A Prospective Study of Magnetic Resonance Imaging-guided Focal Salvage High-dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: Updated Results of 30 Patients

PurposeLimited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data.Methods and MaterialsPatients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used.ResultsThirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed.ConclusionsFocal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.     

High dose rate iridium-192 brachytherapy as a component of radical radiotherapy for the treatment of localised prostate cancer

AimsTo assess the treatment outcomes and toxicity of conformal high dose rate (HDR) brachytherapy boost as a means of radiation dose escalation in patients with localised prostate cancer.Materials and methodsBetween December 1998 and July 2004, 65 consecutive patients with localised prostate cancer (magnetic resonance imaging-staged T1–3 N0 M0) were treated with external beam radiation therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The patients selected this treatment modality in preference to entering an ongoing randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA) and Gleason score were included. The primary end point was biochemical disease-free progression. Late treatment-related morbidity was graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria.ResultsThe median patient age was 67.3 years (range 47.9–80). Sixty patients (92.3%) had intermediate- to high-risk disease defined by clinical stage, presenting PSA and Gleason score/World Health Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6–5.8), two patients had died of metastatic disease and another four patients had PSA relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%. Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal toxicities were observed.ConclusionsThese results suggest that the combined modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality with acceptable acute and late toxicities, comparable with those of EBRT alone. It offers an attractive conformal treatment modality with the potential of further dose escalation in the treatment of localised prostate cancer.     

Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: the University of California-San Francisco experience

PURPOSE: The aim of this study was to evaluate the feasibility and safety of salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer after external beam radiotherapy (EBRT). METHODS AND MATERIALS: We retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR brachytherapy for locally recurrent prostate cancer after EBRT between November 1998 and December 2005. After pathologic confirmation of locally recurrent disease, all patients were treated with 36 Gy in six fractions using two transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven patients received neoadjuvant hormonal therapy immediately presalvage, whereas none received adjuvant hormonal therapy postsalvage. Median follow-up time from recurrence was 18.7 months (range, 6-84 months). Determination of subsequent biochemical failure after brachytherapy was based on the definition by the American Society for Therapeutic Radiology and Oncology. RESULTS: Based on the Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three patients developed Grade 3 genitourinary toxicity. Maximum observed gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2-year Kaplan-Meier estimate of biochemical control after recurrence was 89%. Thirteen patients have achieved a PSA nadir < or =0.1 ng/ml, but at the time of writing this endpoint has not yet been reached for all patients. All patients are alive; however 2 have experienced biochemical failure, both with PSA nadirs > or =1, and have subsequently been found to have distant metastases. CONCLUSIONS: Salvage HDR prostate brachytherapy appears to be feasible and effective.     

Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival

Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10-40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61. 2 years underwent radical retropubic prostatectomy. Levels < or = 0.01 ng ml-1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml-1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6-70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir < or = 0.01 ng ml-1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy.     

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer

AimsThe safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup.Materials and methodsIn total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35–37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria.ResultsForty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively.ConclusionSBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a).     

Salvage reirradiation for local prostate cancer recurrence after radiation therapy. For who? When? How?

PurposeLiterature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer.Materials and methodsA total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47 months for low-dose-rate brachytherapy, 36 months for high-dose-rate brachytherapy and 21 months for stereotactic body radiotherapy.ResultsLate genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified.ConclusionDespite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.     

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

PURPOSE: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. METHODS AND MATERIALS: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. RESULTS: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. CONCLUSION: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.     

Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification

PurposeData for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control.Materials and methodsForty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4.ResultsAt a median follow-up of 18 months (range: 3–78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%.ConclusionsSalvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.     

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.     

Evaluation of tolerance and toxicity of high-dose-rate brachytherapy boost combined with interstitial hyperthermia for prostate cancer

Purpose The aim of this retrospective study was to evaluate the tolerance and early as well as late toxicity of high dose rate brachytherapy (HDRBT) boost combined with interstitial hyperthermia (IHT) in patients treated for prostate cancer.

Material and methods Between January 2011 and June 2013 76 patients diagnosed with prostate cancer received treatment consisting of external beam radiotherapy (EBRT), followed by a HDRBT boost combined with IHT. IHT was performed before each brachytherapy fraction.

Results The median follow-up time was 26.3 months (range 7–43 months). Early genitourinary (GU) grade 1 and 2 toxicities were common, but only two patients (2.6%) experienced acute urinary retention requiring temporary catheterisation (grade 2 toxicity). No grade 3 or 4 genitourinary or gastrointestinal toxicities were observed. In the group analysed, 59 of 76 patients had follow-up times longer than 18 months. The incidence of grade 2 late toxicity in the group studied did not exceed 23.7%. There were no late grade 2 or higher complications from the gastrointestinal tract.

Conclusions The tolerance of HDRBT boost combined with IHT is good. The profile and the percentage of early and late complications are acceptable.     

Salvage Re-irradiation With Single-modality Interstitial Brachytherapy for the Treatment of Recurrent Gynaecological Tumours in the Pelvis: A Multi-institutional Study

AimsRecurrent gynaecological tumours can cause significant morbidity with limited salvage options. This study investigates the strategy of salvage single-modality interstitial brachytherapy (SM-ISBT) for recurrent gynaecological pelvic cancer at two specialised ISBT centres.Materials and methodsPatients who had received salvage SM-ISBT for pelvic recurrence of gynaecological cancers from September 2008 to January 2017 were included. None had distant metastasis at the time of recurrence. Local control, progression-free and overall survival and long-term toxicities were evaluated.ResultsTwenty-six patients with a median follow-up of 24 months (range 2.5–106.3 months) after SM-ISBT were included. Primary cancer sites were endometrium (20), cervix (4), vulva (1) and vagina (1). All patients had prior whole-pelvic external beam irradiation and 16 had prior brachytherapy. The median disease-free survival prior to SM-ISBT was 20.3 months (interquartile range 9.9–30.5). SM-ISBT was delivered with high dose rate technique over three to six fractions. The median high-risk clinical target volume was 34.6 cm³, with a median D90 of 29.1 Gy (range 16.1–64.6). The median bladder, rectum and sigmoid D2cm³ were 15.5, 18.7 and 3.7 Gy, respectively. After SM-ISBT, complete and partial responses were achieved in 17 (64%) and 5 (19%) patients, respectively. Two (7.4%) patients had grade 3 toxicities (both vaginal stenosis), with no grade 4 complications. Eighteen patients (69%) recurred, including local, regional and metastatic in 14 (54%), 8 (30%) and 5 (19%) patients, respectively. Two-year local control, progression-free survival and overall survival were 50, 38 and 78%, respectively. In follow-up, 12 patients (46%) remained in local control.ConclusionsSalvage SM-ISBT re-irradiation for pelvic recurrence of gynaecological malignancies was feasible and safe. With limited salvage options, the local control obtained in more than a quarter of patients seems reasonable. Further efforts are needed to establish a consensus about the optimal patient selection, dose fractionation, implant technique and combination with systemic therapies.     

Perineural invasion on prostate needle biopsy does not predict biochemical failure following brachytherapy for prostate cancer

PURPOSE: To determine if the presence of perineural invasion (PNI) predicts biochemical recurrence in patients who underwent low-dose-rate brachytherapy for the treatment of localized prostate cancer. METHODS AND MATERIALS: A retrospective case control matching study was performed. The records of 651 patients treated with brachytherapy between 1996 and 2003 were reviewed. Sixty-three of these patients developed biochemical failure. These sixty-three patients were then matched in a one-to-one ratio to patients without biochemical failure, controlling for biopsy Gleason score, clinical stage, initial prostate-specific antigen, age, and the use of androgen deprivation. The pathology of the entire cohort was then reviewed for evidence of perineural invasion on initial prostate biopsy specimens. The biochemical relapse free survival rates for these two groups were compared. RESULTS: Cases and controls were well matched, and there were no significant differences between the two groups in age, Gleason grade, clinical stage, initial prostate-specific antigen, and the use of androgen deprivation. PNI was found in 19 (17%) patients. There was no significant difference in the rates of PNI between cases and controls, 19.6% and 14.3% respectively (p = 0.45). PNI did not correlate with biochemical relapse free survival (p = 0.40). CONCLUSION: Perineural invasion is not a significant predictor of biochemical recurrence in patients undergoing brachytherapy for prostate cancer.     

Low-Dose Adjuvant Cylinder Brachytherapy for Endometrioid Endometrial Cancer

PurposeOur purpose was to evaluate outcomes and sites of failure for women with early stage endometrial adenocarcinoma treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) with a low dose scheme.Methods and MaterialsRetrospective review identified 318 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrioid endometrial cancer who received adjuvant HDR VB to a dose of 24 Gray (Gy) in 6 fractions from 2005 to 2017. Patients with <6 months follow-up were excluded. Dose was prescribed to cylinder surface and computerized tomography (CT) imaging was performed before each fraction to assess cylinder placement. Rates of vaginal relapse (VR), pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were calculated by Kaplan-Meier method. Univariate analysis was performed by log rank test or Cox proportional hazards. Pretreatment CT images were analyzed for patients with VR.ResultsMedian follow-up was 42 months for 243 patients. The 3-year rates of VR, pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were 1.9%, 1.5%, 4.3%, 94.1%, and 98.9%, respectively. The 3-year VR rates by Gynecologic Oncology (GOG)-99 risk groups were 0%, 1.4%, and 3.2% for low risk, low-intermediate risk, and high-intermediate risk (HIR) disease (P = .5). By Post-operative Radiation Therapy in Endometrial Carcinoma (PORTEC) risk stratification, 3-year VR rate was 1.3% for HIR disease. On review of pretreatment CT images of the 6 patients with VR, 3 patients had relapse at the introitus outside of the treated vaginal length, and 3 had in-field recurrence at the vaginal apex. Higher body mass index (BMI) was associated with VR, with a 14% increase in risk per BMI unit (kg/m², P = .02). There were no reported grade 2 GI or any grade 3 toxicities.ConclusionsAdjuvant HDR VB with a low-dose regimen results in excellent clinical outcomes for patients with early stage endometrioid endometrial cancer. Patients with higher BMI may be at increased risk of VR, and additional study is needed to optimize brachytherapy treatment parameters.     

Moderately Hypofractionated Radiotherapy and Androgen Deprivation Therapy for High-risk Localised Prostate Cancer: Predictors of Long-term Biochemical Control and Toxicity

AimsThere is a paucity of long-term data on outcomes of high-risk prostatic adenocarcinoma after moderately hypofractionated radiotherapy with elective nodal treatment and long-term androgen deprivation therapy (ADT). We report long-term control and toxicity outcomes and analyse the predictors of failure and toxicity.Materials and methodsThe records of 120 consecutive high-risk prostate cancer patients treated in a single institution between February 2012 and December 2016 were retrospectively analysed. A moderately hypofractionted radiotherapy (HypoRT) regimen of 60 Gy in 20 fractions over 4 weeks with simultaneous elective pelvic irradiation to 44 Gy in 20 fractions with intensity-modulated radiotherapy was used, together with long-term ADT with either orchiectomy or medical castration for a total duration of 2–3 years. We analysed biochemical control, metastasis-free survival and late toxicities and their predictive factors using survival analysis.ResultsPatients had locally advanced cancers (cT3 77.5%, median pretreatment prostate-specific antigen 30 ng/ml, Gleason score 8–10 in 45.8%). The median follow-up time was 70 months. The 3- and 5-year probability of freedom from biochemical progression was 93% and 80%, respectively. The 5-year probability of freedom from local relapse/intra-pelvic nodal relapse/distant metastases as the site of first failure was 96%/97%/86%, respectively. Gleason score 8–10 and medical ADT for 2–3 years (as opposed to orchidectomy) were independent risk factors for distant metastases. A total of 18 grade 2 and above late gastrointestinal toxicity events and a total of 23 grade 2 and above late genitourinary toxicity events were documented. Patients who underwent a transurethral resection of prostate prior to radiotherapy had worse urological toxicity.ConclusionsHypoRT with elective nodal treatment results in excellent pelvic control. Distant metastases are the primary mode of failure. Risk of metastases is associated with Gleason score and the duration of ADT. Late urinary toxicities are more common in those with prior transurethral resection of prostate.     

Prognostic Factors in Postoperative Radiotherapy for Prostate Cancer – Tertiary Center Experience

BackgroundThe aim of the study was to analyse the prognostic factors in postoperative prostate cancer irradiation and develop a nomogram for disease-free survival (DFS).Patients and methodsThis retrospective study included 236 consecutive prostate cancer patients who had radical prostatectomy followed by radiotherapy (RT) at a single tertiary institution between 2009 and 2014. The main outcome was DFS analysed through uni- and multivariable analysis, Kaplan-Meier curves, log-rank testing, recursive partitioning analysis, and nomogram development.ResultsThe median follow up was 62.3 (interquartile range [IQR] 38.1–79) months. The independent clinical factors associated with increased risk of recurrence or progression in the multivariate analysis (MVA) were prostate-specific antigen (PSA) level before RT, pT3 characteristic, and local failure as salvage indication. The value of PSA nadir had a significant impact on the risk of biochemical failure. Biochemical control and DFS were significantly different depending on treatment indication (p < 0.0001). The recursive partitioning analysis highlighted the importance of the PSA level before RT, Gleason Grade Group, PSA nadir, and local failure as a treatment indication. Finally, the nomogram for DFS was developed and is available online at https://apps.konsta.com.pl/app/prostate-salvage-dfs/.ConclusionsThe Pre-RT PSA level, pT3 characteristic and local failure as salvage indication are pivotal prognostic factors associated with increased risk of recurrence or progression. The Gleason grade group of 4–5 and PSA nadir value allow for further risk stratification. The treatment outcomes in postoperative prostate cancer irradiation are significantly different depending on treatment indication. An online nomogram comprising of both pre-treatment and current data was developed allowing for visualization of changes in prognosis depending on clinical data.Key words: prostate cancer, prognostic factors, postoperative radiotherapy, nomogram, disease-free survival     

Salvage hypofractionated radiotherapy for biochemically recurrent prostate cancer after radical prostatectomy

PURPOSE: To evaluate whether hypofractionation is well tolerated and to preliminarily assess biochemical control of this regimen in a postprostatectomy, salvage setting. METHODS AND MATERIALS: A retrospective analysis was performed in 50 patients treated between May 2003 and December 2005 with hypofractionated radiotherapy for biochemical recurrence after radical prostatectomy. Radiotherapy was prescribed to the prostatic fossa to 65-70 Gy in 26-28 fractions of 2.5 Gy each, using intensity-modulated radiotherapy with daily image localization. Toxicities were scored using a modified Radiation Therapy Oncology Group scale and the Fox Chase modification of Late Effects Normal Tissue scale. The median follow-up was 18.9 months (range, 5.3-35.9). RESULTS: No Grade 3 or greater acute or late toxicities were observed. Grade 2 toxicities included four acute genitourinary, one acute gastrointestinal, two late genitourinary, and two late gastrointestinal toxicities. Of the 50 patients, 39 demonstrated a continuous biochemical response after salvage therapy, 3 had an initial response before prostate-specific antigen failure, and 7 had prostate-specific antigen progression, 1 of whom died of progressive metastatic disease. Finally, 1 patient discontinued therapy because of the diagnosis of a metachronous pancreatic cancer and died without additional prostate cancer follow-up. All remaining patients were alive at the last follow-up visit. A lower presalvage prostate-specific antigen level was the only significant prognostic factor for improved biochemical control. The estimated actuarial biochemical control rate at 2 years was 72.9%. CONCLUSIONS: The toxicity and early biochemical response rates were consistent with expectations from conventional fractionation. Additional follow-up is required to better document the biochemical control, but these results suggest that hypofractionation is a well-tolerated approach for salvage radiotherapy.     

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer.

PURPOSE: To evaluate treatment outcome of 3D conformal high dose rate (HDR) brachytherapy and external beam irradiation (EBRT) combined with temporary androgen deprivation for patients with localized prostate cancer. PATIENTS AND METHODS: Between January 1997 and September 1999 we treated 102 patients with stage T1-3 N0 M0 prostate cancer. Stage T1-2 was found in 71, T3 in 31 patients. Median pretreatment PSA level was 15.3 ng/ml. After ultrasound-guided transrectal implantation of four afterloading needles, CT based 3D brachytherapy planning was performed. All patients received four HDR implants using a reference dose per implant of 5 or 7Gy. Time between each implant was 14 days. After brachytherapy EBRT followed up to 39.6 or 45.0 Gy. All patients received temporary androgen deprivation, starting 2-19 months before brachytherapy, ending 3 months after EBRT. RESULTS: Median follow-up was 2.6 years (range 2.0-4.1 years). Actuarial biochemical control rate was 87% at 2 years and 82% at 3 years. In 14 patients we noted biochemical failure, in five patients clinical failure. Overall survival was 90%, disease specific survival 98.0% at 3 years. Acute grade 3 toxicity occurred in 4%, late grade 3 toxicity in 5%. One patient developed a prostatourethral-rectal fistula as late grade 4 toxicity. The conformal quality of 300 HDR implants was analyzed using dose volume histograms. CONCLUSIONS: 3D conformal HDR brachytherapy and EBRT combined with temporary androgen deprivation is an effective treatment modality for prostate cancer with minimal associated toxicity and encouraging biochemical control rates after a median follow-up of 2.6 years.     

Intensity Modulated Radiotherapy (IMRT) in the postoperative treatment of an adenocarcinoma of the endometrium complicated by a pelvic kidney

Purpose

To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost.

Materials and methods

Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml.

Results

Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6.

Conclusion

We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.     

Four-year biochemical outcome after radioimmunoguided transperineal brachytherapy for patients with prostate adenocarcinoma

PURPOSE: To evaluate 4-year biochemical outcomes for patients with prostate adenocarcinoma who underwent radioimmunoguided (Prostascint) permanent prostate brachytherapy. METHODS AND MATERIALS: Eighty patients with clinical T1C-T3A NxM0 prostate cancer underwent ProstaScint-guided prostate brachytherapy using either (103)Pd or (125)I between February 1997 and December 2000. Sixty-seven patients underwent prostate brachytherapy alone, whereas 13 patients received neoadjuvant hormonal manipulation before implantation. Risk factors (RF) included PSA >10, Stage >or=T2b, and Gleason grade >or=7. Sixty patients had low-risk disease (0 RF), 17 were intermediate risk (1 RF), and 3 were high risk (2 RF). Biochemical disease-free survival (bDFS) was calculated using the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria, a PSA cutoff of 1.0 ng/mL, and a PSA cutoff of 0.5 ng/mL. RESULTS: Four-year bDFS for the entire cohort was 97.4% using the ASTRO consensus criteria. Low-risk patients (60) had a 4-year bDFS of 100%; intermediate- and high-risk patients (20 patients) were 89.2%. The hormonally na?ve group (67 patients) had a 4-year bDFS of 96.9% and a median PSA nadir of 0.2 ng/mL. Median time to nadir was 19.8 months (range: 1.9-53.2 months). For the neoadjuvant hormonal therapy group (13 patients), ASTRO-defined bDFS was 100%. Overall, 85.2% of patients had a posttreatment PSA 相似文献   

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility,Tolerance and Outcome

AimsTo evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique.Materials and methodsBetween 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0–50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system.ResultsAll patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049).ConclusionsThe use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.