area.

Evaluating Options

For recurrence after local treatments, your decisions include:

  • If your cancer is believed to be confined to the prostate bed, you can consider another local treatment to try again for a chance of a “cure”. You should weigh this possibility against the risk of additional side-effects. See the discussions below for options after each local treatment.
  • If your cancer location is uncertain but it appears to be slow growing, you can consider active surveillance and delay treatment until clinical progression is verified.
  • If your cancer location is unknown and there is evidence of aggressive progression or there is evidence of metastases, a variety of systemic treatments can be considered.
  • In all cases, you may want to investigate a CLINICAL TRIAL to potentially benefit from new developments and help advance the research for prostate cancer.

See: Salvage Options for Rising PSA After Primary Therapy PDF

Should androgen deprivation be your next option?

Medical experts continue to debate the advisability of starting androgen deprivation (ADT) immediately in men with PSA-only relapse. The debate is likely to continue because there are no prospective trials. The retrospective trials are less authoritative. The situation is also complicated by differences between patients — some men have relapses that are very slow-paced whereas others have a type of disease that progresses rapidly. And many studies confuse matters by inappropriately jumbling both groups together, making outcomes difficult to interpret.

Despite all these conflicting reports, several studies confirm that there is a benefit for starting ADT before the onset of bone metastasis. This is seen most clearly in studies done in men with faster PSA-doubling time (PSADT < 6 months). Recommendations vary when it comes to selecting a predetermined PSA threshold to begin treatment. Numbers like 5, 10 or 20 are suggested as the trigger for starting ADT but other factors, including Gleason score and PSA doubling time, also need to be taken into account. PSA alone fails to portray the whole picture.

For a discussion of this topic with references, see:

The following is edited from an abstract presented by Trock, et al. at the 2009 AUA Conference[1],  “in a multivariable model adjusting for PSADT, pathologic stage, Gleason score from prostatectomy (RP), time from RP to biochemical failure, and year of RP; salvage ADT strongly improved overall survival in men with PSADT <6 months. In contrast, salvage ADT did not improve overall survival in men with PSADT >6 months.

In a discussion of PSA relapse after external-beam radiotherapy, Zelefsky et al. concluded: “Patients who develop biochemical relapse with PSA-Doubling Time of less than 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid distance metastasis development.”[2]

 

Should salvage local treatment be your next option?

After Radical Prostatectomy

The PSA level should become undetectable within 6 weeks of radical prostatectomy (RP), as the prostate tissue has been removed, and the half-life of PSA is around 3 days.[3] A minimally detectable PSA that remains stable is not uncommon if a small amount of normal prostate gland tissue is left at the bladder neck or along the nerve bundles.

Radical prostatectomy failure can be defined as a PSA > 0.2 or by a detectable and rising PSA value. We suggest patients monitor PSA after RP with an ultrasensitive assay to identify failure earlier.

For some patients, radiation to the prostate bed and pelvic region may provide a second opportunity for “cure”. This must be balanced against the risk of additional side-effects.

In general, salvage radiation is a better option for men with: very low PSA; positive surgical margins; positive seminal vesicles and/or extracapsular extension. Men with higher PSA or Gleason score should consider additional imaging to see if metastatic cancer is apparent before deciding on salvage radiation.

Key considerations:

  • Calculate the PSA Doubling Time (PSADT) using exact PSA dates and values
  • Understand pathology results from prostatectomy including: primary & secondary Gleason grades, status of surgical margins, extracapsular extension, seminal vesicle involvement, lymph node involvement
  • Ask radiation oncologist the suggested radiation dose
  • Ask if androgen deprivation (ADT) is also suggested

Then, evaluate your “Progression Free Probability” after salvage radiation using the Stephenson, et al nomogram from Memorial Sloan Kettering

For a full discussion and links to nomograms, see:

 

After Radiation

After radiation, PSA does not normally reach undetectable because radiation is targeted to kill cancerous tissue while some normal prostate tissue survives. Further, the PSA does not drop immediately but decreases over an extended time (months or years) until it reaches a “nadir” (the lowest value ever achieved) and stabilizes. Despite these issues, the PSA is still useful for identifying recurrence. The current definition of PSA failure after radiation is an increase of 2 ng/mL above the nadir. You may also hear an older definition of 3 consecutive PSA rises taken 3 months apart after nadir is reached. Lee, et al. recently reported that “of men who have a rising PSA after definitive radiation, approximately 26% will have clinical evidence of a local recurrence, and 47% will develop distant metastases within five years”.[4]

Caution: “PSA Bounce” after radiation therapy
A phenomenon called PSA bounce (or PSA bump) frequently occurs after radiation therapy. It is defined as a temporary PSA increase after initial PSA drop. It is thought to be caused by radiation induced prostatitis.  According to the follow-up studies at SPI in Seattle and RCOG in Atlanta, the median time of occurrence after radiation is about 18 months (range 6-36 months). The abnormal PSA elevation can last from a few months to 18 months and the PSA increase is usually from 0.4 to 2.0 but in rare cases may be as high as 15.

A second local treatment may be beneficial if there is cancer remaining in the prostate bed. However, the risk of additive side-effects must be carefully considered. In our Nov. 2008 Insights, Dr. Paul Song wrote: “Patients most likely to benefit from salvage local therapy after primary radiotherapy are those with the following:

1. Pathologically documented local failure
2. No clinical or radiographic evidence of distant metastases
3. Life expectancy > 5 to 10 years based on age and health
4. Disease-free interval of >2 years
5. PSA < 10 at time of salvage
6. Long PSA doubling time (> 9 months)
7. Gleason score at salvage of 6 or less.

See: Salvage High Dose Rate Brachytherapy after Radiation

 

What are the local options after radiation?

More Radiation
The answer depends on the type and dose of radiation that was initially delivered. In many cases, the dose of the initial treatment may be considered near the maximum safe dosage. In other cases, a Radiation Oncologist may consider additional radiation with IMRT, stereotactic or brachytherapy (low-dose or high-dose).

See: Salvage Brachytherapy PDF

Prostatectomy
Salvage prostatectomy is a complex procedure that is available from a few highly experienced surgeons. Advances in radiation techniques have reduced the potential for surgical complications that in the past frequently required the additional removal of the bladder and/or the bowel. The risks of incontinence and impotence way exceed that of initial prostatectomy. Salvage prostatectomy should be restricted to men who are good surgical risks, have evidence of prostate cancer remaining in the prostate, have a low risk of cancer elsewhere and are willing to face the likelihood of severe incontinence.

Cryotherapy
Salvage cryotherapy is a standard procedure after radiation failure but the side-effects can also be significant, including incontinence.  However, in the hands of skilled practitioners, the risk of incontinence after salvage cryotherapy is certainly less than the risk of incontinence after salvage surgery.

See: Salvage Cryotherapy PDF

Which approach provides better survival?

There are few studies that provide results for salvage treatments and certainly no random comparisons. A report by Pisters LL, et al. that contrasted data from Mayo Clinic and MD Anderson provides the following insights. “There was no significant difference in disease specific survival (at 5 years salvage cryotherapy 96% vs salvage radical prostatectomy 98%, p = 0.283)”.[5]

 

After Cryotherapy, HIFU and others

After cryotherapy, HIFU, etc. the PSA will not, as a rule, be undetectable. For example, with cryo, a thin layer of prostate tissue is preserved along the urethra by the warming catheter. This will continue to produce a small amount of PSA which may tend to increase slowly over the years. The definition of recurrence is often debated but a rising PSA is cause for reevaluation and possibly re-biopsy. If cancer is detected in the prostate, Cryo (or HIFU) can be repeated. Radiation to the prostate is also an option. Salvage local treatments after Cryo are seldom reported due to the small number of men treated. In a review of 13 salvage treatments, Hepal, et al. concluded: “Full-dose intensity-modulated radiotherapy after cryotherapy is well tolerated, without excess late morbidity.”[6] Androgen deprivation is more commonly used for those with cancer that is progressing.

 

References:

1 Trock, et al. Johns Hopkins {AUA 2009 abstract 1285}
2 Zelefsky et al J Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer. Clin Oncol. 2005 Feb 1;23(4):826-31. Abstract
3 Stamey TA, et al: Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 317:909-916, 1987. Abstract
4 Lee WR, Hank GE, Hanlon A. Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: Clinical observations. J Clin Oncol 15:230-238, 1997. Abstract
5 Pisters LL, et al. Locally recurrent prostate cancer after initial radiation therapy: a comparison of salvage radical prostatectomy versus cryotherapy. J Urol. 2009 Aug;182(2):517-25; discussion 525-7. Epub 2009 Jun 13. Abstract
6 Hepel JT, et al. Intensity-modulated radiotherapy of the prostate after cryotherapy: initial experience. Urology. 2008 Dec;72(6):1310-4; Abstract
 

Page updated 9/6/11