Background: Radical external beam radiotherapy (EBRT) is a standard treatment for prostate cancer patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. For these patients, local salvage therapy such as radical prostatectomy, cryotherapy, and brachytherapy may be indicated. Objective: The objectives of this review were to analyze the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. Methods: A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. Results: Most studies demonstrated that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. Conclusions: Our results suggest that for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis. An improvement in selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological outcome and least comorbidity.

Biochemical recurrence (BCR) rates after primary external beam radiation therapy (EBRT) for prostate cancer have been reported to reach 63%. In 20-30% of the cases, these are local recurrences, which means patients could still benefit from local salvage therapy [1,2]. Nevertheless, only a small portion of these cases (0.9-2%) are actually managed with salvage radical prostatectomy (SRP), whereas most end up receiving castration therapy, regardless of the relapse being local or metastatic [1,3].

Careful patient selection is important to guide the decision-making process in the management of patients with local recurrence after EBRT failure. SRP, defined as a radical prostatectomy procedure performed for local failure after primary EBRT, has been refined over the past decade. Increasing surgical experience has resulted in a decrease in the rate of surgical complications. In addition, biochemical outcomes reported in recent series suggest a superiority of SRP over other salvage treatment modalities, such as cryotherapy, high-intensity focused ultrasound, or brachytherapy [4].

The aim of the present study is to provide a systematic evidence-based analysis of the current literature on SRP in patients with radiation-recurrent prostate cancer.

A systematic review of the literature was performed in July 2014 using the PubMed database ( Identification and selection of the studies was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria ( using the search term: ‘salvage radical prostatectomy'. Only studies specifically looking at the outcomes of SRP after failure of EBRT were considered for the present analysis. The level of evidence was reported as described by the Oxford Center for Evidence-Based Medicine ( Data related to the following topics were specifically analyzed: definition of BCR after EBRT and identification of local recurrence.

All of the reported series on SRP consider as a definition criterion for BCR three or more consecutive increases of prostate-specific antigen (PSA) after nadir, occurring at least 6 months after the nadir (previous ASTRO definition). More recent series have adopted the Phoenix ‘nadir + 2' definition (most recent ASTRO definition) [5]. This last criterion was conceived with the aim of ruling out patients with fluctuating PSA (approx. 25% of all EBRT-treated patients), thus preventing overtreatment [6]. However, two factors may potentially delay relapse diagnosis when adopting this ‘updated' definition: the lack of an ideal (or, at least, desired) PSA nadir value, and the need to obtain a ‘nadir + 2 ng/ml' level to consider the PSA elevation as BCR.

According to Zelefski et al. [7], the ideal nadir should be <0.5 ng/ml, as patients developing metastatic progression were found to have higher nadir values (mean of 2.2) than those with local relapse only (mean of 1.1). The nadir value after EBRT strongly correlates with different time points; thus, it should not be considered a value by itself but only a ‘time-dependent variable'. According to this group of investigators, ‘evaluation should be performed to rule out persistent local and systemic disease for patients with PSA nadir levels >1.5 ng/ml at 2 years', i.e. even without having reached the nadir +2 level.

In contrast, an increase in PSA of +2 greater than the nadir may potentially delay the diagnosis of disease failure, resulting in detrimental outcomes mostly in patients with local recurrence or persistence, as these patients can meanwhile develop metastatic progression. According to Stephenson et al. [8], this EBRT failure definition can delay the diagnosis by up to 5 years, thus minimizing the likelihood of a local salvage approach.

Hence, BCR after primary EBRT requires a more precise definition to improve the balance between the potential effects of delaying the detection of failure and the risk of overtreatment. Additional criteria, such as the timing [7,9] and pattern [10] of the PSA decrease after RT, may be more useful for characterizing and understanding the failure phenomenon.

The scenario is more complicated in the case of high-risk patients who have received EBRT with androgen deprivation therapy (ADT) [11]. These patients will more easily obtain very low nadir levels (close to 0 presumably due to ADT), but they might have higher metastatic risk. Three scenarios should be expected for these cases: (1) At 9-12 months after EBRT, ADT is stopped, and a low PSA kinetic BCR occurs; these patients have a higher probability of only local recurrence/persistence of the disease [12]. Thus, waiting until the PSA elevation reaches 2 ng/ml could be truly detrimental for any local salvage therapy. (2) After ADT suspension, a high PSA kinetic BCR occurs, indicating metastatic disease progression of a subclinical, yet micrometastatic, disease at presentation. (3) PSA elevation occurs during ADT, indicating a shift toward androgen independence, which is associated with a poor prognosis [13].

Once a BCR is recorded, criteria are necessary to identify potential candidates for local salvage therapy, where a local (vs. systemic) recurrence is most likely.

PSA kinetics can be useful for recognizing local recurrence or persistence of disease. A short PSA doubling time (<3 months) indicates a rapidly growing tumor, with a higher risk of clinical progression to metastatic disease [11]. A longer PSA doubling time (>6-10 months) is associated with a higher likelihood of local failure [14].

Local failure should be ideally proven by means of a biopsy, despite the reported false-positive (up to 60%) and false-negative (up to 20%) rates [15]. In the series by Vance et al. [16] the 2-year post-RT prostate biopsy was atypical or positive in 26% of cases, and it was statistically correlated with PSA level, demonstrating that post-RT prostate biopsy can be useful in identifying patients who are suitable for aggressive salvage therapy.

In contrast, Kaplan et al. [17] showed in their series of patients who underwent radical cystoprostatectomy at a median time of 60 months from EBRT that histological evidence of prostate cancer was present in 50% of patients with no BCR at the time of surgery. Although the biological significance of the presence of active prostate cancer cells in this selected population is uncertain, the study highlights the limitations of PSA in monitoring prostate cancer disease activity following definitive RT.

In other series, Gleason score-indefinable rates were present in 18-25% of cases [18,19]; current pathology guidelines discourage the use of Gleason scoring in specimens obtained from previously treated patients (ADT, as well as RT), as the induced histological changes could determine an apparently more clustered gland pattern. Markers of cell proliferation (such as Ki-67) could provide a more objective and reliable pathologic evaluation of post-RT prostate biopsies [15,20].

Imaging workups are ordered to exclude metastatic progression and often also to guide biopsy. New encouraging data have been obtained with dynamic contrast-enhanced MRI [21] and diffusion MRI imaging [22,23,24]. Moreover, for patients with PSA levels >2.5 ng/ml, 11C-choline PET has been reported to have a sensitivity of 89% and a positive predictive value of 72% [25,26]. Similarly, the sensitivity and specificity of 18F-choline PET in detecting bone metastases from prostate cancer were reported to be 79 and 97%, respectively [27,28]. Nevertheless, no consensus exists yet regarding the panel of imaging modalities to be performed to distinguish local from systemic recurrence.


Twenty-seven single-center or multicenter retrospective case series (level of evidence: 4) were reported on the use of SRP for radiorecurrent prostate cancer (table 1). In two series, the outcomes of SRP have been compared to those of other forms of salvage therapy (cryotherapy and brachytherapy).

Table 1

Oncological outcomes and complication rates of SRP series reported in the literature

Oncological outcomes and complication rates of SRP series reported in the literature
Oncological outcomes and complication rates of SRP series reported in the literature

The careful evaluation of SRP prognostic factors is of paramount importance for the appropriate selection of patients. Many retrospective studies and two high-quality literature reviews [29,30] have highlighted the main prognostic factors, which have emerged from retrospective univariate or multivariate analyses. As Chade et al. [30] have shown, the strongest prognostic factor was pre-SRP PSA, which was shown to often predict progression-free, cancer-specific or overall survival; evaluation of pre-SRP PSA should be followed by prostate biopsy Gleason scoring (although the data should be considered very carefully because of the objective difficulties in correctly and reproducibly scoring post-RT prostate needle specimens, as previously shown). Further prognostic factors, such as pre-RT clinical stage, percentage of positive cores at biopsy and PSA doubling time >12 months, have been reported to predict SRP clinical outcomes in fewer series.

Type of Surgery

The surgical salvage approach is not limited to SRP; pelvic exenteration [31], cystoprostatectomy [32,33,34,35,36,37,38], or prostatectomy with permanent cystostomy [39] can also be considered. The frequency of these demolition procedures was clearly decreased in the last published surgical salvage series because of the migration of the patients in the initial early stages as a result of an early diagnosis of disease relapse.

The median follow-up ranged from 12.5 to 120 months. The definition of BCR after SRP varies depending on the institution, but may be PSA >0.12 [39], >0.2 [6,37,40,41,42,43,44,45,46], or >0.4 ng/ml [32,47,48]. The reported BCR-free survival probability ranges between 28 and 93%. Because the BCR-free survival definition depends on the PSA nadir, it is also a time-dependent variable, and by plotting the reported BCR-free rates with the follow-up lengths of different series, a decreasing tendency can be observed (Spearman's rank correlation, 2-sided p = 0.05), which is clearly more significant (R2 = 58.5 vs. 15.7%, respectively) if only series with >40 patients are considered (fig. 1) [8,19,37,41,42,43,45].

Fig. 1

BCR-free survival rates plotted with the mean follow-up (a) and only in series with >40 patients (b).

Fig. 1

BCR-free survival rates plotted with the mean follow-up (a) and only in series with >40 patients (b).

Close modal

BCR-free rates are also correlated with the organ-confined disease (OCD) rates of the series (R2 = 14.2%); the significance of the correlation improves (R2 = 85.8%) if series with only >40 patients are considered (excluding the series by Chade et al. [19], which was too heterogeneous and multicentric and extended over a rather long [25 years] period) (fig. 2) [8,37,41,43,45,47,49]. The series published before 1995 had fewer patients than those published after 1998 (mean 27.8 vs. 62.7, not considering the series by Chade et al. [19] for the previously mentioned reasons; t test: p = 0.047), and the rate of OCD was clearly higher, thus confirming the migration of patients toward lower stages (30.75 vs. 47%; t test p = 0.02).

Fig. 2

BCR-free survival rates plotted with the mean OCD% (a) and only in series with >40 patients (b).

Fig. 2

BCR-free survival rates plotted with the mean OCD% (a) and only in series with >40 patients (b).

Close modal

The positive surgical margin rate decreased from an average of 47.5% before 1995 to an average of 20.8% after 1995 (Student's t test: p = 0.002). Even if a longer follow-up is associated with worse biochemical control, early diagnosis of recurrence (by determining higher OCD with lower positive surgical margin rates) will allow for higher BCR-free rates. In fact, the reported cancer-specific survival (CSS) has ranged from 70 to 83% at 10 years (table 1).

The Role of Lymph Node Dissection

Lymph node dissection (LND) associated with SRP was reported in only few series (table 1), and it was not standardized, which precludes both the assessment of its possible impact on CSS and any comparison among series.

In a completely different setting, Winter et al. [50] were the first to demonstrate, in a small series of 6 patients, the role of 11C-choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy, showing a complete permanent PSA remission without adjuvant therapy in 3 patients (median follow-up: 24 months, range: 21-35).

After 1 year, Rigatti et al. [51] showed that 24 out of 28 patients (85.7%) who received no adjuvant ADT after salvage LND had verified BCR after a mean follow-up of 38.9 months (median: 14.9), corresponding to a 5-year BCR-free survival rate of 19% (in only the ‘responder' subgroup).

Consequently, performing LND during SRP in LN-choline-PET-negative patients might have only a small impact on disease control.

Surgical Complications

Intraoperative complications and functional results have been quite stable over time, showing a slight (but not statistically relevant) improvement. The only relevant association was found by plotting the rectal injury rate and the blood loss (BL) against the OCD rate in different published series, and the results showed, as expected, that locally advanced disease exposes the patient to higher intraoperative risk, at least with regard to rectal injury (R2 = 19%) and BL (R2 = 54%).

The lower reported rates of BL in the last series were caused by the presence in the review of two series of robotic SRP [46,52,53]. The average rates of reported rectal injury, anastomotic stricture, and incontinence were 6.8, 18.3, and 47.8%, respectively.

The introduction of minimally invasive approaches (laparoscopy and robotic laparoscopy), themselves having evolved from SRP, has resulted in some advantages (table 2), at least with regard to the rates of overall and serious complications (Clavien >2).

Table 2

Minimally invasive SRP series: oncologic outcomes and complication rates

Minimally invasive SRP series: oncologic outcomes and complication rates
Minimally invasive SRP series: oncologic outcomes and complication rates

Thus, although difficult and challenging, SRP has been shown to present no relevant technical difficulties in high-volume centers. Moreover, it is also a ‘land of conquest' for minimally invasive approaches, e.g. robotic SRP [53,54].

Early diagnosis and appropriate selection of patients will improve oncologic results and decrease the intraoperative complication rate (BL and rectal injuries, which clearly depend on the disease stage). Concerning sexual function, erectile dysfunction (ED) is often present before SRP (table 3), and even in patients with residual sexual function after RT, it should not be a problem in this setting (i.e. post-RT failure). However, the most common salvage approach proposed in these cases is ADT, which is well known to induce ED. The CAPSURE data, which were recently analyzed and published by Agarwal et al. [1], showed that 93.5% of patients presenting with post-RT failure (including a relevant number with only local relapse) received and accepted castration therapy, despite the adverse effect of ED.

Table 3

ED and SRP: literature overview

ED and SRP: literature overview
ED and SRP: literature overview

Comparison with Other Local Salvage Modalities

Incontinence rates after SRP remain high (table 1), but this disadvantage must be weighed against the greatest and most durable obtainable biochemical control available and CSS; other apparently attractive salvage approaches, such as cryotherapy or high-intensity focused ultrasound are not free of (often serious) complications (table 4).

Table 4

Clinical outcome of main salvage cryotherapy and high-intensity focused ultrasound (a) and recently published SBT series (b)

Clinical outcome of main salvage cryotherapy and high-intensity focused ultrasound (a) and recently published SBT series (b)
Clinical outcome of main salvage cryotherapy and high-intensity focused ultrasound (a) and recently published SBT series (b)

Salvage brachytherapy (SBT) offers a realistic alternative to SRP (table 4). Plotting of the BCR-free rates with the lengths of the follow-ups of the different SBT series revealed the same time-dependent tendency. The BCR-FS decay was slightly faster than that observed for the surgical series (α = 0.49 vs. -0.35) (fig. 3).

Fig. 3

BCR-free survival decay after SBT.

Fig. 3

BCR-free survival decay after SBT.

Close modal

The superiority of SRP may be attributed not so much to a desirable positive effect of the associated LND on micrometastases (as previously shown, the data are insufficient to defend this theory), but rather to the peculiar pattern of tumor recurrence after RT [18], i.e. in the periurethral zone, which is generally spared during these approaches to minimize side effects [100].

SRP seems to offer durable oncologic outcomes while potentially avoiding systemic noncurative therapy. However, rather high rates of incontinence and ED are associated with the procedure. The main issue continues to be the early detection of post-RT failure, which could facilitate further improvement in long-term oncologic results. This reinforces the need for proper patient counseling and selection. Robot-assisted prostatectomy has been largely described over the last years, with some potential advantages that are related to the three-dimensional magnification vision and the more precise dissection. Promising new imaging tools could improve patient selection, thus avoiding the surgical morbidity associated with this type of challenging procedure.

The authors state that there are no conflicts of interest regarding the publications of this article.

Agarwal PK, Sadetsky N, Konety BR, Resnick MI, Carroll PR: Treatment failure after primary and salvage therapy for prostate cancer: likelihood, patterns of care, and outcomes. Cancer 2008;112:307-314.
Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Billiet I, Torecilla JL, Pfeffer R, Cutajar CL, Van der Kwast T, Collette L: External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomized study. Lancet Oncol 2010;11:1066-1073.
Grossfeld GD, Li YP, Lubeck DP, Broering JM, Mehta SS, Carroll PR: Predictors of secondary cancer treatment in patients receiving local therapy for prostate cancer: data from cancer of the prostate strategic urologic research endeavour. J Urol 2002;168:530-535.
Parekh A, Graham PL, Nguyen PL: Cancer control and complications of salvage local therapy after failure of radiotherapy for prostate cancer: a systematic review. Semin Radiat Oncol 2013;23:222-234.
Roach M III, Hanks G, Thames H Jr, et al: Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG- ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006;65:965-974.
Sengoz M, Abacioglu U, Cetin I, Turkeri L: PSA bouncing after external beam radiation for prostate cancer with or without hormonal treatment. Eur Urol 2003;43:473-477.
Zelefsky MJ, Shi W, Yamada Y, Kollmeier MA, Cox B, Park J, Seshan WE: Postradiotherapy 2-year prostate-specific antigen nadir as a predictor of long-term prostate cancer mortality. Int J Radiat Oncol Biol Phys 2009;75:1350-1356.
Stephenson AJ, Scardino PT, Bianco FJ Jr, DiBlasio CJ, Fearn PA, Eastham JA: Morbidity and functional outcomes of salvage radical prostatectomy for locally recurrent prostate cancer after radiation therapy. J Urol 2004;172:2239-2243.
de Crevoisier R, Slimane K, Messai T, Wibault P, Eschwege F, Bossi A, Koscielny S, Bridier A, Massard C, Fizazi K: Early PSA decrease is an independent predictive factor of clinical failure and specific survival in patients with localized prostate cancer treated by radiotherapy with or without androgen deprivation therapy. Ann Oncol 2010;21:808-814.
Delouya G, Kaufman G, Sylvestre MP, Nguyen TV, Bahary JP, Taussky D, Després P: The importance of an exponential prostate-specific antigen decline after external beam radiotherapy for intermediate risk prostate cancer. Cancer Epidemiol 2012;36:e137-e141.
D'Amico AV, Chen MH, Roehl KA, Catalona WJ: Identifying patients at risk for significant versus clinically insignificant post-operative prostate-specific antigen failure. J Clin Oncol 2005;23:4975-4979.
Akyol F, Ozyigit G, Selek U, Karabulut E: PSA bouncing after short term androgen deprivation and 3D-conformal radiotherapy for localized prostate adenocarcinoma and the relationship with the kinetics of testosterone. Eur Urol 2005;48:40-45.
Pister LL, D'Amico AV: Prostate cancer: salvage local treatment, course 104 IC. AUA Education and Research Inc. Annual Meeting, Atlanta, GA, 2006.
Kim-Sing C, Pickles T; Prostate Cohort Outcomes Initiative: Intervention after PSA failure: examination of intervention time and subsequent outcomes from a prospective patient database. Int J Radiat Oncol Biol Phys 2004;60:463-469.
Crook J, Malone S, Perry G, Bahadur Y, Robertson S, Abdolell M: Postradiotherapy prostate biopsies: what do they really mean? Results for 498 patients. Int J Radiat Oncol Biol Phys 2000;48:355-367.
Vance W, Tucker SL, de Crevoisier R, Kuban DA, Cheung MR: The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome. Int J Radiat Oncol Biol Phys 2007;67:828-833.
Kaplan DJ, Crispen PL, Greenberg RE, Chen DYT, Viterbo R, Buyyounouski MK, Horwitz EM, Uzzo RG: Residual prostate cancer following radiotherapy: a study of radical cystoprostatectomy specimens. Urology 2008;72:654-658.
Leibovici D, Chiong E, Pisters LL, Guo CC, Ward JF, Andino L, Prokhorova IN, Troncoso P: Pathological characteristics of prostate cancer recurrence after radiation therapy: implications for focal salvage therapy. J Urol 2012;188:98-102.
Chade DC, Shariat SF, Cronin AM, Savage CJ, Karnes RJ, Blute ML, Briganti A, Montorsi F, van der Poppel H, Joniau S, Godoy G, Hurtado-Coll A, Gleave ME, Dall'Oglio M, Srougi M, Scardino PT, Eastham JA: Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration. Eur Urol 2011;60:205-210.
Kestin LL, Goldstein NS, Vicini FA, Mitchell C, Gustafson GS, Stromberg JS, Chen PY, Martinez A: Pathologic evidence of dose-response and dose-volume relationships for prostate cancer treated with combined external beam radiotherapy and high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 2002;54:107-118.
Rouviere O, Valette O, Grivolat S, Colin-Pangaud C, Bouvier R, Chapelon JY, Gelet A, Lyonnet D: Recurrent prostate cancer after external beam. Management of biochemical recurrence radiotherapy: value of contrast-enhanced dynamic MRI in localizing intraprostatic tumor-correlation with biopsy findings. Urology 2004;63:922-927.
Kim CK, Park BK, Lee HM: Prediction of locally recurrent prostate cancer after radiation therapy: incremental value of 3T diffusion-weighted MRI. J Magn Reson Imaging 2009;29:391-397.
Giannarini G, Petralia G, Thoeny HC: Potential and limitations of diffusion-weighted magnetic resonance imaging in kidney, prostate, and bladder cancer including pelvic lymph node staging: a critical analysis of the literature. Eur Urol 2012;61:326-340.
Petralia G, Alessi S, Alconchel A, Summers P, Musi G, Matei V, De Cobelli O, Renne G, Bellomi M: Anterior prostatic tumours are difficult to diagnose without MRI. Ecancermedicalscience 2012;6:252.
Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, Matarrese M, Matei DV, De Cobelli F, Del Maschio A, Rocco F, Rigatti P, Fazio F: Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol 2003;169:1337-1340.
Ceci F, Castellucci P, Graziani T, Schiavina R, Brunocilla E, Mazzarotto R, Ntreta M, Lodi F, Martorana G, Fanti S: 11C-Choline PET/CT detects the site of relapse in the majority of prostate cancer patients showing biochemical recurrence after EBRT. Eur J Nucl Med Mol Imaging 2014;41:878-886.
Rinnab L, Simon J, Hautmann RE, Cronauer MV, Hohl K, Buck AK, Reske SN, Mottaghy FM: [(11)C]choline PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy. World J Urol 2009;27:619-625.
Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Hammer J, Loidl W, Pirich C, Fogelman I, Langsteger W: The use of F-18 choline PET in the assessment of bone metastases in prostate cancer: correlation with morphological changes on CT. Mol Imaging Biol 2010;12:98-107.
Hautman RE: Salvage radical prostatectomy (in German). Urologe A 2006;45:1260-1265.
Chade DC, Eastham J, Graefen M, Hud JC, Karnes RJ, Klotz L, Montorsi F, van Poppel H, Scardino PT, Shariat SF: Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. Eur Urol 2012;61:961-971.
Kamat AM, Huang SF, Bermejo CE, et al: Total pelvic exenteration: effective palliation of perineal pain in patients with locally recurrent prostate cancer. J Urol 2003;170:1868-1871.
Gheiler EL, Tefilli MV, Tiguert R, et al: Predictors for maximal outcome in patients undergoing salvage surgery for radio-recurrent prostate cancer. Urology 1998;51:789-795.
Rainwater LM, Zincke H: Radical prostatectomy after radiation therapy for cancer of the prostate: feasibility and prognosis. J Urol 1988;140:1455-1459.
Moul JW, Paulson DF: The role of radical surgery in the management of radiation recurrent and large volume prostate cancer. Cancer 1991;68:1265-1271.
Stein A, Smith RB, deKernion JB: Salvage radical prostatectomy after failure of curative radiotherapy for adenocarcinoma of prostate. Urology 1992;40:197-200.
Pontes JE, Montie J, Klein E, Huben R: Salvage surgery for radiation failure in prostate cancer. Cancer 1993;71:976-980.
Lerner SE, Blute ML, Zincke H: Critical evaluation of salvage surgery for radio-recurrent/resistant prostate cancer. J Urol 1995;154:1103-1109.
Ward JF, Sebo TJ, Blute ML, Zincke H: Salvage surgery for radiorecurrent prostate cancer: contemporary outcomes. J Urol 2005;173:1156-1160.
Pisters LL, English SF, Scott SM, Westney OL, Dinney CP, McGuire EJ: Salvage prostatectomy with continent catheterizable urinary reconstruction: a novel approach to recurrent prostate cancer after radiation therapy. J Urol 2000;163:1771-1774.
Amling CL, Lerner SE, Martin SK, Slezak JM, Blute ML, Zincke H: Deoxyribonucleic acid ploidy and serum prostate specific antigen predict outcome following salvage prostatectomy for radiation refractory prostate cancer. J Urol 1999;161:857-862; discussion 862-863.
Bianco FJ Jr, Scardino PT, Stephenson AJ, Diblasio CJ, Fearn PA, Eastham JA: Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy. Int J Radiat Oncol Biol Phys 2005;62:448-453.
Heidenreich A, Ohlmann C, Ozgür E, Engelmann U: Functional and oncological outcome of salvage prostatectomy of locally recurrent prostate cancer following radiation therapy (in German). Urologe A 2006;45:474-481.
Seabra D, Faria E, Dauster B, Rodrigues G, Fava G: Critical analysis of salvage radical prostatectomy in the management of radioresistant prostate cancer. Int Braz J Urol 2009;35:43-48.
Leonardo C, Simone G, Papalia R, Franco G, Guaglianone S, Gallucci M: Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy. Int J Urol 2009;16:584-586.
Paparel P, Cronin AM, Savage C, Scardino PT, Eastham JA: Oncologic outcome and patterns of recurrence after salvage radical prostatectomy. Eur Urol 2009;55:404-411.
Eandi JA, Link BA, Nelson RA, et al: Robotic assisted laparoscopic salvage prostatectomy for radiation resistant prostate cancer. J Urol 2010;183:133-137.
Rogers E, Ohori M, Kassabian VS, Wheeler TM, Scardino PT: Salvage radical prostatectomy: outcome measured by serum prostate specific antigen levels. J Urol 1995;153:104-110.
Sanderson KM, Penson DF, Cai J, et al: Salvage radical prostatectomy: quality of life outcomes and long-term oncological control of radiorecurrent prostate cancer. J Urol 2006;176:2025-2031; discussion 2031-2032.
Heidenreich A, Richter S, Thuer D, Pfister D: Prognostic parameters, complications, and oncologic and functional outcome of salvage radical prostatectomy for locally recurrent prostate cancer after 21st-century radiotherapy. Eur Urol 2010;57:437-445.
Winter A, Uphoff J, Henke RP, Wawroschek F: First results of [11C]choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy. Urol Int 2010;84:418-423.
Rigatti P, Suardi N, Briganti A, Da Pozzo LF, Tutolo M, Villa L, Gallina A, Capitanio U, Abdollah F, Scattoni V, Colombo R, Freschi M, Picchio M, Messa C, Guazzoni G, Montorsi F: Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol 2011;60:935-943.
Vallancien G, Gupta R, Cathelineau X, Baumert H, Rozet F: Initial results of salvage laparoscopic radical prostatectomy after radiation failure. J Urol 2003;170:1838-1840.
Zugor V, Labanaris AP, Porres D, Heidenreich A, Witt JH: Robot-assisted radical prostatectomy for the treatment of radiation-resistant prostate cancer: surgical, oncological and short-term functional outcomes. Urol Int 2014;92:20-26.
Rocco B, Cozzi G, Spinelli MG, Grasso A, Varisco D, Copelho RF, Patel V: Current status of salvage robot-assisted laparoscopic prostatectomy for radiorecurrent prostate cancer. Curr Urol Rep 2012;13:195-201.
Cheng L, Sebo TJ, Slezak J, et al: Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy. Cancer 1998;83:2164-2171.
Pisters LL, Perrotte P, Scott SM, et al: Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy. J Clin Oncol 1999;17:2514-2520.
Link P, Freiha FS: Radical prostatectomy after definitive radiation therapy for prostate cancer. Urology 1991;37:189-192.
Neerhut GJ, Wheeler T, Cantini M, Scardino PT: Salvage radical prostatectomy for radiorecurrent adenocarcinoma of the prostate. J Urol 1988;140:544-549.
Zincke H: Radical prostatectomy and exenterative procedures for local failure after radiotherapy with curative intent: comparison of outcomes. J Urol 1992;147:894-899.
Ahlering TE, Lieskovsky G, Skinner DG: Salvage surgery plus androgen deprivation for radioresistant prostatic adenocarcinoma. J Urol 1992;147:900-902.
Brenner PC, Russo P, Wood DP, Morse MJ, Donat SM, Fair WR: Salvage radical prostatectomy in the management of locally recurrent prostate cancer after 125I implantation. Br J Urol 1995;75:44-47.
Garzotto M, Wajsman Z: Androgen deprivation with salvage surgery for radiorecurrent prostate cancer: results at 5-year followup. J Urol 1998;159:950-954; discussion 954-955.
Darras J, Joniau S, Van Poppel H: Salvage radical prostatectomy for radiorecurrent prostate cancer: indications and results. Eur J Surg Oncol 2006;32:964-969.
Boris RS, Bhandari A, Krane LS, Eun D, Kaul S, Peabody JO: Salvage robotic-assisted radical prostatectomy: initial results and early report of outcomes. BJU Int 2009;103:952-956.
Stolzenburg JU, Bynens B, Do M, Rabenalt R, Katsakiori PF, Liatsikos E: Salvage laparoscopic extraperitoneal radical prostatectomy after failed high-intensity focused ultrasound and radiotherapy for localized prostate cancer. Urology 2007;70:956-960.
Nunez-Mora C, Garcia-Mediero JM, Cabrera-Castillo PM: Radical laparoscopic salvage prostatectomy: medium-term functional and oncological results. J Endourol 2009;23:1301-1305.
Kaouk JH, Hafron J, Goel R, Haber GP, Jones JS: Robotic salvage retropubic prostatectomy after radiation/brachytherapy: initial results. BJU Int 2008;102:93-96.
Strope SA, Coelho M, Wood DP, Hollenbeck BK: Robot-assisted salvage prostatectomy: evaluation of initial patient-reported outcomes. J Endourol 2010;24:425-427.
Chauhan S, Patel MB, Coelho R, et al: Preliminary analysis of the feasibility and safety of salvage robot-assisted radical prostatectomy after radiation failure: multi-institutional perioperative and short-term functional outcomes. J Endourol 2011;25:1013- 1019.
Masterson TA, Stephenson AJ, Scardino PT, Eastham JA: Recovery of erectile function after salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy. Urology 2005;66:623-626.
Gotto GT, Yunis LH, Vora K, Eastham JA, Scardino PT, Rabbani F: Impact of prior prostate radiation on complications after radical prostatectomy. J Urol 2010;184:136-142.
Pisters LL, Rewcastle JC, Donnelly BJ, et al: Salvage prostate cryoablation: initial results from the cryo on-line data registry. J Urol 2008;180:559-563; discussion 563-564.
Pisters LL, Leibovici D, Blute M, et al: Locally recurrent prostate cancer after initial radiation therapy: a comparison of salvage radical prostatectomy versus cryotherapy. J Urol 2009;182:517-525; discussion 525-527.
Perrotte P, Litwin MS, McGuire EJ, Scott SM, von Eschenbach AC, Pisters LL: Quality of life after salvage cryotherapy: the impact of treatment parameters. J Urol 1999;162:398-402.
Spiess PE, Katz AE, Chin JL, et al: A pretreatment nomogram predicting biochemical failure after salvage cryotherapy for locally recurrent prostate cancer. BJU Int 2009;106:194-198.
Williams AK, Martınez CH, Lu C, Ng CK, Pautler SE, Chin JL: Disease-free survival following salvage cryotherapy for biopsy-proven radio-recurrent prostate cancer. Eur Urol 2011;60:405-410.
Chin JL, Pautler SE, Mouraviev V, et al: Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications. J Urol 2001;165:1937-1942.
Miller RJ Jr, Cohen JK, Schuman B, Merlotti LA: Percutaneous, transperineal cryosurgery of the prostate as salvage therapy for post radiation recurrence of adenocarcinoma. Cancer 1996;77:1150-1154.
De la Taille A, Benson MC, Bagiella E, et al: Cryoablation for clinically localized prostate cancer using an argon-based system: complication rates and biochemical recurrence. BJU Int 2000;85:281-286.
Han KR, Belldegrun AS: Third-generation cryosurgery for primary and recurrent prostate cancer. BJU Int 2004;93:14-18.
Donnelly BJ, Saliken JC, Ernst DS, et al: Role of transrectal ultrasound guided salvage cryosurgery for recurrent prostate carcinoma after radiotherapy. Prostate Cancer Prostatic Dis 2005;8:235-242.
Ismail M, Ahmed S, Kastner C, Davies J: Salvage cryotherapy for recurrent prostate cancer after radiation failure: a prospective case series of the first 100 patients. BJU Int 2007;100:760-764.
Bahn DK, Lee F, Silverman P, et al: Salvage cryosurgery for recurrent prostate cancer after radiation therapy: a seven-year follow-up. Clin Prostate Cancer 2003;2:111-114.
Eisenberg ML, Shinohara K: Partial salvage cryoablation of the prostate for recurrent prostate cancer after radiotherapy failure. Urol 2008;72:1315-1318.
Ng CK, Moussa M, Downey DB, Chin JL: Salvage cryoablation of the prostate: followup and analysis of predictive factors for outcome. J Urol 2007;178:1253-1257.
Murat FJ, Poissonnier L, Rabilloud M, Belot A, Bouvier R, Rouviere O, Chapelon JY, Gelet A: Mid-term results demonstrate salvage high-intensity focused ultrasound (HIFU) as an effective and acceptably morbid salvage treatment option for locally radiorecurrent prostate cancer. Eur Urol 2009;55:640-649.
Uchida T, Shoji S, Nakano M, et al: High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after external beam radiation, brachytherapy or proton therapy. BJU Int 2011;107:378-382.
Beyer DC: Permanent brachytherapy as salvage treatment for recurrent prostate cancer. Urology 1999;54:880-883.
Grado GL, Collins JM, Kriegshauser JS, et al: Salvage brachytherapy for localized prostate cancer after radiotherapy failure. Urology 1999;53:2-10.
Wong WW, Buskirk SJ, Schild SE, et al: Combined prostate brachytherapy and short-term androgen deprivation therapy as salvage therapy for locally recurrent prostate cancer after external beam irradiation. J Urol 2006;176:2020-2024.
Allen GW, Howard AR, Jarrard DF, et al: Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option. Cancer 2007;110:1405-1416.
Nguyen PL, Chen MH, D'Amico AV, et al: Magnetic resonance image-guided salvage brachytherapy after radiation in select men who initially presented with favorable-risk prostate cancer: a prospective phase 2 study. Cancer 2007;110:1485-1492.
Lee HK, Adams MT, Motta J: Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. Brachytherapy 2008;7:17-21.
Aaronson DS, Yamasaki I, Gottschalk A, Speight J, Hsu IC, Pickett B, Roach M 3rd, Shinohara K: Salvage permanent perineal radioactive-seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy. BJU Int 2009;104:600-604.
Burri RJ, Stone NN, Pam Unger Z, Stock RG: Long-term outcome and toxicity of salvage brachytherapy for local failure after initial radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2010;77:1338-1344.
Mallick S, Dufour A, Fouques Y, Bensadoun H: Salvage therapy using high-intensity focused ultrasound for local recurrence of prostate cancer after radiation therapy (abstract). Eur Urol Suppl 2006;5:132.
Gelet A, Chapelon J, Poissonnier L, Bouvier R, Colombel M, Curiel L, et al: Local recurrence of prostate cancer after external beam radiation: early experience of salvage therapy using high-intensity focused ultrasound (abstract). Eur Urol Suppl 2006;5:133.
Philippou P, Yap T, Chinegwundoh F: Third-generation salvage cryotherapy for radio-recurrent prostate cancer: a centre's experience. Urol Int 2012;88:137-144.
Shimbo M, Inoue K, Koike Y, Katano S, Kawashima K: Salvage I seed implantation for prostate cancer with postradiation local recurrence. Urol Int 2013;90:294-300.
Izawa JI, Perrotte P, Greene GF, Scott S, Levy L, McGuire E, Madsen L, von Eschenbach AC, Pisters LL: Local tumor control with salvage cryotherapy for locally recurrent prostate cancer after external beam radiotherapy. J Urol 2001;165:867-870.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.