Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

BACKGROUND: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. METHODS: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. RESULTS: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging.

PURPOSE: We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. MATERIALS AND METHODS: After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. RESULTS: A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92-17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90-21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. CONCLUSIONS: The combination of 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

Contemporary Mapping of Post-Prostatectomy Prostate Cancer Relapse with 11C-Choline Positron Emission Tomography and Multiparametric Magnetic Resonance Imaging.

PURPOSE: We identify sites and patterns of cancer recurrence in patients with post-prostatectomy biochemical relapse using 11C-choline positron emission tomography/computerized tomography and endorectal coil multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Between January 2008 and June 2015, 2,466 men underwent choline positron emission tomography for suspected prostate cancer relapse at our institution. Of these men 202 did not receive hormone or radiation therapy, underwent imaging with choline positron emission tomography and multiparametric magnetic resonance imaging, and were found to have disease recurrence. Overall patterns of recurrence were described, and factors associated with local only recurrence were evaluated using univariable and multivariable logistic regression. RESULTS: Median prostate specific antigen at positive scan was 2.3 ng/ml (IQR 1.4-5.5) with a median time from prostate specific antigen relapse to lesion visualization of 15 months (IQR 4.8-34.2). Of these 202 men 68 (33%) exhibited local only, 45 (22%) local plus metastatic and 89 (45%) metastatic only relapse. Pelvic node only relapse was observed in 39 (19%) men. Median prostate specific antigen at positive imaging for patients with local only, metastatic only and local plus metastatic relapse was 2.3, 2.7 and 2.2 ng/ml (p=0.46), with a median interval from biochemical recurrence to positive scan of 33.5, 7.0 and 15.0 months, respectively (p <0.001). On multivariable analysis time from biochemical recurrence to positive imaging was independently associated with local only recurrence (OR 1.10 for every 6-month increase, p=0.012). CONCLUSIONS: Combined choline positron emission tomography and multiparametric magnetic resonance imaging evaluation of biochemical recurrence after prostatectomy reveals an anatomically diverse pattern of recurrence. These findings have implications for optimizing the salvage treatment of patients with prostate cancer with relapse following surgery.

Prostate Cancer Lung Metastasis: Clinical Insights and Therapeutic Strategies.

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. METHODS: We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. RESULTS: We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21-0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09-0.87, p = 0.0325). CONCLUSION: PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

11C-choline positron emission tomography/computed tomography for detection of disease relapse in patients with history of biochemically recurrent prostate cancer and prostate-specific antigen ≤0.1 ng/ml.

OBJECTIVES: The objective was to evaluate the diagnostic performance of surveillance11 C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml. MATERIALS AND METHODS: We included patients who had been treated for BCR PCa and had a surveillance11 C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression. RESULTS: In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing. CONCLUSIONS: Surveillance11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa.

A Rare Case of Prostate-Specific Antigen-Producing Metastatic Parotid Adenocarcinoma Developing Androgen Receptor Resistance.

A 62-year-old man presented with a rising serum concentration of prostate-specific antigen (PSA) to 53.3 ng/mL (to convert to µg/L, multiply by 1) and a PSA doubling time of 2.6 months. Computed tomography, fluorodeoxyglucose-positron emission tomography, and C-11 choline positron emission tomography demonstrated a parotid mass with innumerable lytic bone lesions and diffuse metastatic disease to the neck and mediastinal lymph nodes. Mediastinal lymph node biopsy revealed salivary ductal adenocarcinoma that produced PSA and demonstrated androgen receptor sensitivity. The patient had a prolonged clinical benefit to first- and second-line hormone therapy, and his PSA levels correlated with treatment response, development of hormone resistance, and progression. In summary, urologists, pathologists, and primary care providers should be aware that a rising PSA level in the setting of a head and neck mass in a patient without a history of prostate cancer does not constitute a diagnosis of metastatic prostate adenocarcinoma and that other primary tumors should be considered and a broader imaging and pathologic evaluation is indicated.

11C-Choline PET Guided Salvage Radiation Therapy for Isolated Pelvic and Paraortic Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Rationale and Early Genitourinary or Gastrointestinal Toxicities.

PURPOSE: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of 11C-choline-positron emission tomography (CholPET) guided lymph node (LN) radiation therapy (RT) in patients who experience biochemical failure after radical prostatectomy. METHODS AND MATERIALS: From 2013 to 2016, 107 patients experienced biochemical failure of prostate cancer, had CholPET-detected pelvic and/or paraortic LN recurrence, and were referred for RT. Patients received androgen suppression and CholPET guided LN RT (median dose, 45 Gy) with a simultaneous integrated boost to CholPET-avid sites (median dose, 56.25 Gy), all in 25 fractions. RT-naïve patients had the prostatic fossa included in the initial treatment volumes followed by a sequential boost (median dose, 68 Gy). GI and GU AEs were reported per Common Terminology Criteria for Adverse Events (version 4.0) with data gathered retrospectively. Differences in maximum GI and GU AEs at baseline, immediately post-RT, and at early (median, 4 months) and late (median, 14 months) follow-up were assessed. RESULTS: Median follow-up was 16 months (interquartile range [IQR], 11-25). Median prostate-specific antigen at time of positive CholPET was 2.3 ng/mL (IQR, 1.3-4.8), with a median of 2 (IQR, 1-4) choline-avid LNs per patient. Most recurrences were within the pelvis (53%) or pelvis + paraortic (40%). Baseline rates of grade 1 to 2 GI AEs were 8.4% compared with 51.9% (4.7% grade 2) of patients post-RT (P < .01). These differences resolved by 4-month (12.2%, P = .65) and 14-month AE assessments (9.1%, P = .87). There was no significant change in grade 1 to 2 GU AEs post-RT (64.1%) relative to baseline (56.0%, P = .21), although differences did arise at 4-month (72.2%, P = .01) and 14-month (74.3%, P = .01) AE assessments. CONCLUSIONS: Salvage CholPET guided nodal RT has acceptably low rates of acute GI and GU AEs and no significant detriment in 14-month GI AEs. These data are of value in counseling patients and designing prospective trials evaluating the oncologic efficacy of this treatment strategy.

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease.

BACKGROUND: Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE: To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION: C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS: Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS: CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY: We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.