Salvage local treatment for localized radio-recurrent prostate cancer: a narrative review and future perspectives.

Although dose escalation protocols have improved biochemical control in prostate cancer radiotherapy, 10-45% of patients will experience disease recurrence. The prostate and seminal vesicles are the most frequent site of the first relapse. Traditionally, these patients have been managed with hormonal therapy, which is not curative. Recent improvements in diagnostic tests (e.g., multiparametric magnetic resonance and molecular imaging, including PET/CT scan with choline or Ga-PSMA) and new treatment techniques (e.g., stereotactic body radiation therapy or other minimally invasive alternatives like high-intensity focus ultrasound, cryoablation or high-dose-rate brachytherapy) offer new therapeutic strategies with the potential to cure some patients with limited adverse effects. In this narrative review, the authors present the most recent evidence to help identify the most suitable candidates for salvage treatment.

Linac-based SBRT as a feasible salvage option for local recurrences in previously irradiated prostate cancer.

BACKGROUND AND OBJECTIVE: The optimal management of prostate cancer (PC) recurrences after definitive or postoperative radiotherapy (RT) is still controversial. The aim of the present retrospective study was to report the preliminary clinical results and toxicity of a mono-institutional series of patients re-irradiated with linac-based SBRT in recurrent prostate cancer. METHODS: Inclusion criteria were previous definitive or adjuvant/salvage RT, evidence of biochemical recurrence and radiological detection of local relapse (Magnetic Resonance Imaging or PSMA/choline-Positron Emission Tomography), and IPSS <10. Toxicity was assessed according to Common Terminology Criteria for Adverse Events v4.0. RESULTS: Between 12/2014 and 12/2019, 24 patients with median age 75 years (65-89) underwent re-RT for PC recurrence. Median follow-up was 21 months (2-68). The recurrences occurred in 13 cases within the prostate and in 11 cases within the prostate bed. All patients were treated with SBRT to a median total dose of 30 Gy (25-36 Gy) in 5-6 fractions, and simultaneous androgen deprivation therapy was administered in 4 patients. Acute toxicity was G1 in 8.3% and G2 in 12.5% for genitourinary (GU), no acute gastrointestinal (GI) toxicity occurred. Concerning late side effects, 19.7% of patients were found to have ≥G2 GU toxicity, including one G3 urethral stenosis. Only one case of G1 late GI toxicity occurred and no ≥G2. The 2­year overall survival was 95%. The 1­ and 2­year biochemical relapse-free survival (BRFS) and progression-free survival (PFS) rates were 80 and 54.9%, respectively. CONCLUSION: Despite of the heterogeneity of the sample, linac-based SBRT as a salvage treatment in previously irradiated locally recurrent PC patients seems to be a safe and feasible treatment option. Long-term data are pending.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

AIM: To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). MATERIALS AND METHODS: 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT. RESULTS: Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). CONCLUSIONS: Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

Sequential boost in neoadjuvant irradiation for T3N0-1 rectal cancer: long-term results from a single-center experience.

PURPOSE: To evaluate the influence of radiation dose on tumor regression grade (TRG) and sphincter preservation rate in a series of cT3N0-1 rectal cancer patients treated with neoadjuvant chemoradiotherapy (CT-RT) with or without a sequential radiation boost. MATERIALS AND METHODS: Between May 2002 and September 2013, 116 cases were eligible for retrospective evaluation. Radiotherapy was delivered for a total dose of 45 Gy (no boost arm) or 50.4 Gy (boost arm). TRG was evaluated with the Dworak scale. RESULTS: Median follow-up was 62 months (range, 12-138 months). The 5-year overall survival and local control rates were 72% and 93%, respectively. Fifty-five patients (47%) were treated with a sequential radiation boost and 61 (53%) without a boost. Eighty patients (72%) presented T3N0 disease and 32 (28%) T3N1 disease. Concomitant capecitabine was administered in 92 cases (79%) and intravenous 5-fluorouracil in 24 cases (21%). Sphincter preservation was performed in 82% of patients in the boost arm and 66% in the no-boost arm. A higher TRG was related to a longer interval between neoadjuvant treatment and surgery (p<0.001). The probability of a TRG ≥2 was 2.5 times higher in the boost arm. A gain in local control, estimated at 4% during the first 3 years after CT-RT, favored the boost arm. CONCLUSIONS: The long-term results from our single-center experience confirm literature data on the role of a sequential boost in tumor response after neoadjuvant CT-RT in a series of cT3N0-1 rectal cancer patients.

Impact of 18F-Choline PET/CT in the Decision-Making Strategy of Treatment Volumes in Definitive Prostate Cancer Volumetric Modulated Radiation Therapy.

INTRODUCTION: Aim of the study is to evaluate the impact of Cho-PET/CT in decision-making strategy of patients with localized prostate cancer (PC) eligible to definitive radiotherapy (RT). MATERIALS AND METHODS: Sixty patients Cho-PET/CT before RT were prospectively enrolled. All patients were treated with volumetric modulated arc therapy with simultaneous integrated boost in 28 fractions. Androgen deprivation therapy was prescribed according to National Comprehensive Cancer Network (NCCN) risk classification. Therapeutic strategy based on the Cho-PET/CT evaluation was compared with the strategy that would have been proposed in case of PET not available and/or not strictly indicated, according to international and national PC guidelines. RESULTS: Cho-PET/CT was positive in 57 cases (95%): T in 45 (79%); T in combination with N in 8 (14%); and M (bone) in combination with T or N, or both, in 4 (7%). After Cho-PET/CT, patients were stratified as follows: 26 (43%) low risk, 10 (16%) intermediate risk, and 24 (41%) high risk. Cho-PET/CT shifted treatment indication in 13 cases (21%). The changes regarding radiation treatment volumes were as follows: 6 intermediate risk (10%) shifted to high risk and consequently were irradiated on prostate, seminal vesicles, and pelvic nodes PTVs; in 7 high risk (11%), the Cho-PET/CT showed bone and/or N uptake, and consequently, a simultaneous integrated boost on PET positive sites was prescribed. CONCLUSIONS: Cho-PET/CT seems to be a promising diagnostic tool in patients who are candidates for radical RT and supporting the decision making in treatment planning, in particular in intermediate-high risk.

Volumetric-modulated arc therapy with vaginal cuff simultaneous integrated boost as an alternative to brachytherapy in adjuvant irradiation for endometrial cancer: a prospective study.

AIM: To report preliminary results of a prospective study using pelvic volumetric-modulated arc therapy and simultaneous integrated boost (SIB-VMAT) on vaginal cuff postoperatively in patients with endometrial cancer (EC). PATIENTS AND METHODS: Fifty consecutive patients, submitted surgery for EC, were recruited to SIB-VMAT prescribing a dose of 54 Gy to the pelvis and 66 Gy to the vaginal cuff in 30 fractions. A 2 mm transvaginal probe and magnetic resonance imaging were used to define the vaginal cuff. Toxicity data were collected according to Common Terminology Criteria for Adverse Events v4.0; clinical outcomes were analyzed. RESULTS: The median follow-up was 26 (range=12 to 39) months. According to International Federation of Gynecology and Obstetrics 2009, the stages were: IB1 in 20%, IB2 in 28%, IIA2 in 16%, IIB in 6%, IIIA in 2%, and IIIC in 28%. The 2-year Overall Survival and Local Control were 96% and 100%, respectively. Two pelvic node failures were registered. Acute gastrointestinal toxicity was: G0 in 12%, G1 in 52%, G2 in 36%; no case of toxicity G3 or more was observed. Acute genitourinary toxicity was: G0 in 10%, G1 in 42%, G2 in 48%; no case of toxicity G3 or more was observed. No late severe gastrointestinal or genitourinary toxicities were reported. A statistical correlation was found between acute G2 gastrointestinal toxicity with bowel V20 Gy ≥ 30%, V20 ≥ 40%, V30 ≥ 30%, Dmax ≥ 45 Gy. Acute G2 genitourinary toxicity was threefold higher with chemotherapy. CONCLUSION: In patients with EC, SIB-VMAT is feasible, and well tolerated. Preliminary data of clinical outcome are promising. Further prospective studies are advocated.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

Physics aspects of prostate tomotherapy: planning optimization and image-guidance issues.

PURPOSE: To review planning and image-guidance aspects of more than 3 years experience in the treatment of prostate cancer with Helical Tomotherapy (HT). METHODS AND MATERIALS: Planning issues concerning two Phase I-II clinical studies were addressed: in the first one, 58 Gy in 20 fractions were delivered to the prostatic bed for post-prostatectomy patients: in the second one, a simultaneous integrated boost (SIB) approach was applied for radical treatment, delivering 71.4-74.2 Gy to the prostate in 28 fractions. On-line daily MVCT image guidance was applied: bone match was used for post-operative patients while prostate match was applied for radically treated patients. MVCT data of a large sample of both categories of patients were reviewed. RESULTS: At now, more than 250 patients were treated. Planning data show the ability of HT in creating highly homogeneous dose distributions within PTVs. Organs at risk (OAR) sparing also showed to be excellent. HT was also found to favorably compare to inversely-optimized IMAT in terms of PTVs coverage and dose distribution homogeneity. In the case of pelvic nodes irradiation, a large sparing of bowel was evident compared to 3DCRT and conventional 5-fields IMRT. The analysis of MVCT data showed a limited motion of the prostate (about 5% of the fractions show a deviation > or =3 mm in posterior-anterior direction), due to the careful application of rectal emptying procedures. Based on phantom measurements and on the comparison with intra-prostatic calcification-based match, direct visualization prostate match seems to be sufficiently reliable in assessing shifts > or =3 mm. CONCLUSIONS: HT offers excellent planning solutions for prostate cancer, showing to be highly efficient in a SIB scenario. Daily MVCT information showed evidence of a limited motion of the prostate in the context of rectal filling control obtained by instructing patients in self-administrating a rectal enema.

Evidence of limited motion of the prostate by carefully emptying the rectum as assessed by daily MVCT image guidance with helical tomotherapy.

PURPOSE: To assess setup and organ motion error by means of analysis of daily megavoltage computed tomography (MVCT) of patients treated with hypofractionated helical tomotherapy (71.4-74.2 Gy in 28 fractions). METHODS AND MATERIALS: Data from 21 patients were analyzed. Patients were instructed to empty the rectum carefully before planning CT and every morning before therapy by means of a self-applied rectal enema. The position of the prostate was assessed by means of automatic bone matching (BM) with the planning kilovoltage CT (BM, setup error) followed by a direct visualization (DV) match on the prostate. Deviations between planning and therapy positions referred to BM and BM + DV were registered for the three main axes. In case of a full rectum at MVCT with evident shift of the prostate, treatment was postponed until after additional rectal emptying procedures; in this case, additional MVCT was performed before delivering the treatment. Data for 522 fractions were available; the impact of post-MVCT procedure was investigated for 17 of 21 patients (410 fractions). RESULTS: Prostate motion relative to bony anatomy was limited. Concerning posterior-anterior shifts, only 4.9% and 2.7% of fractions showed deviation of 3 mm or greater of the prostate relative to BM without and with consideration of post-MVCT procedures, respectively. Interobserver variability for BM + DV match was within 0.8 mm (1 SD). CONCLUSIONS: Daily MVCT-based correction is feasible. The BM + DV matching was found to be consistent between operators. Rectal emptying using a daily enema is an efficient tool to minimize prostate motion, even for centers that have not yet implemented image-guided radiotherapy.