Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration

doi:10.1016/j.eururo.2011.03.011

European Urology

Volume 60, Issue 2, August 2011, Pages 205-210

https://doi.org/10.1016/j.eururo.2011.03.011 Get rights and content

Abstract

Background

Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined.

Objective

To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP.

Design, setting, and participants

This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers.

Intervention

Open SRP.

Measurements

BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥0.1 or ≥0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death.

Results and limitations

Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31–43), 77% (95% CI, 71–82), and 83% (95% CI, 76–88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period.

Conclusions

In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP.

Introduction

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the United States [1]. Although local therapies with curative intent, such as primary radical prostatectomy (RP) and radiation therapy (RT), may result in durable cancer control in most cases, up to 30% of patients experience biochemical recurrence (BCR) [2], [3], [4]. Left untreated, more than a quarter of patients with BCR after RT develop local disease progression at 5 yr [5]. Historically, salvage RP (SRP) for men with biopsy-proven local recurrence after RT has rarely been performed because of concerns regarding lack of efficacy and high morbidity [5], [6], [7]. However, improvement in surgical experience has led to improved functional outcomes with lower side effects [8]. Furthermore, there is currently no established method of salvage local therapy after RT [9], [10], [11].

The efficacy of contemporary SRP and selection of appropriate candidates for SRP remain poorly investigated. Several single-center studies have investigated the efficacy of SRP for radiation-recurrent PCa [6], [7], [9], [12], [13], but conclusions from these studies were limited by their small sample size; single-center nature; and not assessing important end points, such as metastasis and cancer-specific death. Moreover, none of these studies was sufficiently powered to identify pre-SRP variables that could identify patients who could benefit from SRP. Thus, we performed a retrospective assessment of oncologic outcomes after SRP in a multicenter series of patients with radiation-recurrent PCa to identify predictors of post-SRP cancer control.

Section snippets

Study design and population

Seven participating sites provided information for men treated with SRP at their site. This was an institutional review board–approved study conducted according to the US Health Insurance Portability and Accountability Act guidelines. All institutions (Memorial Sloan-Kettering Cancer Center [MSKCC], Mayo Clinic, Netherlands Cancer Institute, San Raffaele Hospital, Katholieke Universiteit [KU] Leuven, University of Sao Paulo, and Vancouver General Hospital) shared agreements before the

Results

The 404 patients had a median age of 65 yr of age at the time of SRP (interquartile range [IQR]: 60–69), with a median pre-SRP PSA of 4.5 ng/ml (IQR: 2.5–7.4). Overall, the median time interval between RT and SRP was 41 mo (IQR: 27–58). Approximately half of the patients had a post-RT prostate biopsy Gleason score ≥7, and 25% were not graded because of RT treatment effect (Table 1). Clinical stage T3 cancer was present in 72 patients (18%) at the time of recurrence before SRP.

In analyzing SRP

Discussion

A critical concern in the management of men with rising PSA levels after RT for PCa is determining whether a rising PSA represents recurrence and whether this represents local and/or distant disease. If the recurrence is deemed localized, there is still the opportunity for cure with salvage therapy. SRP represents one such treatment approach. Stephenson et al. have previously shown in a large study that one-third of patients were free of disease progression 6 yr after salvage RT, suggesting

Conclusions

We demonstrated that a local salvage treatment such as SRP can lead to a considerable BCR-free and metastasis-free survival. With pre- and postoperative predictive models, we identified several features associated with BCR and metastasis after SRP. These improved selection criteria may help better stratify patients who would most benefit from SRP, thereby sparing them from ADT and potentially enhancing their QoL. The current study presents tools for estimating the probability of oncologic

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Cited by (175)

Salvage high-intensity focused ultrasound (S-HIFU) for recurrence after primary radiotherapy of prostate cancer
2024, French Journal of Urology
To evaluate functional and oncological outcomes of salvage high-intensity focal ultrasound (S-HIFU) after external beam radiotherapy (EBRT) failure in prostate cancer (PCa) patients.
This single-center study included patients who underwent S-HIFU for local recurrence after EBRT between 2006 and 2023. Cancer-specific survival, metastasis-free survival and progression-free survival were illustrated using Kaplan–Meier curves. Disease progression was defined by one of the following criteria: increase of 2 ng/mL or more above the PSA nadir, positive post-S-HIFU biopsy or initiation of androgen deprivation therapy (ADT). Multivariable Cox proportional hazards model was used to identify predictors of disease progression after S-HIFU.
A total of 52 S-HIFU sessions for 48 patients were performed. Median time between EBRT and S-HIFU was 6.5 years. Median PSA before S-HIFU was 3.2 ng/mL and median PSA nadir after S-HIFU was 0.58 ng/mL. A total of 39 (81.3%) complications was recorded, including 3 (6.3%) high grade complications according to the Clavien-Dindo classification. After a median follow-up period of 6 years, 14 (29.2%) patients developed metastatic disease. Eighteen (37.5%) patients had no recurrence, whereas 30 (62.5%) patients received ADT for disease progression. The estimated 5-yr cancer-specific survival (CSS), metastasis-free survival (MFS) and progression-free survival rates (PFSR) were 100%, 79.9% (95% CI 67–92) and 41.2% (95% CI 74–96), respectively. The estimated 10-yr CSS, MFS and PFSR were 80% (95% CI 45–100), 50.7% (95% CI 19.4–82.1) and 14% (95% CI 10.8–45), respectively. The hazard of progression increased with the intermediate (HR 3.8; 95% CI 0.99 to 15; p = 0.049) and high pre-EBRT d’Amico-s risk group (HR 4.1; 95% CI 0.98 to 16.2; p = 0.050). Also, the time between EBRT and S-HIFU was significantly associated with risk of progression (HR 0.61; 95% CI 0.43 to 0.86; p = 0.004). No significant difference linked to the disease progression (DP) risk was found between focal vs whole-gland treatment (p = 0.70).
Physicians should consider HIFU as a local salvage treatment after failed EBRT, thus avoiding or delaying palliative androgen deprivation therapy. Further studies are needed to improve patient selection for this therapy.
4.
Évaluer les résultats fonctionnels et oncologiques des ultrasons focaux de haute intensité (S-HIFU) de rattrapage après l’échec de la radiothérapie externe (RTE) chez les patients atteints de cancer de la prostate.
Cette étude monocentrique a porté sur des patients traités par HIFU pour une récidive locale après une radiothérapie externe entre 2006 et 2023. La survie spécifique au cancer, la survie sans métastase et la survie sans progression ont été illustrées à l’aide de courbes de Kaplan-Meier. La progression de la maladie a été définie par l’un des critères suivants : augmentation de 2 ng/mL ou plus par rapport au nadir du PSA [11], biopsie post-SHIFU positive ou initiation d’une thérapie de privation androgénique. Un modèle multivariable à risques proportionnels de Cox a été utilisé pour identifier les facteurs prédictifs de la progression de la maladie après les HIFU.
Au total, 52 séances d’HIFU ont été réalisées pour 48 patients. Le délai médian entre la RTE et les HIFU était de 6,5 ans. Le taux médian de PSA avant les HIFU était de 9 ng/ml et le taux médian de PSA au nadir après les HIFU était de 0,58 ng/mL. Au total, 39 (81,3 %) complications ont été enregistrées, dont 3 (6,3 %) de haut niveau selon la classification de Clavien-Dindo. Après une période médiane de suivi de 6 ans, il n’y a eu aucun décès dû à des causes autres que le cancer de la prostate. Quatorze patients ont développé une maladie métastatique. Dix-huit patients n’ont pas eu de récidive, tandis que 30 patients ont reçu une hormonothérapie de première génération en cas de progression de la maladie. Les taux estimés de survie spécifique au cancer, de survie sans métastase et de survie sans progression de la maladie sur 10 ans étaient respectivement de 80 % (IC à 95 % : 45–100), 50,7 % (IC à 95 % : 19,4–82,1) et 14 % (IC à 95 % : 10,8–45). Le risque de récidive augmentait avec les groupes de risque intermédiaire (HR 3,8 ; 95 % CI 0,99 à 15 ; p = 0,049) et élevé de D’Amico (HR 4,1 ; 95 % CI 0,98 à 16,2 ; p = 0,050). De même, le temps écoulé entre la RTE et les HIFU de rattrapage était significativement associé au risque de progression de la maladie (HR 0,61 ; 95 % CI 0,43 à 0,86 ; p = 0,004). Le type de traitement n’était pas significativement lié au risque de progression de la maladie.
Les médecins devraient considérer les HIFU comme un traitement de sauvetage local après l’échec de la RTE, ce qui permet d’éviter ou de retarder le traitement palliatif par privation androgénique. D’autres études sont nécessaires pour améliorer la sélection des patients pour cette thérapie.
4.
Long-term Outcomes and Patient Satisfaction Following Salvage Robot-assisted Radical Prostatectomy: A Modern Perspective
2024, European Urology Open Science
Approximately two-thirds of men who undergo primary treatment for prostate cancer (PC) will experience biochemical recurrence (BCR). Salvage robot-assisted radical prostatectomy (sRARP) offers curative treatment in this disease setting and men who choose this option may avoid palliative androgen deprivation therapy (ADT). The purpose of this study was to describe long-term outcomes and patient feedback following sRARP.
We reviewed data for consecutive men with biopsy-proven localized BCR who underwent sRARP and pelvic lymph node dissection at a single tertiary referral center between 2004 and 2021. Perioperative data, Clavien-Dindo complications, and functional outcomes were recorded. The Kaplan-Meier method was used to estimate prostate-specific antigen–free (≥0.2 ng/ml) survival (PSAFS) and metastasis-free survival (MFS). Three Likert-type items (score 1-5) from the validated Surgical Satisfaction Questionnaire-8 were distributed to patients postoperatively.
We included 78 men, of whom 72 (92%) had undergone primary radiotherapy and six (8%) had received primary prostate ablation. Median follow-up was 10.1 yr (interquartile range 5.8–12.4). Final pathology identified ≥pT3N0M0 in 35 patients (45%) and positive margins in 23 (29%). The overall complication rate was 50%. Of the 26 (33%) major (grade ≥III) complications, anastomotic stricture (32%) was most common. The estimated 3-, 5-, and 10-yr survival rates were 85.6% and 80.2%, 83.5% for PSAFS (n = 11), and 74.1%, 83.5%, and 70.5% for MFS (n = 23), respectively. At last follow-up, postoperative ADT had been administered to 17 patients (22%), and 39 men (50%) remained alive a decade after sRARP. Continence and potency were maintained in 33/62 (53%) and 1/16 (6%) patients, respectively. Thirty-five respondents (45%) reported median questionnaire scores (≥4) in favor of sRARP. Limitations include the small single-center series and a single query point for patient feedback.
Long-term outcomes of sRARP suggest that the technical challenges and morbidity of the procedure are qualified by patient feedback and the opportunity to evade the morbidity and mortality of biochemically recurrent PC.
We reviewed the cancer outcomes and side effects of robot-assisted surgical removal of the prostate after treatment failure with radiation or ablation for prostate cancer. We found that this type of treatment has substantial risks and long-term side effects, but the surgery provides an opportunity to cure prostate cancer and/or avoid the consequences of indefinite hormonal treatment. Overall, most men who underwent this surgery were not disappointed with their decision despite the higher risks and consequences.
Salvage Radical Prostatectomy for Recurrent Prostate Cancer After Primary Nonsurgical Treatment: An Updated Systematic Review
2023, European Urology Focus
Salvage radical prostatectomy (sRP) has historically been associated with high morbidity, whilst recently published multicentre series suggested a trend towards improved outcomes. Hence, we performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria to investigate the oncological and functional results and morbidity of sRP. We included 20 retrospective articles comprising 4175 men. Robotic procedures were performed in 40% and nerve sparing in up to 36% of men. Postoperative continence was preserved in 40.4% of patients and erectile function in <16%. High-grade complications were described in 6.6% of patients (rectal injuries 0.9%). At final sRP pathology, surgical margins were positive in 26.1%, 32.8% had seminal vesicle invasion, and International Society of Urological Pathology grade was >3 in 26.6%. Ten-year metastasis-free survival ranged from 72% to 77% and 5-yr cancer-specific survival ranged from 86.6% to 97.7%. Salvage radical prostatectomy shows durable oncological control and morbidity improved over recent years, despite remaining significant compared to and higher than that of primary radical prostatectomy.
Salvage radical prostatectomy (sRP) shows improving oncological control and morbidity over time. The complications associated with sRP and its functional results seem to be acceptable and are continuously improving.
Diagnosis of early biochemical recurrence after radical prostatectomy or radiation therapy in patients with prostate cancer: State of the art
2022, Diagnostic and Interventional Imaging
Biochemical recurrence after primary treatment in prostate cancer is not uncommon. A rising serum prostate-specific antigen level represents a first sign of disease relapse. At this time of low disease burden, imaging and particularly magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) are essential to determine the localization of the recurrence, which may be local, in lymph nodes, and/or metastatic. Imaging results allow best determine modalities of salvage treatment, which can be local by using radiotherapy or other focal treatments or systemic using hormonotherapy. Current evidence suggests that multiparametric magnetic resonance imaging, PET/CT with prostate specific membrane antigen and lympho-magnetic resonance imaging are effective and complementary to detect local recurrences and distant metastases.
Salvage High-Dose-Rate Brachytherapy for Recurrent Prostate Cancer After Definitive Radiation
2021, Practical Radiation Oncology
Salvage high-dose-rate brachytherapy (sHDRBT) for locally recurrent prostate cancer after definitive radiation is associated with biochemical control in approximately half of patients at 3 to 5 years. Given potential toxicity, patient selection is critical. We present our institutional experience with sHDRBT and validate a recursive partitioning machines model for biochemical control.
We performed a retrospective analysis of 129 patients who underwent whole-gland sHDRBT between 1998 and 2016. We evaluated clinical factors associated with biochemical control as well as toxicity.
At diagnosis the median prostate-specific antigen (PSA) was 7.77 ng/mL. A majority of patients had T1-2 (73%) and Gleason 6-7 (82%) disease; 71% received external beam radiation therapy (RT) alone, and 22% received permanent prostate implants. The median disease-free interval (DFI) was 56 months, and median presalvage PSA was 4.95 ng/mL. At sHDRBT, 46% had T3 disease and 51% had Gleason 8 to 10 disease.
At a median of 68 months after sHDRBT, 3- and 5-year disease-free survival were 85% (95% CI, 79-91) and 71% (95% CI, 62-79), respectively. Median PSA nadir was 0.18 ng/mL, achieved a median of 10 months after sHDRBT. Patients with ≥35%+ cores and a DFI <4.1 years had worse biochemical control (19% vs 50%, P = .02). Local failure (with or without regional/distant failure) was seen in 11% of patients (14/129), and 14 patients (11%) developed acute urinary obstruction requiring Foley placement and 19 patients (15%) developed strictures requiring dilation.
sHDRBT is a reasonable option for patients with locally recurrent prostate cancer after definitive RT. Those with <35%+ cores or an initial DFI of ≥4.1 years may be more likely to achieve long-term disease control after sHDRBT.
Comparison of salvage radical prostatectomy vs. salvage ablation therapy for biopsy-proven radio-recurrent localized prostate cancer
2024, Canadian Urological Association Journal

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Platinum Priority – Prostate CancerEditorial by Markus Graefen on pp. 211–213 of this issueSalvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration

Abstract

Background

Objective

Design, setting, and participants

Intervention

Measurements

Results and limitations

Conclusions

Introduction

Section snippets

Study design and population

Results

Discussion

Conclusions

Urol Oncol

Eur Urol

J Urol

Int J Radiat Oncol Biol Phys

Eur J Surg Oncol

J Urol

Eur Urol

Cancer statistics, 2010

CA Cancer J Clin

Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09

J Clin Oncol

Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: a comparison of clinical cohorts adjusted for case mix

J Clin Oncol

Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial

JAMA

Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations

J Clin Oncol

Platinum Priority – Prostate Cancer
Editorial by Markus Graefen on pp. 211–213 of this issue
Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration