Salvage radical prostatectomy for recurrence of prostate cancer after radiation therapy

The goal of primary radiation therapy in the treatment of prostate cancer is to eradicate all of the local tumor. Although patients with relapsing disease after radiation therapy differ in their risk of death from prostate cancer, many will develop local progression, metastasis, and death. The recognition that local recurrence after radiation therapy portends a poor prognosis has led to the development of improved methods for early detection of recurrence and the development of alternative treatment strategies for radioresistant cancers. This article reviews knowledge regarding radiation failure and the role of salvage radical prostatectomy for men with local recurrence after radiation therapy for prostate cancer.     

Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy

Salvage radical prostatectomy is considered for patients with locally recurrent prostate cancer after external beam radiotherapy. Between 2001 and 2004, 32 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. We assessed the morbidity associated with this procedure and the outcome of the patients. Thirty-two patients underwent salvage radical prostatectomy. Initial pre-radiation median prostate-specific antigen was 13 ng/ml. Pre-radiation disease was clinical stage T1b in five cases, T2a in 10, T2b in 10 and T3a in seven. Mean operative time was 122 minutes, intraoperative blood loss was 550 ml and hospital stay and catheterization time were 5 and 12 days, respectively. There was biochemical failure in eight patients after salvage radical prostatectomy and 24 patients are biochemical non evidence of disease (bNED). In recurrent prostate local disease with prostate-specific antigen <10 ng/ml and life expectancy greater than 10 years, salvage radical prostatectomy is a reasonable treatment option.     

Review article Salvage surgery for locally recurrent prostate cancer after radiation therapy

Controversy exists regarding the optimal management of patients with an asymptomatic rising prostate specific antigen (PSA) level and locally recurrent adenocarcinoma of the prostate following definitive radiation therapy. Several treatment options may be offered in this clinical scenario, including salvage surgery, cryotherapy, watchful waiting, or androgen deprivation. Postradiation therapy patients whose residual disease is localized to the prostate may benefit from salvage surgery. Indeed, among all available options, only salvage surgery has been shown to result in long-term disease-free survival. However, treatment must be individualized according to clinical stage, serum PSA level before radiation and surgery, the medical condition of the patient, and expectations of the physician and patient. Herein, we review the available literature and our own experience with salvage surgery for radio-recurrent prostate cancer.     

Defining recurrence after radiation for prostate cancer

PURPOSE: We reviewed prostate specific antigen (PSA) definitions of recurrence after external beam radiation for prostatic cancer and related them to the definitions used for other treatment modalities. MATERIALS AND METHODS: The literature on defining recurrence after external beam radiation, brachytherapy and prostatectomy for prostate cancer was reviewed through a MEDLINE search to ensure completeness and the inclusion of all pertinent information. RESULTS: Although the definition, which is the current standard for estimating recurrence after external beam radiation, has proved to be a reasonable measure, alternative options that are more sensitive and specific have now been defined. Similar statistical testing and comparison must also be done for other treatment modalities since the choice of failure definitions has not been evaluated nearly as thoroughly for these therapies. As much as possible, outcome reporting should be done according to the same method to ensure fairness when comparisons are made. However, inherent differences between treatment modalities and their effect on PSA production must also be considered. CONCLUSIONS: With the latest available information from patients with long-term followup PSA definitions of tumor recurrence after external beam radiation for prostatic cancer must again be reviewed in a consensus conference format. The application of a universal PSA definition of tumor recurrence across multiple treatment modalities should also be explored.     

Salvage surgery for locally recurrent prostate cancer after radiation therapy: tricks of the trade

Biochemical recurrence after either radical prostatectomy or radiation therapy of prostate cancer will develop in an estimated 50,000 U.S. men. Salvage therapy has the potential of curing an isolated local recurrence of prostate cancer, however, this comes at the cost of potential morbidity. Salvage surgery after primary radiotherapy is technically demanding, and surgical expertise is necessary to optimize treatment outcomes while minimizing the inherent risks of the operation. Over the last decade, we have developed a substantial experience in salvage surgery for locally recurrent prostate cancer, and have developed key technical points and innovations that include primary closure of the bladder neck, bladder augmentation, and catheterizable urinary reconstruction using a Monti or Mitrofanoff procedure as a method of reducing the risks of postoperative urinary incontinence. We hope this review will provide the surgical oncologist and urologist with the important considerations that must be considered in salvage surgery. In addition, we discuss the importance and surgical details of using a well-vascularized rectus flap as a method of reducing perioperative morbidity.     

Salvage cryoablation for local recurrence of prostatic cancer after curative therapy

PurposeThe purpose of this study was to determine the efficacy of salvage cryotherapy for intra-prostatic and local extraprostatic recurrences after curative treatment of prostate adenocarcinoma.Material and methodTwenty-eight men (mean age, 69 ± 6 [SD] years; range: 51–82 years) treated with cryoablation for prostatic (N = 21) or extraprostatic (N = 7) recurrent prostate cancer after radiotherapy with or without associated prostatectomy were included. Technical success, complication and recurrences were reported. Biological recurrence was defined as an elevation ≥ 2 ng/mL of prostate specific antigen (PSA) serum level after the treatment.ResultsThe mean follow-up was 18 months. Among the 21 patients with intraprostatic recurrence, 14 had successful cryotherapy with a mean decrease in serum prostate-specific antigen (PSA) levels of ? 5.7 ± 2.6 (SD) ng/mL (range: ? 2.1 to ? 16.9 ng/mL). Four patients (19%) had early progression and three patients (14%) had delayed biological recurrence (mean time: 15 months). Among the 7 patients with extraprostatic recurrence, 2/7 (291%) had successful cryotherapy with a decrease in PSA serum level of ? 2.7 ± 1.6 (SD) ng/mL (range: ? 0.5–? 5.5 ng/mL) and 4/7 (57%) had early biological recurrence after cryotherapy that required androgen deprivation therapy, whereas 1/7 (4%) was lost to follow-up. No major complications were observed for both intra- and extraprostatic recurrence.ConclusionSalvage cryoablation of locally recurrent prostate cancer after curative treatment is feasible and safe when the half prostate is treated. It could delay initiation of androgen deprivation therapy in these patients.     

Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radiotherapy - preliminary results

Study Type – Prognostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There have been no reports on the application of HDR‐BT in Japan as salvage therapy for recurrence following radiotherapy. Our data showed that salvage HDR‐BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy. OBJECTIVE

• ? To assess the preliminary clinical results of salvage high‐dose‐rate brachytherapy (HDR‐BT) applied in cases of suspected local recurrence or of residual tumour after radiotherapy.

PATIENTS AND METHODS

• ? The subjects were 11 patients who met the above conditions and underwent salvage HDR‐BT between December 2006 and January 2009. The T stage at the initial treatment was T1c in three patients, T2 in three patients and T3 in five patients.
• ? Ten patients received HDR‐BT ± electron beam radiation therapy and one patient received proton beam irradiation.
• ? Follow‐up after the completion of salvage HDR‐BT lasted 18–41 months (mean 29 months). A dose of 11.0 Gy radiation was delivered twice (22.0 Gy in total), separated by a 6‐h interval, on the day the applicators were inserted.

RESULTS

• ? Seven of the 11 cases remained in a biochemical non‐evidence of disease state.
• ? The prostate‐specific antigen (PSA) level continuously rose after salvage HDR‐BT in three of the four other cases. Hormone administration was initiated in the four cases of PSA recurrence.
• ? No G3 or more severe events occurred, and the incidence of G2 was low during this study period.

CONCLUSION

• ? Of the 11 cases treated with salvage HDR‐BT, PSA levels remained low in seven cases and the incidence of complications was also low. This suggests that salvage HDR‐BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy.

     

Obesity as a predictor of biochemical recurrence and survival after radiation therapy for prostate cancer

OBJECTIVE: Obesity has been demonstrated to predict biochemical progression in men undergoing radical prostatectomy for prostate adenocarcinoma, and is associated with a higher risk of biochemical and clinical relapse after radiation therapy (RT). We evaluated if obesity, determined by body mass index (BMI), is associated with adverse disease characteristics, pre-treatment serum testosterone, biochemical disease free survival (bDFS), disease-specific survival (DSS), or overall survival (OS) in patients undergoing radical external beam radiation therapy for prostate cancer. PATIENTS AND METHODS: A cohort of 706 patients with localized prostate adenocarcinoma treated with RT between 1993 and 2001 were categorized as obese (BMI > or = 30 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) or normal (BMI < 25 kg/m(2)). The association between BMI, disease characteristics, and progression were evaluated by Chi-square and ANOVA tests, Kaplan-Meier survival analysis, and Cox regression analysis. RESULTS: 195 patients (27.6%) were normal weight, 358 (50.7%) were overweight and 153 (21.7%) were obese. Obese men had lower serum testosterone levels than overweight and normal-weight men (means 12.8, 14.1, and 15.7 nmol/L, respectively; p < 0.001). The BMI groups did not differ in Gleason score, pretreatment PSA, or stage. On multivariate analysis, BMI group was predictive of reduced bDFS (p = 0.02) and DSS (p = 0.008), with a trend toward reduced OS (p = 0.062). CONCLUSION: Obesity was associated with lower serum testosterone levels but not with adverse pretreatment pathological features. Obese men have a higher risk of biochemical recurrence and prostate-cancer specific death after RT.     

Radical prostatectomy after definitive radiation therapy for prostate cancer

Radical prostatectomy was performed in 14 patients following local failure of radiation therapy for adenocarcinoma of the prostate. Ten patients were treated with external beam and 4 with interstitial radiation. The interval from beginning radiation therapy to biopsy-proved residual or recurrent disease was twenty-four to one hundred fourteen months (mean 61 months). Ten patients had significant anterior and lateral fibrosis. Five patients had loss of tissue planes between the prostate and rectum, however, no rectal injuries occurred. Estimated blood loss was 300-8,000 cc (median 1,000 cc). Operative time was one hundred ten to three hundred seventy-five minutes (median 185 minutes). Significant late complications are impotence (100%) and incontinence (55%). Tumor volume was 1.1-27.2 cc (mean 11.1 cc). Seven patients had seminal vesicle involvement, 9 had level III capsule penetration, and 6 had positive surgical margins. Follow-up ranges from one to fifty-two months (median 18 months). Currently, 6 patients are clinically without disease and have serum prostate-specific antigen (PSA) of 0.0 ng/mL. Four patients have no clinical evidence of disease but do have detectable serum PSA, and 4 patients have evidence of metastatic bone disease on bone scan with elevated serum PSA levels. Radical prostatectomy following radiation therapy has no greater immediate morbidity or mortality compared with radical prostatectomy without prior irradiation and takes only slightly longer to perform. However, there is a marked increased risk of impotence and incontinence. More patients followed for a longer time are needed to assess the benefit of radical prostatectomy on survival of patients who fail radiation therapy.     

Hormonal therapy options for biochemical recurrence of prostate cancer after local therapy

Recurrence after local prostate cancer treatment detectable only by a rise in serum prostate specific antigen (PSA) is a very common problem facing clinicians. Given that the majority of these men are relatively young and otherwise healthy, treatment of PSA-only recurrence requires approaches that not only improve survival but also preserve quality of life. For radical prostatectomy patients, a PSA-only recurrence is broadly defined as persistent or rising PSA in the postoperative period. For radiation-treated patients, the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify three consecutive elevations of PSA after the post-treatment nadir PSA is achieved. Traditional hormonal therapy is the mainstay of systemic treatment for PSA-only recurrence, although nontraditional approaches such as intermittent and oral-only hormonal therapy are under study.     

Underutilization of local salvage therapy after radiation therapy for prostate cancer

ObjectiveTo evaluate the rates at which patients are offered and receive local salvage therapy (LST) after failure of primary radiotherapy for localized prostate cancer, as it is the only potentially curative treatment for localized recurrence but appears to be underutilized when compared with androgen-deprivation therapy (ADT) or observation.Materials and methodsPatients with localized prostate cancer who received primary radiotherapy with curative intent between 1999 and 2000 were identified in the British Columbia Tumour Registry. Exclusion criteria included patient age >72 years, prostate-specific antigen>40 ng/ml, and clinical stage T4 at diagnosis. Data on clinicopathologic features, primary therapy, prostate-specific antigen kinetics, and salvage therapy were collected retrospectively. Radiation failure was defined as biochemical recurrence according to the Phoenix criteria or by initiation of salvage therapy.ResultsOf 1,782 patients treated in the study period, 1,067 met inclusion criteria. Of these, 257 failed radiation therapy. Radiation therapy failure was managed with observation (>12 mo) in 126 patients and ADT in 119. Of the observed patients, 66 subsequently received ADT. Five patients (1.8%) received LST (3 radical prostatectomy and 2 brachytherapy).ConclusionsOnly 2% of patients relapsing after radiation therapy for localized prostate cancer received LST. Although the benefits of LST are unproven, these findings reveal a possible underutilization of LST and indicate a need for enhanced collaboration between specialties to optimize care of this challenging cohort.