Cancer Control and Complications of Salvage Local Therapy After Failure of Radiotherapy for Prostate Cancer: A Systematic Review

doi:10.1016/j.semradonc.2013.01.006

Seminars in Radiation Oncology

Volume 23, Issue 3, July 2013, Pages 222-234

https://doi.org/10.1016/j.semradonc.2013.01.006 Get rights and content

The National Comprehensive Cancer Network guidelines currently endorse salvage local therapy as a reasonable alternative to observation or androgen-deprivation therapy for select men with a biopsy-proven local recurrence after definitive radiation for prostate cancer. Patients being considered for salvage therapy should have had localized disease at presentation, a prostate-specific antigen < 10 at recurrence, a life expectancy >10 years at recurrence, and a negative metastatic workup. In this systematic review, we synthesize the current literature describing the oncologic efficacy and toxicity profile of salvage brachytherapy, prostatectomy, cryotherapy, and high-intensity focused ultrasound. We found 5-year biochemical control rates to be similar across treatments, in the range of 52%-56%, although patient selection and definition of failure was variable. Toxicity profiles were also distinct between local salvage modalities.

Section snippets

Search Strategy

We reviewed PubMed citations between January 1, 1990 and September 1, 2011. We combined the search terms “salvage and recurrent” and “prostate and high intensity focused ultrasound” or “prostate and cryotherapy,” or “prostatectomy and radiation,” or “prostate and brachytherapy” for 4 separate searches. We also searched the citations in 4 recent prior reviews on salvage treatments6, 7, 8, 9 to ensure a comprehensive search of relevant series. We included only original studies published in

Oncologic Outcomes of Salvage Brachytherapy

The literature synthesis for salvage brachytherapy is listed in Table 1. Most salvage brachytherapy reported in the literature has been performed with low-dose rate (LDR) permanent seed implants. The largest published series remains that from Grado et al published in 1999 and includes 49 patients with a median follow-up of 64 months and a 5-year-FFS rate of 34% using 2 rises above the nadir as the definition of failure.¹⁶ However, the FFS rate observed from Grado is somewhat lower than what has

Oncologic Outcomes of Salvage Radical Prostatectomy

The literature synthesis for salvage prostatectomy is listed in Table 2. The largest series published to date comes recently from Chade et al, and included 404 patients treated since 1985 across several institutions, including Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Netherlands Cancer Institute, San Raffaele Hospital, Katholieke Universiteit Leuven, University of Sao Paulo, and Vancouver General Hospital.²⁶ With a median follow-up of 4.4 years, 5-year bDFS was 48%, with failure

Oncologic Outcomes

The literature synthesis for salvage cryotherapy is listed in Table 3. A major challenge in the study of salvage cryotherapy remains the wide variation in definition of PSA control and the lack of a widely accepted definition for biochemical disease progression. The largest series published to date is a multi-institutional study from the COLD registry, including 279 patients from Pisters et al.⁵³ Using the ASTRO definition, 5-year bDFS was 58.9%, with a median follow-up time of 21.6 months. The

Oncologic Outcomes of Salvage HiFU

The literature synthesis for salvage HiFU is in Table 4. Although still a relatively new treatment in the salvage setting, recent studies have helped shed some light on a therapy still considered investigational in the USA. The largest cohort to date comes from Murat et al in France and includes 167 patients with a mean follow-up of 18 months.⁶⁹ Using a definition for failure as the PSA nadir + 2 (Phoenix definition), the 3-year progression-free survival rate was 53%. Similarly, Uchida et al

Discussion

In this review, we synthesized the literature on the oncologic outcomes and complications of salvage local therapies for recurrent prostate cancer after prior radiation therapy. Although the standard of care for these patients has typically been observation followed by ADT, 2 recent randomized trials of ADT alone vs ADT plus radiation in the definitive setting found that local therapy improves OS for men with locally advanced prostate cancer and provides a rationale to reconsider salvage local

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Cited by (54)

A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER)[Formula presented]
2021, European Urology
Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.
To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low–dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.
We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.
A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.
Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.
In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
The Case for Brachytherapy: Why It Deserves a Renaissance
2021, Advances in Radiation Oncology
Citation Excerpt :
A recent phase 2 trial, as well as several retrospective studies, demonstrated excellent rates of cancer-free and biochemical recurrence-free survival with brachytherapy and had acceptable, predominantly grades 1 and 2 gastrointestinal and genitourinary toxicity.51-53 Compared with other local salvage techniques, such as prostatectomy, high-frequency ultrasound, or cryotherapy, prostate brachytherapy has similar rates of biochemical control at 5 years with lower toxicity rates, such as incontinence and bladder neck stricture.54 Prostate brachytherapy remains a viable treatment option for patients, provides excellent outcomes with acceptable toxicity, and is cost effective.
The recent global events related to the coronavirus disease of 2019 pandemic have significantly changed the medical landscape and led to a shift in oncologic treatment perspectives. There is a renewed focus on preserving treatment outcomes while maintaining medical accessibility and decreasing medical resource utilization. Brachytherapy, which is a vital part of the treatment course of many cancers (particularly prostate and gynecologic cancers), has the ability to deliver hypofractionated radiation and thus shorten treatment time. Studies in the early 2000s demonstrated a decline in brachytherapy usage despite data showing equivalent or even superior treatment outcomes for brachytherapy in disease sites, such as the prostate and cervix. However, newer data suggest that this trend may be reversing. The renewed call for shorter radiation courses based on data showing equivalent outcomes will likely establish hypofractionated radiation as the standard of care across multiple disease sites. With shifting reimbursement, brachytherapy represents the pinnacle in hypofractionated, conformal radiation therapy, and with extensive long-term data in support of the treatment modality brachytherapy is primed for a renaissance.
Long-term results of a protocol-based ultrasound-guided salvage brachytherapy as re-irradiation for local recurrent prostate cancer
2020, Radiotherapy and Oncology
Citation Excerpt :
Comparing our results to the best salvage-prostatectomy series with a rate of rectal injury of 3.6% [19,30], in our analysis we only observed rectal injury in a single patient (1/82, 1.2%). In terms of urinary incontinence rates, the majority of analyses looking at salvage prostatectomy report rates between 18 and 58% [4,23,29,30–32]. This incidence is considerably higher than our reported results – we observed urinary incontinence only in 15/82 patients (18.3%).
To assess the long-term results of protocol-based ultrasound-guided salvage pulsed-dose rate brachytherapy in locally recurrent prostate cancer following previous radiation therapy.
A total of 82 patients (median age 69 years) with locally recurrent prostate cancer after previous external beam radiation therapy (43/82, 52.4%), prostatectomy and adjuvant radiation therapy (24/82, 29.3%) or brachytherapy (15/82, 18.3%) were treated with sole salvage interstitial pulsed-dose rate brachytherapy (PDR-BT). The treatment regimen consisted of two PDR-BT sections with 30 Gy (single pulse dose 0.6 Gy/h, 24 h per day) each up to a total reference dose of 60 Gy (EQD2 = 71.5 Gy-eq). The endpoints of the present analysis are cumulative local recurrence-rate, PSA-free survival, overall survival and the treatment-associated late toxicity according to the “Common Toxicity Criteria” with a median follow-up of 49 months (range, 12–129 months).
The 5-y. overall cumulative local recurrence rate was 17.7% with no significant differences between low, intermediate and high-risk groups. Differences in PSA-free survival were marginally non-significant, at 67.3%, 70.4% and 63.8% for low, intermediate and high risk group, respectively. No grade 3 gastrointestinal late side effects have been observed. The most common late side effect was urinary incontinence grade 1–3 and urinary frequency/urgency grade 1–3 in 18.3% (15/82) and 17.1% (14/82) of patients, respectively.
PDR salvage brachytherapy in local recurrent previously irradiated prostate cancer is efficient with low late toxicity. Salvage-brachytherapy represents a valuable therapeutic option for the treatment of previously irradiated locally recurrent prostate cancer.
Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019[Formula presented]
2020, European Urology
Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.
To present the results from the APCCC 2019.
Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.
The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.
Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.
These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.
The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
Focal Salvage MR Imaging–Guided Cryoablation for Localized Prostate Cancer Recurrence after Radiotherapy: 12-Month Follow-up
2020, Journal of Vascular and Interventional Radiology
Citation Excerpt :
This is in contrast to the results after SRP. A systematic review averaging the results of 24 studies reported incontinence in 50%, bladder neck stricture in 26%, rectal injury in 5%, and rectal fistula in 2.4% of patients after SRP (29). This study reported an incontinence rate of 3.2%, 1 urethral stricture (1.6%) needing surgical intervention, no rectal injury, and 3 rectal fistulas (4.8%), which were conservatively treated and resolved or diminished within a few months.
To evaluate safety, quality of life (QoL), and local cancer control after focal salvage MR imaging–guided cryoablation in patients with local recurrence of prostate cancer (PCa) after radiotherapy.
A retrospective, single-center study was performed in 62 patients with radiorecurrent PCa who underwent MR imaging–guided cryoablation since May 2011 with a follow-up ≥12 months in December 2017. Rates and descriptions of adverse events were reported. Ablation complications were classified according to the Clavien and SIR systems. Validated questionnaires were used to observe functional outcomes and QoL before therapy and 6 and 12 months after therapy. Cancer control was defined as no biochemical failure according to Phoenix criteria and no other clinical evidence for local or metastatic disease.
All procedures were technically feasible. The number of complications requiring major therapy (Clavien grade 3b/4 or SIR grade D/E/F) was low (2 [3.2%] and 1 [1.6%], respectively). After 12 months, the International Consultation of Incontinence Questionnaire–Short Form (P < .001) and 5-item International Index of Erectile Function (P = .001) scores became significantly worse, indicating increased symptoms of incontinence and diminished erectile function, without compromising QoL. Six patients developed metastases within 6 months. After 12 months, 36 patients (63%) were disease-free.
Focal salvage MR imaging–guided cryoablation is safe and is associated with a high technical success rate, preservation of QoL, and local PCa control. This treatment can be a reasonable alternative to salvage radical prostatectomy in properly selected patients with low morbidity and preservation of QoL; however, longer follow-up is needed.
Salvage brachytherapy for radiorecurrent prostate cancer: Searching for safety and success
2017, Brachytherapy

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: Dr. Nguyen has consulted for Ferring, Inc. The other authors declare no conflict of interest.

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Cancer Control and Complications of Salvage Local Therapy After Failure of Radiotherapy for Prostate Cancer: A Systematic Review

Section snippets

Search Strategy

Oncologic Outcomes of Salvage Brachytherapy

Oncologic Outcomes of Salvage Radical Prostatectomy

Oncologic Outcomes

Oncologic Outcomes of Salvage HiFU

Discussion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Eur Urol

Clin Oncol (R Coll Radiol)

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Brachytherapy

Brachytherapy

Urology

Int J Radiat Oncol Biol Phys

Urology

J Urol

J Urol

Eur Urol

J Urol

J Urol

Urology

J Urol

Int J Radiat Oncol Biol Phys

J Urol

Urology

Urology

J Urol

Urology

Eur J Surg Oncol

J Urol

J Urol

J Urol

J Urol

Eur Urol

J Urol Oct

Clin Prostate Cancer

J Urol

Urology

J Urol

J Urol

Urology

Eur Urol